CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.
CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.
Chemokine receptors that are specific for CXC CHEMOKINES.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and T-LYMPHOCYTES. These receptors also bind several other CXC CHEMOKINES.
Group of chemokines with paired cysteines separated by a different amino acid. CXC chemokines are chemoattractants for neutrophils but not monocytes.
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and BASOPHILS.
Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.
A CXC chemokine that is induced by GAMMA-INTERFERON. It is a chemotactic factor for activated T-LYMPHOCYTES and has specificity for the CXCR3 RECEPTOR.
A CXC chemokine that is induced by GAMMA-INTERFERON and is chemotactic for MONOCYTES and T-LYMPHOCYTES. It has specificity for the CXCR3 RECEPTOR.
An INTEFERON-inducible CXC chemokine that is specific for the CXCR3 RECEPTOR.
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
A CXC chemokine that has stimulatory and chemotactic activities towards NEUTROPHILS. It has specificity for CXCR1 RECEPTORS and CXCR2 RECEPTORS.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A CXC chemokine with specificity for CXCR2 RECEPTORS. It has growth factor activities and is implicated as a oncogenic factor in several tumor types.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
CCR receptors with specificity for CHEMOKINE CCL19 and CHEMOKINE CCL21. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
CCR receptors with specificity for CHEMOKINE CCL17 and CHEMOKINE CCL22. They are expressed at high levels in T-LYMPHOCYTES; MAST CELLS; DENDRITIC CELLS; and NK CELLS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Benign epidermal proliferations or tumors; some are viral in origin.
A cell line derived from cultured tumor cells.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Cellular receptors that bind the human immunodeficiency virus that causes AIDS. Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120.
Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
CCR receptors with specificity for CHEMOKINE CCL3; CHEMOKINE CCL4; and CHEMOKINE CCL5. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; MAST CELLS; and NK CELLS. The CCR5 receptor is used by the HUMAN IMMUNODEFICIENCY VIRUS to infect cells.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Established cell cultures that have the potential to propagate indefinitely.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
A CXC chemokine that is predominantly expressed in EPITHELIAL CELLS. It has specificity for the CXCR2 RECEPTORS and is involved in the recruitment and activation of NEUTROPHILS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.
A species of LENTIVIRUS, subgenus feline lentiviruses (LENTIVIRUSES, FELINE) isolated from cats with a chronic wasting syndrome, presumed to be immune deficiency. There are 3 strains: Petaluma (FIP-P), Oma (FIP-O) and Puma lentivirus (PLV). There is no antigenic relationship between FIV and HIV, nor does FIV grow in human T-cells.
External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.
Aquatic vertebrate sensory system in fish and amphibians. It is composed of sense organs (canal organs and pit organs) containing neuromasts (MECHANORECEPTORS) that detect water displacement caused by moving objects.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.
Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.
A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards DENDRITIC CELLS and T-LYMPHOCYTES.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
Adherence of cells to surfaces or to other cells.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils.
Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Cell surface proteins that bind interleukins and trigger intracellular changes influencing the behavior of cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Progenitor cells from which all blood cells derive.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.

Phenotypic and functional evidence for the expression of CXCR4 receptor during megakaryocytopoiesis. (1/2860)

The identification of stromal cell-derived factor (SDF)-1alpha as a chemoattractant for human progenitor cells suggests that this chemokine and its receptor might represent critical determinants for the homing, retention, and exit of precursor cells from hematopoietic organs. In this study, we investigated the expression profile of CXCR4 receptor and the biological activity of SDF-1alpha during megakaryocytopoiesis. CD34(+) cells from bone marrow and cord blood were purified and induced to differentiate toward the megakaryocyte lineage by a combination of stem-cell factor (SCF) and recombinant human pegylated megakaryocyte growth and development factor (PEG-rhuMGDF). After 6 days of culture, a time where mature and immature megakaryocytes were present, CD41(+) cells were immunopurified and CXCR4mRNA expression was studied. High transcript levels were detected by a RNase protection assay in cultured megakaryocytes derived from cord blood CD34(+) cells as well as in peripheral blood platelets. The transcript levels were about equivalent to that found in activated T cells. By flow cytometry, a large fraction (ranging from 30% to 100%) of CD41(+) cells showed high levels of CXCR4 antigen on their surface, its expression increasing in parallel with the CD41 antigen during megakaryocytic differentiation. CXCR4 protein was also detected on peripheral blood platelets. SDF-1alpha acts on megakaryocytes by inducing intracellular calcium mobilization and actin polymerization. In addition, in in vitro transmigration experiments, a significant proportion of megakaryocytes was observed to respond to this chemokine. This cell migration was inhibited by pertussis toxin, indicating coupling of this signal to heterotrimeric guanine nucleotide binding proteins. Although a close correlation between CD41a and CXCR4 expession was observed, cell surface markers as well as morphological criteria indicate a preferential attraction of immature megakaryocytes (low level of CD41a and CD42a), suggesting that SDF-1alpha is a potent attractant for immature megakaryocytic cells but is less active on fully mature megakaryocytes. This hypothesis was further supported by the observation that SDF-1alpha induced the migration of colony forming unit-megakaryocyte progenitors (CFU-MK) and the expression of activation-dependent P-selectin (CD62P) surface antigen on early megakaryocytes, although no effect was observed on mature megakaryocytes and platelets. These results indicate that CXCR4 is expressed by human megakaryocytes and platelets. Furthermore, based on the lower responses of mature megakaryocytes and platelets to SDF-1alpha as compared with early precursors, these data suggest a role for this chemokine in the maintenance and homing during early stages of megakaryocyte development. Moreover, because megakaryocytes are also reported to express CD4, it becomes important to reevaluate the role of direct infection of these cells by the human immunodeficiency virus (HIV)-1 in HIV-1-related thrombocytopenia.  (+info)

Interactions between Tat and TAR and human immunodeficiency virus replication are facilitated by human cyclin T1 but not cyclins T2a or T2b. (2/2860)

The transcriptional transactivator (Tat) from the human immunodeficiency virus (HIV) does not function efficiently in Chinese hamster ovary (CHO) cells. Only somatic cell hybrids between CHO and human cells and CHO cells containing human chromosome 12 (CHO12) support high levels of Tat transactivation. This restriction was mapped to interactions between Tat and TAR. Recently, human cyclin T1 was found to increase the binding of Tat to TAR and levels of Tat transactivation in rodent cells. By combining individually with CDK9, cyclin T1 or related cyclins T2a and T2b form distinct positive transcription elongation factor b (P-TEFb) complexes. In this report, we found that of these three cyclins, only cyclin T1 is encoded on human chromosome 12 and is responsible for its effects in CHO cells. Moreover, only human cyclin T1, not mouse cyclin T1 or human cyclins T2a or T2b, supported interactions between Tat and TAR in vitro. Finally, after introducing appropriate receptors and human cyclin T1 into CHO cells, they became permissive for infection by and replication of HIV.  (+info)

Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. (3/2860)

To define predictors of survival time in late human immunodeficiency virus type 1 (HIV-1) disease, long- and short-duration survivors were studied after their CD4+ T cells fell to +info)

Effect of mutations in the second extracellular loop of CXCR4 on its utilization by human and feline immunodeficiency viruses. (4/2860)

CCR5 and CXCR4 are the principal CD4-associated coreceptors used by human immunodeficiency virus type 1 (HIV-1). CXCR4 is also a receptor for the feline immunodeficiency virus (FIV). The rat CXCR4 cannot mediate infection by HIV-1NDK or by FIVPET (both cell line-adapted strains) because of sequence differences with human CXCR4 in the second extracellular loop (ECL2). Here we made similar observations for HIV-189.6 (a strain also using CCR5) and for a primary HIV-1 isolate. It showed the role of ECL2 in the coreceptor activity of CXCR4 for different types of HIV-1 strains. By exchanging ECL2 residues between human and rat CXCR4, we found that several amino acid differences contributed to the inactivity of the rat CXCR4 toward HIV-189.6. In contrast, its inactivity toward HIV-1NDK seemed principally due to a serine at position 193 instead of to an aspartic acid (Asp193) in human CXCR4. Likewise, a mutation of Asp187 prevented usage of CXCR4 by FIVPET. Different mutations of Asp193, including its replacement by a glutamic acid, markedly reduced or suppressed the activity of CXCR4 for HIV-1NDK infection, indicating that the negative charge was not the only requirement. Mutations of Asp193 and of arginine residues (Arg183 and Arg188) of CXCR4 reduced the efficiency of HIV-1 infection for all HIV-1 strains tested. Other ECL2 mutations tested had strain-specific effects or no apparent effect on HIV-1 infection. The ECL2 mutants allowed us to identify residues contributing to the epitope of the 12G5 monoclonal antibody. Overall, residues with different charges and interspersed in ECL2 seem to participate in the coreceptor activity of CXCR4. This suggests that a conformational rather than linear epitope of ECL2 contributes to the HIV-1 binding site. However, certain HIV-1 and FIV strains seem to require the presence of a particular ECL2 residue.  (+info)

Identification of CXCR4 domains that support coreceptor and chemokine receptor functions. (5/2860)

The interaction of the chemokine stromal cell-derived factor 1 (SDF-1) with its receptor CXCR4 is vital for cell trafficking during development, is capable of inhibiting human immunodeficiency virus type 1 (HIV-1) utilization of CXCR4 as a coreceptor, and has been implicated in delaying disease progression to AIDS in vivo. Because of the importance of this chemokine-chemokine receptor pair to both development and disease, we investigated the molecular basis of the interaction between CXCR4 and its ligands SDF-1 and HIV-1 envelope. Using CXCR4 chimeras and mutants, we determined that SDF-1 requires the CXCR4 amino terminus for binding and activates downstream signaling pathways by interacting with the second extracellular loop of CXCR4. SDF-1-mediated activation of CXCR4 required the Asp-Arg-Tyr motif in the second intracellular loop of CXCR4, was pertussis toxin sensitive, and did not require the distal C-terminal tail of CXCR4. Several CXCR4 mutants that were not capable of binding SDF-1 or signaling still supported HIV-1 infection, indicating that the ability of CXCR4 to function as a coreceptor is independent of its ability to signal. Direct binding studies using the X4 gp120s HXB, BH8, and MN demonstrated the ability of HIV-1 gp120 to bind directly and specifically to the chemokine receptor CXCR4 in a CD4-dependent manner, using a conformationally complex structure on CXCR4. Several CXCR4 variants that did not support binding of soluble gp120 could still function as viral coreceptors, indicating that detectable binding of monomeric gp120 is not always predictive of coreceptor function.  (+info)

Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry? (6/2860)

Despite being able to use the Bonzo coreceptor as efficiently as CCR5 in transfected cells, pediatric human immunodeficiency virus type 1 isolate P6 was unable to replicate in peripheral blood mononuclear cells (PBMC) lacking the CCR5 receptor. Furthermore, its replication in wild-type PBMC was completely inhibited by inhibitors of CCR5-mediated entry. Similarly, maternal isolate M6 could use CCR5, CXCR4, Bonzo, and other coreceptors in transfected cells but was completely sensitive to inhibitors of CCR5- and CXCR4-mediated entry when grown in PBMC. The ability of these viruses to use coreceptors in addition to CCR5 and CXCR4 in vitro was, therefore, irrelevant to their drug sensitivity in primary cells. We argue that CCR5 and CXCR4 should remain the primary targets for antiviral drug development, pending strong evidence to the contrary.  (+info)

Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. (7/2860)

Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a principal HIV-1 coreceptor, is posttranslationally modified by O-linked glycosylation and by sulfation of its N-terminal tyrosines. Sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells expressing CCR5 and CD4. CXCR4, another important HIV-1 coreceptor, is also sulfated. Tyrosine sulfation may contribute to the natural function of many 7TMS receptors and may be a modification common to primate immunodeficiency virus coreceptors.  (+info)

Cofactors for human immunodeficiency virus entry into primary macrophages. (8/2860)

Macrophages are permissive for macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates that use CCR5 for entry but are resistant to CXCR-4-dependent T cell-tropic prototype strains. M-tropic variants are critical for HIV-1 transmission, and persons who are homozygous for an inactivating mutation of CCR5 are resistant to HIV-1 in vivo. In vitro, their macrophages and lymphocytes are resistant to M-tropic strains that depend on CCR5. It is shown that CCR5-deficient macrophages are permissive for a dual-tropic isolate, 89.6, that uses CCR5, CXCR-4, and other cofactors. Entry by 89.6 into CCR5-deficient macrophages was blocked by the CXCR-4 ligand SDF and by an anti-CXCR-4 antibody. Immunoflorescence staining and reverse transcription PCR confirmed macrophage CXCR-4 expression. Thus, CXCR-4 on macrophages mediates entry of certain dual-tropic but not T cell-tropic isolates. Therefore, HIV-1 strains differ in how they utilize chemokine receptors as cofactors for entry, and the ability of a chemokine receptor to facilitate entry depends on the cell in which it is expressed.  (+info)

[45 Pages Report] Check for Discount on C-X-C Chemokine Receptor Type 1 (CDw128a or High Affinity Interleukin 8 Receptor A or IL8 Receptor Type 1 or CD181 or CXCR1) - Pipeline Review, H2 2017 report by Global Markets Direct. According to the recently published report C-X-C Chemokine...
C-X-C Chemokine Receptor Type 2 (CDw128b or GRO/MGSA Receptor or High Affinity Interleukin 8 Receptor B or IL8 Receptor Type 2 or CD182 or CXCR2) - Pipeline Review, ...
Table of Contents. Table of Contents 2. List of Tables 6. List of Figures 6. Introduction 7. Global Markets Direct Report Coverage 7. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5) Overview 8. Therapeutics Development 9. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by Stage of Development 9. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by Therapy Area 10. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by Indication 11. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Pipeline Products Glance 12. Late Stage Products 12. Early Stage Products 13. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by ...
The chemokine receptors CXCR1-3 bind to 11 chemokines (CXCL1-11) that are clustered on the same chromosome in mammals but are largely missing in ray-finned fish. A second CXCR1/2, and a CXCR3a and CXCR3b gene have been cloned in rainbow trout. Analysis of CXCR1-R3 genes in lobe-finned fish, ray-finned fish and tetrapod genomes revealed that the teleostomian ancestor likely possessed loci containing both OCCR1 and CXCR2, and CXCR3a and CXCR3b. Based on this synteny analysis the first trout CXCR1/2 gene was renamed CXCR1, and the new gene CXCR2. The CXCR1/R2 locus was shown to have further expanded in ray-finned fish. In relation to CXCR3, mammals appear to have lost CXCR3b and birds both CXCR3a and CXCR3b during evolution. Trout CXCR1-R3 have distinct tissue expression patterns and are differentially modulated by PAMPs, proinflammatory cytokines and infections. They are highly expressed in macrophages and neutrophils, with CXCR1 and CXCR2 also expressed in B-cells. (C) 2014 The Authors. Published ...
CXCR4 is the Gi protein-linked seven-transmembrane receptor for the alpha chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In
Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11. CXCR3 is expressed primarily on activated T lymphocytes and NK cells, and some epithelial cells. CXCR3 and CCR5 are preferentially expressed on Th1 cells, whereas Th2 cells favor the expression of CCR3 and CCR4. CXCR3 ligands that attract Th1 cells can concomitantly block the migration of Th2 cells in response to CCR3 ligands, thus enhancing the polarization of effector T cell recruitment. Binding of CXCL9, CXCL10, and CXCL11 to CXCR3 is able to elicit increases in intracellular Ca2++ levels and activate phosphoinositide 3-kinase and mitogen-activated ...
The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. This gene, IL8RB, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. [provided by RefSeq, Jul 2008 ...
The major goal of this study was to investigate the effect of severe sepsis on the expression and function of the two CXC chemokine receptors on circulating PMN. We found that CXCR2 expression was reduced by 50% in septic patients, whereas CXCR1 expression was preserved. Similarly, we found that the chemotactic responses to the CXC chemokines which bind with high affinity to only CXCR2 (GRO-α, -β, and -γ and ENA-78) were markedly suppressed in PMN from septic patients, whereas the chemotactic response to IL-8, which binds with high affinity to either CXCR, was preserved. Finally, specific blockade of CXCR1 had a more pronounced suppressive effect on the chemotactic function of PMN from septic patients than on that of PMN from normal donors. Taken together, these observations indicate that CXCR2 is functionally down-regulated in severe sepsis, leaving CXCR1 as the dominant receptor for mediating the effects of the CXC chemokines in PMN from these patients.. Previous reports 13, 21, 30 ...
Title:Structure-Based Development of Antagonists for Chemokine Receptor CXCR4. VOLUME: 9 ISSUE: 1. Author(s):Chongqian Zhang, Tingjun Hou, Zhiwei Feng and Youyong Li. Affiliation:Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.. Keywords:CXCR4, crystal structure, anti-HIV-1 inhibitors, DOCK, molecular dynamics, SAR, drug development, critical residues, chemokine receptor, antagonist. Abstract:The C-X-C chemokine receptor-4(CXCR4) is a G-protein coupled receptor (GPCR) which belongs to the family I GPCR or rhodopin-like GPCR family. CXCR4 plays a crucial role as a co-receptor with CCR5 for HIV-1 anchoring to mammalian cell membrane, and is implicated in cancer metastasis and inflammation. Recently, crystal structure of human CXCR4 receptor was reported, which facilitates the structure-based drug discovery of CXCR4 significantly. Here we summarize the structure ...
Oral squamous cell carcinoma (SCC) has a striking tendency to invade to bone. The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively secreted by osteoblasts and plays a key role in homing of hematopoietic cells to the bone marrow. Interleukin (IL)-6 plays an important role in osteoclastogenesis. Herein, we found that SDF-1α increased the secretion of IL-6 in cultured human SCC cells, as shown by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. SDF-1α also increased the surface expression of chemokine receptor 4 (CXCR4) in SCC cells. CXCR4-neutralizing antibody, CXCR4-specific inhibitor (AMD3100) or small interfering RNA against CXCR4 inhibited SDF-1α-induced increase IL-6 production. The transcriptional regulation of IL-6 by SDF-1α was mediated by phosphorylation of extracellular signal-regulated kinases (ERKs) and activation of the nuclear factor-kappa B (NF-κB) components p65 and p50. The binding of p65 and p50 to the NF-κB element on ...
Platelet-derived SDF-1α (stromal cell derived factor-α) mediates inflammation, immune defence and repair mechanisms at site of tissue injury. This review summarizes the relative expression of CXC chemokine receptor 4 (CXCR4) and CXCR7 in platelets, their dynamic trafficking in presence of ligands like chemokine C-X-C-motif ligand 11 (CXCL11), CXCL12 and MIF (macrophage migration inhibitory factor); how these receptors differentially mediate the functional and survival response to the chemokines CXCL11, CXCL12 and MIF. We further elaborate and emphasize the prognostic significance of platelet surface expression of CXCR4-CXCR7 in the context of coronary artery disease (CAD). SDF-1α/CXCL12, CXCL11, MIF effects mediated through CXCR4 and CXCR7 may play a regulatory role at the site of vascular and tissue inflammation, immune defence and repair where activated platelets reach as forerunners and function as critical players. ...
CXCR4 and CXCL12 have become a major avenue of cancer research since Muller and colleagues established a role for this chemokine receptor/ligand pair in cancer metastasis (22). CXCR4 is upregulated in at least 23 different cancers (3) and is associated with a clinical poor prognosis (23, 24). We reported that CXCR4 activation upregulates β1 integrin function in B16 melanoma cells, enhancing their ability to adhere to the vessel wall, and thereby increasing the risk for lung metastasis (5). Others reported that CXCR4-CXCL12 signaling also promotes lung metastasis through stromal cells (16, 25). For example, CXCR4 recruits myeloid dendritic cells, which enhance tumor growth, angiogenesis, and micrometastasis (25). Mice with CXCR4+/− stromal cells exhibit diminished formation of CXCR4-expressing B16 lung metastasis (16). Administration of AMD3100 to CXCR4+/− mice further reduced tumor formation/growth (16), suggesting that inhibitors of CXCR4 not only control metastatic lung lesions directly, ...
CXCR4, (a CXC chemokine Receptor), also called fusin, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. This receptor is one of several chemokine receptors that HIV isolates can use to infect CD4+ T cells. Traditionally, HIV isolates that use CXCR4 are known as T-cell tropic isolates. Typically these viruses are found late in infection. It is unclear whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.. CXCR4 is upregulated during the implantation window in natural and Hormone Replacement Therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.. CXCR4s ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. ...
Clone REA649 recognizes the human CD184 antigen, a multi-pass membrane protein, also known as C-X-C chemokine receptor type 4 (CXCR4), leukocyte-derived seven transmembrane domain receptor (LESTR), or fusin. CD184 is ubiquitously expressed on blood and tissue cells. It mediates chemotaxis in mature and progenitor blood cells and is important for B lymphopoiesis, myelopoiesis, and cardiogenesis. CD184 exclusively interacts with the endogenous ligand CXCL12. Binding of CXCL12 transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Although CXCL12 is the only known chemokine that binds CD184, recent studies suggest that extracellular ubiquitin also acts as an immune modulator through CD184-mediated signaling. CD184 is a coreceptor for HIV entry by promoting Env-mediated fusion of the virus.Additional information: Clone REA649 displays negligible binding to Fc receptors. | Ísland
The development of this CXCR4 antibody was featured by Fisher et al. in the article Reassessment of CXCR4 Chemokine Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-2 (1). CXCR4 is a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in CXCR4 have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome ...
Neuropathic pain occurs as a result of damage and/or inflammation in the nervous system and presents as severe chronic pain. Neuroinflammation mediated by chemokines may be associated with the pathogenesis of neuropathic pain. Kiguchi et al. investigated the roles of the C-X-C chemokine ligand type 2 [macrophage inflammatory protein 2 (MIP-2)] and C-X-C chemokine receptor type 2 (CXCR2) in nerve injury-induced neuropathic pain. Expression of MIP-2 and CXCR2 were up-regulated and localized on accumulated neutrophils and macrophages in the injured sciatic nerve (SCN) after partial sciatic nerve ligation (PSL). MIP-2-neutralizing antibody or the CXCR2 antagonist N-(2-bromophenyl)-N′-(2-hydroxy-4-nitrophenyl)urea (SB225002) prevented PSL-induced tactile allodynia and thermal hyperalgesia. Both anti-MIP-2 and SB225002 suppressed up-regulation of inflammatory cytokines and chemokines in the injured SCN. Acetylation of histone H3 (AcK9-H3) on the promoter region of MIP-2 and CXCR2 was increased in ...
The results of the present study extend previously published data indicating that the CXCR4 receptor importantly modulates the migratory and angiogenic capacities of cultured human EPC. In line with recent studies indicating that progenitor cell trafficking is regulated by SDF-1,21-23 our data underscore the critical role of CXCR4 for homing of transplanted human EPC into ischemic tissues.. CXCR4 blockade not only resulted in impaired migratory activity toward SDF-1 as well as VEGF but was also associated with an impaired incorporation of EPC into sites of ischemia-induced neovascularization and disturbed restoration of blood flow to ischemic limbs, suggesting that CXCR4 is important for therapeutic integration of EPC into the vascular bed. The role of CXCR4 was supported by experiments using BM-MNC or EPC derived from spleen from heterozygous CXCR4+/− mice. CXCR4+/− cells showed an impaired capacity to induce recovery of ischemic blood flow after transplantation into ischemic nude mice. ...
POL6326 is an orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell-mobilization activities. CXCR4 inhibitor POL6326 binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation. This may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into blood. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types.
Atypical chemokine receptor 3 also known as C-X-C chemokine receptor type 7 (CXCR-7) and G-protein coupled receptor 159 (GPR159) is a protein that in humans is encoded by the ACKR3 gene.[1][2] This gene encodes a member of the G protein-coupled receptor family. This protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP) and was considered to be an orphan receptor. It is now classified as a chemokine receptor able to bind the chemokines CXCL12/SDF-1 and CXCL11. The protein is also a coreceptor for human immunodeficiency viruses (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. Whereas some reports claim that the receptor induces signaling following ligand binding, recent findings in zebrafish suggest that CXCR7 functions primarily by sequestering the chemokine CXCL12.[2] However, another recent study has provided ...
The ELR+ CXC chemokines play an important role in tumor growth and progression in a number of tumor model systems. IL-8/CXCL8 was the first described angiogenic, mitogenic, and motogenic chemokine in various cancer models and is the prototype of ELR+ CXC chemokines [8, 10-13]. This chemokine was initially discovered on the basis of its ability to induce mobilization of neutrophils and lymphocytes in vivo [9]. Like the basic fibroblast growth factor (bFGF) and the vascular endothelial growth factor (VEGF), it is a strong angiogenesis inducer. IL-8 mediates endothelial cell chemotaxis and proliferation in vitro and in vivo [36].. The fact that all ELR+CXC chemokines mediate angiogenesis highlights the importance of identifying a common receptor that mediates their biological functions in promoting angiogenesis. The candidate CXC chemokine receptors are CXCR1 and CXCR2. Only CXCL-8/IL-8 and CXCL-6 specifically bind to CXCR1 whereas all ELR+CXC chemokines bind to CXCR2. There is evidence that CXCR2 ...
Human cytomegalovirus (HCMV) is a widespread pathogen and a member of the Herpesviridae family. HCMV has a large genome that encodes many genes that are non-essential for virus replication but instead play roles in manipulation of the host immune environment. One of these is the US27 gene, which encodes a protein with homology to the chemokine receptor family of G protein-coupled receptors (GPCRs). The US27 protein has no known chemokine ligands but can modulate the signaling activity of host receptor CXCR4. We investigated the mechanism for enhanced CXCR4 signaling in the presence of US27 using a novel biosensor system comprised of fluorogen activating proteins (FAPs). FAP-tagged CXCR4 and US27 were used to explore receptor internalization and recovery dynamics, and the results demonstrate that significantly more CXCR4 internalization was observed in the presence of US27 compared to CXCR4 alone upon stimulation with CXCL12. While ligand-induced endocytosis rates were higher, steady state ...
Background: Metastasis, the spread and growth of tumor cells to distant organ sites, represents the most devastating attribute and plays a major role in the morbidity and mortality of cancer. Inflammation is crucial for malignant tumor transformation and survival. Thus, blocking inflammation is expected to serve as an effective cancer treatment. Among anti-inflammation therapies, chemokine modulation is now beginning to emerge from the pipeline. CXC chemokine receptor-4 (CXCR4) and its ligand stromal cell-derived factor-1 (CXCL12) interaction and the resulting cell signaling cascade have emerged as highly relevant targets since they play pleiotropic roles in metastatic progression. The unique function of CXCR4 is to promote the homing of tumor cells to their microenvironment at the distant organ sites. Methodology/Principal Findings: We describe the actions of N,N-(1,4-phenylenebis(methylene))dipyrimidin-2-amine (designated MSX-122), a novel small molecule and partial CXCR4 antagonist with ...
It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the
Methods Public DNA microarray data of synovial tissue from ADA treated RA patients was analyzed for changes in the expression level of various chemokines and their cognate receptors. PBMC populations from ADA treated RA patients taken at baseline, wks. 4 & 12 were assessed by CyTOF for CXCR4. IHC staining was performed on formalin paw sections from wk. 13 placebo control and ADA treated (1 mg/kg i.p.) huTNF Tg197 mice to evaluate CXCR4 expression in various pannus-associated cells. To assess the role of TNF and concomitant ADA treatment on human cultures in vitro, CXCR4 RNA expression was evaluated in RA-FLS treated with conditioned media from PBMCs +/-ADA for 6 hrs., and CXCR4 protein on OCP by flow cytometry in response to 72 hr. M-CSF+RANKL+/-TNF+/-ADA. To demonstrate the role of CXCR4 in OCgenesis, OCP were cultured for 6 d. in M-CSF+RANKL+/-TNF following 30 min. pretreatment with CXCR4 neutralizing antibody. OC maturation and activity were assessed by measuring TRAcP 5b activity and CTX-I ...
Repeated dosing of drugs targeting G protein-coupled receptors can stimulate antagonist tolerance, which reduces their efficacy; thus, strategies to avoid tolerance are needed. The efficacy of AMD3100, a competitive antagonist of the chemokine receptor CXCR4 that mobilizes leukemic blasts from the bone marrow into the blood to sensitize them to chemotherapy, is reduced after prolonged treatment. Tolerance to AMD3100 increases the abundance of CXCR4 on the surface of leukemic blasts, which promotes their rehoming to the bone marrow. AMD3100 inhibits both G protein signaling by CXCR4 and β-arrestin1/2-dependent receptor endocytosis. We demonstrated that biased antagonists of G protein-dependent chemotaxis but not β-arrestin1/2 recruitment and subsequent receptor endocytosis avoided tolerance. The peptide antagonist X4-2-6, which is derived from transmembrane helix 2 and extracellular loop 1 of CXCR4, limited chemotaxis and signaling but did not promote CXCR4 accumulation on the cell surface or ...
CXCR4 is a member of the chemokine receptor subfamily of seven transmembrane domained, G-protein coupled receptors, whose sole known natural ligand is CXCL12/SDF-1. CXCR4 is an unusual chemokine receptor by virtue of having expanded roles beyond leukocyte recruitment, including fundamental processes such as the development of the hematopoietic, cardiovascular, and nervous systems during embryogenesis. The receptor was first discovered as one of the co-receptors for HIV, and thereafter was also found to be expressed by multiple cancers including breast, prostate, lung, colon and multiple myeloma. A number of recent studies have correlated high levels of CXCR4 expression in cancers with poor prognosis and with resistance to chemotherapy, in part through enhancing interactions between cancers and stroma. A possible role for CXCR4, and chemokine receptors generally, in cancer and metastasis was first suggested in studies of breast cancer, showing that the receptor plays a role in directing metastatic cells
Regulation of cell migration by changes in oxygen availability is a central event during the organization of host response in inflammatory and neoplastic diseases as it may influence leukocyte recruitment and activation, angiogenesis, and metastasis formation (16). Here, we report that Hyp mediates selective up-regulation of CXCR4 in different cell types, including mononuclear phagocytes (monocytes, MDMs, and TAMs), endothelial cells, and cancer cells, and demonstrate that oxygen levels act as an important regulator of CXCR4 receptor expression. Our data also indicate that HIF-1 activation is involved in the Hyp-dependent up-regulation of CXCR4 expression and that the Hyp-HIF-1-CXCR4 circuit may participate in pathophysiological mechanisms under several conditions, ranging from inflammation to tumor angiogenesis and metastasis.. In contrast to standard cell culture conditions, characterized by 20% oxygen concentration, cells in the human body are exposed to much lower oxygen concentrations, ...
Primordial germ cells (PGCs) in the zebrafish embryo face a long migration from the point at which they are specified during development to the location of the future gonad, and it takes some precise signaling to get them there. Major guidance cues are provided by the chemokine SDF-1a (stromal-derived factor-1 alpha), which attracts the PGCs by signaling through its receptor CXCR4b [chemokine (C-X-C motif) receptor 4b]. SDF-1a also binds to another receptor, CXCR7, but the function of this receptor in PGC cell migration has been uncertain. Boldajipour et al.s experiments indicate that CXCR7s function is not to signal but rather to act as a sink that soaks up stray molecules of SDF-1a, thus adding to the precision of SDF-1a signaling through CXCR4b. Transplantation experiments taking PGCs from animals lacking CXCR7 into wild-type embryos showed that the critical function of CXCR7 was in somatic cells, not the PGCs. Microscopy of fluorescently tagged proteins showed that CXCR7 promoted ...
Although overexpression of DARPP-32 has been identified in several malignancies such as gastric, esophageal, colon, and breast cancers (4, 23, 24), the full spectrum of its biologic functions in cancer remains uncharacterized. The ability of cancer cells to invade the nearby tissues and blood vessels is one of the crucial steps that determine the metastatic potential of a tumor (8, 9, 25, 26). In this study, we show a novel molecular mechanism by which DARPP-32 regulates CXCR4 and mediates cancer cell invasion.. The human chemokine superfamily includes at least 46 ligands, which bind to 18 functionally signaling G-protein-coupled receptors and 2 decoy or scavenger receptors (27). The chemokine CXCL-12/SDF-1 binds to the receptors CXCR4 and CXCR7 (28, 29). The chemokine receptor CXCR4 and its ligand CXCL-12/SDF-1 are known to play an important role in the development of invasion and metastases in several malignancies including gastric cancer (30, 31). The current study examined a hypothesis that ...
Naïve T cells, when activated by specific antigen and cytokines, up-regulate adhesion molecules as well as chemokine receptors on their surface, which allows them to migrate to inflamed tissues. Human studies have shown that CXCR3 is one of the chemokine receptors that is induced during T cell activation. Moreover, CXCR3-positive T cells are enriched at inflammatory sites in patients with autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. In this study, we use a mouse model of inflammation to demonstrate that CXCR3 is required for activated T cell transmigration to inflamed tissue. Using an anti- mCXCR3 antibody, we have shown that in vitro-differentiated T helper (Th) 1 and Th2 cells up-regulated CXCR3 upon stimulation with specific antigen/major histocompatibility complex. However, only Th1 cells, when adoptively transferred to syngeneic recipients, are efficiently recruited to the peritoneum in an adjuvant-induced peritonitis model. Furthermore, the neutralizing anti-mCXCR3
Purified Recombinant Human CXCR2 HEK293T cell lysate from Creative Biomart. Recombinant Human CXCR2 HEK293T cell lysate can be used for research.
Chow et al. demonstrated that CXCR3 expression on intratumoral CD8+ T cells, and the expression of its ligand, CXCL9, by intratumoral CD103+ DCs was required for the efficacy of PD-1 blockade. Anti-PD-1 expanded CXCR3+CD8+ T cells within MC38 tumors in mice and increased CXCL9 and CXCL10 production by DCs, leading to an enhanced antitumor response, likely via more frequent DC-T cell interactions. Across solid murine tumors, baseline intratumoral expression of CXCR3 ligands correlated with response to PD-1 blockade. In melanoma patients treated with anti-PD-1, early post-treatment levels of CXCR3 ligands correlated with response.
Synonyms for CXCR4 in Free Thesaurus. Antonyms for CXCR4. 34 synonyms for whim: impulse, sudden notion, caprice, fancy, sport, urge, notion, humour, freak, craze, fad, quirk, conceit, vagary, whimsy, passing thought. What are synonyms for CXCR4?
Chemoattractant (PubMed:11859124). Activates the C-X-C chemokine receptor cxcr4 to induce a rapid and transient rise in the level of intracellular calcium ions, and chemotaxis (PubMed:11859124). Signaling with cxcr4 mediates the directional movement of mesodermal cells during gastrulation (Ref.2). Binds to the allosteric site (site 2) of integrins and activates them in a cxcr4-independent manner. [-] ...
CXCR3 antibody [CXCR3-173] (chemokine (C-X-C motif) receptor 3) for FACS, Neut. Anti-CXCR3 mAb (GTX14657) is tested in Mouse samples. 100% Ab-Assurance.
Purpose: To identify the miRNA regulators of C-X-C motif chemokine receptor 4 (CXCR4) and the underlying mechanism as well as the therapeutic and prognostic values in human glioblastoma (GBM).. Experimental Design: miRNA profile analyses and bioinformatics predictions were used to identify the mediators of CXCR4, which were confirmed by luciferase reporter assay, Western blot assay and immunohistochemistry. The effects of miR-663 on CXCR4-mediated GBM malignancy were investigated by gain-of-function experiments. Orthotopic xenografts derived from constitutive or induced miR-663-expressing GBM cells were used to determine the antitumor effects of miR-663 and CXCR4-specific antagonist AMD3100. Bivariate correlation analyses were used to examine the correlation of miR-663 and CXCR4 levels in glioma. The prognostic values of miR-663 and CXCR4 were examined in 281 cases of astrocytic glioma from our hospital and 476 cases of GBM from The Cancer Genome Atlas database using the multivariate Cox ...
Les chimiokines sont des petites protéines secrétées dont la fonction principale est la stimulation de la migration de cellules immunitaires vers différents organes et tissus. Elles sont souvent impliquées lors des maladies inflammatoires, auto-immunes et des cancers. Ainsi, les chimiokines et leurs récepteurs couplés aux protéines G (RCPG) sont la cible pharmacologique de plusieurs molécules, actuellement testées en essais cliniques. Nous avons pris comme modèle, lors de notre étude, le récepteur atypique CXCR7. Ce récepteur est dit atypique, car il ne signalise pas via la voie classique des protéines G, mais plutôt via la voie de la β-arrestine. CXCR7 est impliqué dans de nombreux cancers, favorise la progression métastatique et est un co-récepteur pour le virus de limmunodéficience humaine (VIH). Cependant, aucune donnée sur son mode de liaison avec ses ligands CXCL11/ITAC et CXCL12/SDF-1 nexiste à date. Nous pensons que cette information est essentielle pour le ...
HEK293T-HuCXCR4-FLAG cell line is a hypotriploid human cell line, which has been transfected with a Human chemokine (C-X-C motif) receptor 4 (CXCR4) tagged in the N-terminus with FLAG to allow stably express of the human CXCR4 tagged in the N-terminus with FLAG protein. It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplification system.
p210BCR-ABL inhibits SDF-1 chemotactic response via alteration of CXCR4 signaling and down-regulation of CXCR4 expression. Cancer Res. 2005 Apr 01; 65(7):2676-83 ...
In this study, we show that the chemokine SDF-1 and its cognate receptor CXCR4 are expressed in breast cancer in vivo and analyze the effects of manipulating these proteins in a coculture model of mammary carcinoma and vascular endothelial cells. The evidence presented suggests that activation of the SDF-1/CXCR4 axis in a growing tumor contributes to angiogenesis and the initial steps of metastasis. CXCR4 activation had surprisingly similar effects on tumor and endothelial cells: it induced proliferation and migration. In addition, SDF-1 binding to CXCR4 led to specific effects on endothelial and tumor cells: in endothelial cells, CXCR4 stimulated tube formation which may point to proangiogenic activity in vivo, whereas in the tumor cells activation of this receptor resulted in adhesion to endothelial cells and transendothelial migration.. In addition to their hematopoietic activities, SDF-1 and CXCR4 have been implicated in the regulation of angiogenesis in a number of (patho)physiological ...
Complete information for CXCR5 gene (Protein Coding), C-X-C Motif Chemokine Receptor 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
趋化因子受体-4 (chemokine receptor-4,CXCR4)属趋化因子家族,为G蛋白偶联的7次跨膜受体蛋白,基质细胞衍生因子-12是该受体的唯一配体。目前发现CXCR4在23种不同类型肿瘤中均有表达,与肿瘤细胞的增殖、侵袭、转移及预后密切相关,针对CXCR4靶向治疗可望成为肿瘤基因治疗研究的新热点。
Although there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. Initial interest in pursuing the CXCR4-CXCL12 axis as a target for cancer therapy was fueled by observations implicating CXCR4 in promoting metastasis (2, 28). CXCR4 is expressed in at least 20 different human cancers (8, 29-33); CXCR7 is also expressed in tumors and found to be involved in cell growth, survival, and metastasis (34, 35). Like CXCR4, it is expressed on tumor-associated vessels and on neovasculature (36). On the other hand, CXCL12 is secreted in the tumor microenvironment by stromal cells (21, 28). On the basis of the data such as these, it has been thought that CXCR4 antagonism could prevent the development of metastases by targeting multiple steps in the process of dissemination. Restricted by the tumor type, inhibiting CXCR4 should interfere with tumor cell growth, migration and chemotaxis, and homing toward secondary ...
Abnormal CXCR4 surface expression in solid tumors, has been shown to be responsible for their metastasis to particular organs with high CXCL12 levels (e.g., lymph nodes, bones, and bone marrow (BM)), and have prognostic significance for disease progression in breast, colorectal, and renal cancers, and hepatocellular carcinoma. In leukemia, CXCR4 expression conferred leukemic blasts with a higher capacity to seed into BM niches, thereby protecting leukemic cells from chemotherapy-induced apoptosis, and was correlated with shorter disease-free survival. Conversely, neutralizing the interactions of CXCL12/CXCR4 disrupted metastasis, induced apoptosis, and increased chemosensitivity in solid cancers and leukemia.
Patterns of CXCL12, CXCR7, and CXCR4 mRNAs in the early developing kidney.Adjacent kidney sections were hybridized with radiolabeled antisense riboprobes for CX
CD185 (CXCR5), FITC, clone: MU5UBEE, eBioscience™ 25 Tests; FITC CD185 (CXCR5), FITC, clone: MU5UBEE, eBioscience™ Primary Antibodies CD151 to CD200
CD185 (CXCR5), PerCP-eFluor™ 710, clone: MU5UBEE, eBioscience™ 100 Tests; PerCP-eFluor™ 710 CD185 (CXCR5), PerCP-eFluor™ 710, clone: MU5UBEE,...
CXCR3 Agonist, PS372424 - Calbiochem The CXCR3 Agonist, PS372424 controls the biological activity of CXCR3. This small molecule/inhibitor is primarily used for Cell Signaling applications. - Find MSDS or SDS, a COA, data sheets and more information.
141117DNAHomo sapiensmisc_featurePolynucleotide coding for N-ter domain of CXCR4 1atggagggga tcagtatata cacttcagat aactacaccg aggaaatggg ctcaggggac 60tatgactcca tgaaggaacc ctgtttccgt gaagaaaatg ctaatttcaa taaaatc 117239PRTHomo sapiensmisc_featureN-ter domain of CXCR4 2Met Glu Gly Ile Ser Ile Tyr Thr Ser Asp Asn Tyr Thr Glu Glu Met1 5 10 15Gly Ser Gly Asp Tyr Asp Ser Met Lys Glu Pro Cys Phe Arg Glu Glu20 25 30Asn Ala Asn Phe Asn Lys Ile353822DNAArtificial sequenceA chimeric fusion comprised of CXCR4 peptide coding sequence fused to an immunoglobulin cDNA 3atggagggga tcagtatata cacttcagat aactacaccg aggaaatggg ctcaggggac 60tatgactcca tgaaggaacc ctgtttccgt gaagaaaatg ctaatttcaa taaaatcctc 120gagcccaaat cttgtgacaa aactcacaca tgcccaccgt gcccagcacc tgaactcctg 180gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 240acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 300gactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 360tacaacagca cgtaccgtgt ggtcagcgtc ...
Activation of CXCR4 by the CXC chemokine stromal cell-derived factor-1 (SDF-1) requires interaction of the amino-terminal domains of both molecules. We report that proteinases released from either mononucleated blood cells or polymorphonuclear neutrophils degranulated by inflammatory stimuli generate an SDF-1 fragment that is deleted from amino-terminal residues Lys(1)-Pro(2)-Val(3), as characterized by mass spectrometry analysis. The proteolyzed chemokine fails to induce agonistic functions and is unable to prevent the fusogenic capacity of CXCR4-tropic human immunodeficiency viruses. Furthermore, we observed that exposure of CXCR4-expressing cells to leukocyte proteinases results in the proteolysis of the extracellular amino-terminal domain of the receptor, as assessed by flow cytometry analysis and electrophoretic separation of immunoprecipitated CXCR4. Blockade of SDF-1 and CXCR4 proteolysis by the specific leukocyte elastase inhibitor, N-methoxysuccinyl-alanine-alanine-proline-valine-chloromethyl
TY - JOUR. T1 - The role of metabotropic glutamate receptor 5 on the stromal cell-derived factor-1/CXCR4 system in oral. AU - Kuribayashi, Nobuyuki. AU - Uchida, Daisuke. AU - Kinouchi, Makoto. AU - Takamaru, Natsumi. AU - Tamatani, Tetsuya. AU - Nagai, Hirokazu. AU - Miyamoto, Youji. PY - 2013/11/13. Y1 - 2013/11/13. N2 - We have demonstrated that blocking CXCR4 may be a potent anti-metastatic therapy for CXCR4-related oral cancer. However, as CXCR4 antagonists are currently in clinical use to induce the mobilization of hematopoietic stem cells, continuous administration as an inhibitor for the metastasis may lead to persistent leukocytosis. In this study, we investigated the novel therapeutic downstream target(s) of the SDF-1/CXCR4 system, using B88-SDF-1 cells, which have an autocrine SDF-1/CXCR4 system and exhibit distant metastatic potential in vivo. Microarray analysis revealed that 418 genes were upregulated in B88-SDF-1 cells. We identified a gene that is highly upregulated in B88-SDF-1 ...
The mild neuroinflammation hypothesis of schizophrenia was introduced by Bechter in 2001.It has been hypothesized that a hypofunction of glutamatergic signaling via N-methyl-n-aspartate receptors (NMDARs) and hyperactivation of dopamine D2 receptors play a role in schizophrenia. The triplet puzzle theory states that sets of triplet amino acid homologies guide two different receptors towards each other and contributes to the formation of a receptor heteromer. It is therefore proposed that putative NMDAR- C-C chemokine receptor type 2 (CCR2), NMDAR- C-X-C chemokine receptor type 4 (CXCR4) and NMDAR- Interleukin 1 receptor type II (IL1R2) heteromers can be formed in the neuronal networks in mild neuroinflammation due to demonstration of Gly-Leu-Leu (GLL), Val-Ser-Thr (VST) and/or Ser-Val-Ser (SVS) amino acid homologies between these receptor protomers. This molecular process may underlie the ability to produce symptoms of schizophrenia in mild neuroinflammation. In this state volume transmission is
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently seven known CXC chemokine receptors in mammals, named CXCR1 through CXCR7. CXCR1 and CXCR2 are closely related receptors that recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (otherwise known as interleukin-8) and CXCL6 can both bind CXCR1 in humans, while all other ELR-positive chemokines, such as CXCL1 to CXCL7 bind only CXCR2. They are both expressed on the surface of neutrophils in mammals. CXCR3 is expressed predominantly on T cells (T lymphocytes), and also on other lymphocytes [some B cells (B lymphocytes) and NK cells] and is highly induced following cell activation. There are two ...
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function mutations in chemokine receptor CXCR4. Patient WHIM-09 was spontaneously cured by chromothriptic deletion of 1 copy of 164 genes, including the CXCR4WHIM allele, presumably in a single hematopoietic stem cell (HSC) that repopulated HSCs and the myeloid lineage. Testing the specific contribution of CXCR4 hemizygosity to her cure, we previously demonstrated enhanced engraftment of Cxcr4+/o HSCs after transplantation in WHIM (Cxcr4+/w) model mice, but the potency was not quantitated. We now report graded-dose competitive transplantation experiments using lethally irradiated Cxcr4+/+ recipients in which mixed BM cells containing approximately 5 Cxcr4+/o HSCs and a 100-fold excess of Cxcr4+/w HSCs achieved durable 50% Cxcr4+/o myeloid and B cell chimerism in blood and approximately 20% Cxcr4+/o HSC chimerism in BM. In Cxcr4+/o/Cxcr4+/w parabiotic mice, we ...
Among chemokine receptors, CXCR4 has been found to be most widely expressed in multiple types of tumors and has been shown to be implicated in tumor cell invasion, metastasis, as well as in survival and proliferation (2, 5). Less information is available on the occurrence and biological role of the newly discovered second receptor for the CXCR4-ligand CXCL12, i.e., CXCR7 (8, 12-14). Reportedly, human gliomas and astrocytomas produce several chemokines like CCL2/MCP-1, CXCL8/interleukin-8, CXCL10, CXCL11/I-TAC, CXCL12/stromal cell-derived factor-1, and CXCL16 (19, 26). Their corresponding receptors have been identified either on astrocytoma/glioma cells (or subsets), on tumor-infiltrating microglial cells/macrophages, on tumor endothelial cells, or on tumor-infiltrating neural stem cells (17, 27).. CXCR4 has been originally described as a major widespread receptor on glioma cells (3, 4), and its occurrence and localization were addressed in several previous studies. WHO grade 3 and 4 glial tumors ...
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function mutations in chemokine receptor CXCR4. Patient WHIM-09 was spontaneously cured by chromothriptic deletion of 1 copy of 164 genes, including the CXCR4WHIM allele, presumably in a single hematopoietic stem cell (HSC) that repopulated HSCs and the myeloid lineage. Testing the specific contribution of CXCR4 hemizygosity to her cure, we previously demonstrated enhanced engraftment of Cxcr4+/o HSCs after transplantation in WHIM (Cxcr4+/w) model mice, but the potency was not quantitated. We now report graded-dose competitive transplantation experiments using lethally irradiated Cxcr4+/+ recipients in which mixed BM cells containing approximately 5 Cxcr4+/o HSCs and a 100-fold excess of Cxcr4+/w HSCs achieved durable 50% Cxcr4+/o myeloid and B cell chimerism in blood and approximately 20% Cxcr4+/o HSC chimerism in BM. In Cxcr4+/o/Cxcr4+/w parabiotic mice, we ...
Oregon Grape, a popular source of Berberine. SDF-1 binds to a receptor named CXCR-4 (short for C-X-C chemokine receptor type 4. SDF-1 is sometimes referred to as CXCL12, thats where the CXC comes from, but lets try to keep this simple).. Leukemia tumor cells express this CXCR-4 receptor either on their surface or inside the cell. They notice and respond to SDF-1. This cSFD-1/CXCR4 signaling pathway involved in the migration of leukemic cells though the body. A 2008 paper by Li et al reported that because berberine … could partly inhibit SDF-1 induced AML [acute myeloid leukemia] cells as well as LSCs [leukemic stem cells] migration…… [the authors] hypothesized that berberine could inhibit AML cells migration partly by reducing the secreting of SDF-1 …... Therefore, [they] speculated that berberine might be a potentially effective agent for prevention of leukemia. [1] This hypothesis was based in part by an earlier paper by Tavor et al that looked at the role of CXCR4 in the ...
Particular populations of stem cells in the bone marrow harbors the membrane receptor CXCR4 which is a specific receptor for chemokine stromal cell-derived factor (SDF-1). In addition, the presence of CXCR4 identifies cells showing expression of early cardiac, muscle and endothelial markers. In mice experiments it was shown that bone marrow contains pools of cells that express early cardiac lineage markers (Nkx2.5/Csx, GATA-4, and MEF2C) and the population can be mobilised by inducing the myocardial infarction. This is the first proof that postnatal bone marrow contains nonhematopoietic population of cells that express markers for cardiac differentiation [4-6]. The peak expression of cardiac markers was found at the same time as most significant increase of stem cells number was measured [12]. A Similar phenomenon seems to occur in humans in the setting of AMI [10]. The SDF-1/CXCR-4 axis seems particularly important in stem/progenitor cell homing, chemotaxis, engrafment and retention in ...
IPF is a progressive disease for which two antifibrotic drugs have recently been approved, however there is an unmet need to predict responses to antifibrotic treatment, such as pirfenidone. Recent data suggested that up-regulated expression of the C-X-C chemokine-receptor type 4 (CXCR4) is indicative of outcomes in IPF.Can quantitative, molecular imaging of pulmonary CXCR4 expression as a biomarker for disease activity predict response to the targeted treatment pirfenidone and prognosis in patients with IPF?CXCR4 expression was analyzed by immunohistochemistry of lung tissues and RT-PCR of BAL. PET-CT with the specific CXCR4 ligand, gallium-68 (68Ga)-pentixafor, was performed in 28 IPF patients (PET1) and compared with baseline clinical characteristics. In 16 patients, a follow-up scan (PET2) was obtained 6-12 weeks after initiation of treatment with pirfenidone. Patients were followed in our outpatient clinic for ≥12 months.Immunohistochemistry showed high CXCR4 staining of epithelial cells ...
The version of the article, Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4 by Wu et al that published online ahead-of-print on February 28, 2013, and appears in the May issue (Stroke. 2013;44:1402-1409) contained an error in Ying-Chao Changs affiliation. The correct affiliation is Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. The authors regret the error.. This correction has been made to the online version of the article, which is available at http://stroke.ahajournals.org/content/44/5/1402.. ...
Looking for online definition of CXCR1 in the Medical Dictionary? CXCR1 explanation free. What is CXCR1? Meaning of CXCR1 medical term. What does CXCR1 mean?
The role of SDF-1/CXCR4 in the vasculogenesis and remodeling of cerebral arteriovenous malformation Lingyan Wang,1 Shaolei Guo,2 Nu Zhang,2 Yuqian Tao,3 Heng Zhang,1 Tiewei Qi,2 Feng Liang,2 Zhengsong Huang2 1Department of Neurosurgery ICU, 2Department of Neurosurgery, 3Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China Background: Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM.Methods: Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, VEGF-A, and HIF-1 by using immunohistochemical staining. Flow cytometry was used to quantify the level of circulating endothelial
Hypoxia, a hallmark of malignant tumors, often correlates with increasing tumor aggressiveness and poor treatment outcomes. Due to a lack of vasculature, effective drug delivery to hypoxic tumor regions remains challenging. Signaling through the chemokine SDF-1alpha and its receptor CXCR4 plays a critical role in the homing of stem cells to ischemia for potential use as drug-delivery vehicles. To harness this mechanism for targeting tumor hypoxia, we developed polymeric nanoparticle-induced CXCR4-overexpressing human adipose-derived stem cells (hADSCs). Using glioblastoma multiforme (GBM) as a model tumor, we evaluated the ability of CXCR4-overexpressing hADSCs to target tumor hypoxia in vitro using a 2D migration assay and a 3D collagen hydrogel model. Compared to untransfected hADSCs, CXCR4-overexpressing hADSCs showed enhanced migration in response to hypoxia and penetrated the hypoxic core within tumor spheres. When injected in the contralateral brain in a mouse intracranial GBM xenograft, ...
Everolimus (RAD001, Afinitor) is an mTOR inhibitor FDA-approved for the treatment of patients with advanced clear cell renal cancer (RCC) after failure of treatment with sunitinib or sorafenib, or both drugs. It targets the mammalian target of rapamycin (mTOR) complex inhibiting a serine/threonine kinase regulating PI3K/AKT signaling pathway. Previous evidences demonstrated that the activation of the chemokine receptor CXCR4 involved the mTOR pathway and that CXCR4 was overexpressed in RCC. Recently, also the deorphanized chemokine receptor CXCR7 was described in RCC and defined as an independent prognostic factor. Nevertheless, little is known about the CXCR4-CXCL12-CXCR7-induced signalling. Aim of the study was to investigate if the CXCL12/CXCR4/CXCR7 complex could transduce the signal through mTOR identifying new therapeutic targets. In human renal cancer cells (RXF393, A498) treatment with CXCL12, the CXCR4 and CXCR7 ligand, induced mTOR pathway, as demonstrated through p70S6K and eukaryotic ...
The CXCR3 receptor and its three interferon-inducible ligands (CXCL9, CXCL10 and CXCL11) have been implicated as playing a central role in directing a Th1 inflammatory response. Recent studies strongly support that the CXCR3 receptor is a very attractive therapeutic target for treating autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and psoriasis, and to prevent transplant rejection. We describe here the in vitro and in vivo pharmacological characterizations of a novel and potent small molecule CXCR3 antagonist, SCH 546738. In this study, we evaluated in vitro pharmacological properties of SCH 546738 by radioligand receptor binding and human activated T cell chemotaxis assays. In vivo efficacy of SCH 546738 was determined by mouse collagen-induced arthritis, rat and mouse experimental autoimmune encephalomyelitis, and rat cardiac transplantation models. We show that SCH 546738 binds to human CXCR3 with a high affinity of 0.4 nM. In addition, SCH 546738 displaces radiolabeled CXCL10
CXCL12 [ENSP00000379140]. Pre-B cell growth-stimulating factor; Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. SDF-1-beta(3-72) and SDF-1- alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3- 67) and thus to preserve activity on local sites. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of ...
In general terms, the systemic inflammatory response is an entirely normal host response to remove pathogens; however, if excessive, it may lead to damage to host tissues of lung and liver systems, multiple organ dysfunction syndrome, and a high mortality rate (3). Because it is well established that chemokines play a key role in controlling leukocyte recruitment and activation, many researchers have investigated the role of chemokine receptors during sepsis (17). Most of these studies have focused on CXC chemokine receptors, especially CXCR1 and CXCR2. Mice deficient in CXCR2 or treated with CXCR2-specific antibodies are protected from developing sepsis (14). Blockade of CXCR2 by antileukinate, a hexapeptide inhibitor of CXC-chemokine receptor, significantly attenuates lung damage (9). Moreover, pepducins derived from intracellular loops of CXCR1 and CXCR2 reverse the lethal consequence of sepsis, including disseminated intravascular coagulation and multiple organ failure in mice (8).. Recent ...
Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR+ luminal tumor cells and AR− neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR+ luminal cells. We demonstrate that the combination of CXCR2 inhibition and AR targeting is an effective treatment strategy in mouse xenograft models. Such a strategy has the potential to overcome therapy resistance caused by tumor cell heterogeneity. ...
Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for ...
Purpose: : Stromal cell-derived factor-1 (SDF-1) was reported to have significant functions in retinal angiogenesis and the recruitment of hematopoietic stem cell-derived cells. We here assessed the contribution of the SDF-1/CXCR4 axis to the neovascular sprouting from the retinal vasculature in ex vivo and in vivo models. Methods: : (ex vivo) The retinas isolated from 7- to 8-week-old C57BL6/J mice were cultured for 4 days with 25 ng/ml vascular endothelial growth factor (VEGF), with or without anti-SDF-1 antibody or CXCR4 inhibitor (AMD 3100). The neovascular sprouts (PECAM-positive and collagen type IV negative sprouts) were quantified. For the time-sequential imaging, the retinas of Tie2-GFP transgenic mice were treated with VEGF for 4 days, followed by AMD 3100 treatment and the image acquisition. (in vivo) AMD3100 was intraperitoneally injected into C57BL6/J mice on postnatal day 3 (P3), and the eyes were isolated and fixed on P4. After the staining with anti-PECAM antibodies, the radius ...
Chemokine receptors play a role in leukocyte recruitment, activation, and maintaining effector functions and regulate adaptive immune response and angiogenesis. The study aimed at flow cytometric analysis of T cell subsets with selected surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptor combination in peripheral blood of children with chronic kidney disease (CKD) on hemodialysis (HD). The percentage of T lymphocytes with CD8 and combined CD28,CCR7 expression was higher in HD children. The percentage of T lymphocytes expressing CCR7, CD28,CCR7, and CXCR4,CD8 was increased in children on conservative treatment. Total number (tn) of CXCR4+ cells was reduced in children on hemodialysis. The tn of T CXCR3+ cells was lower in children on conservative treatment. During HD the percentage of T CD4+ cells was higher and of T CXCR3+ lymphocytes was lower after HD session as compared to 15 min of session duration. During HD tn of T cells with expression of CCR4, CCR5, CCR7, CXCR3,
Since the original descriptions of the role of stromal cell-derived factor (SDF)-1 in recruiting bone marrow derived stem cells to the sites of vascular1 and myocardial injury,2 there has been increasing evidence of the broader importance of the SDF-1:CXCR4 axis in regulating myocardial repair following ischemic injury.2-6 In this issue of Circulation Research, Tang et al investigate the role of the SDF-1:CXCR4 axis in the recruitment of exogenously derived cardiac stem cells.7 They further investigate how cardiac stem cell exposure to hypoxia before their intravenous administration alters cardiac stem cell engraftment and subsequent effects on myocardial repair.. Cardiac stem cells were derived from cardiosphere cultures and were defined by as CLK (cardiosphere-derived c-Kit+ Lin−) cells. The cells were shown to have evidence of cardiac potential through the expression of green fluorescent protein under control of the Nkx2.5 promoter. The cells were administered intravenously 1 hour following ...
Novel Stromal Cell-Derived Factor-1 Polypeptides, Polynucleotides, Modulators Thereof and Methods of Use - diagram, schematic, and image 01 ...
Ubiquitination of the chemokine receptor CXCR4 serves as a targeting signal for lysosomal degradation, but the mechanisms mediating ubiquitination and lysosomal sorting remain poorly understood. Here we report that the Nedd4-like E3 ubiquitin ligase AIP4 mediates ubiquitination of CXCR4 at the plasm …
TY - JOUR. T1 - Use of shRNA for stable suppression of chemokine receptor expression and function in human cancer cell lines. AU - Salazar, Nicole. AU - Muñoz, Daniel. AU - Hoy, James. AU - Lokeshwar, Bal L.. PY - 2014. Y1 - 2014. N2 - In this chapter, we describe a protocol used for stable silencing of chemokine receptor CXCR7 in human cancer cells using shRNA in a lipid transfection setting, previously published by our laboratory. We provide thorough detail and background information about the process of shRNA to clarify the importance of this process. We use CXCR7 shRNA and scrambled sequence shRNA constructs cloned into a pRS plasmid under the control of a U6 promoter for stable expression. Human cancer cells are transfected with shRNA-pRS using Lipofectamine 2000. Cells stably expressing the shRNA are selected from transfected cultures following 2 weeks in medium containing the selection antibiotic puromycin. The emergent cell colonies are evaluated for knockdown of CXCR7 mRNA and protein ...
Previous studies have demonstrated that the process of tumor metastasis is closely associated with EMT (24,25). The crucial feature of the EMT process is that epithelial cells lose cell-cell adhesion molecules, including E-cadherin (32,33), and express mesenchymal proteins, such as N-cadherin, to acquire motility (34), which could enhance the invasion of tumor cells into adjacent tissues and promote metastasis to distant sites (35). Numerous studies have also demonstrated that various signaling pathways are involved in the regulation of EMT in tumor cells or in the microenvironment (21,36-38). It has been well documented that the CXCL12/CXCR4 axis promotes EMT and metastasis in numerous different types of cancer cells. For example, the CXCL12/CXCR4 axis increases microRNA-125b expression and induces EMT in human colorectal cancer (21). Additionally, the overexpression of CXCL12 and CXCR4 in esophageal cancer stem cells accelerates esophageal tumor spread and metastasis (39). Conversely, blocking ...
Novel bio-reducible polymer compositions which combine the ability to act as a CXCR4 antagonist and simultaneously provide enhanced gene delivery through the formation of inert nanocarrier polyplexes have been developed. As would be expected for biodegradable polymers, the cytotoxicity of these nanocarrier compositions are very low with measured IC50 values 50 to 100 times higher than conventional polyethylenimines (PEI) controls. Significantly, the known CXCR4 antagonist drug AMD3100 has successfully been incorporated into the polymer composition and shown to retain activity comparable or better than the drug alone with or without the formation of a nanocarrier polyplexes. Successful gene delivery by the nanocarrier polyplexes has been demonstrated through fluorescence imaging studies and measurements of transfected gene expression levels. Preliminary results of two different animal studies confirm the CXCR4 antagonist response of this novel composition for both lung cancer metastasis and ...
Mice. Male 6- to 12-week-old WT BALB/cJ (CD45.2+), BALB/cByJ (CD45.2+), and syngeneic CByJ.SJL(B6)-Ptprca/J (CD45.1+) as well as WT C57BL/6J and syngeneic B6.SJL-Ptprca Pep3b/BoyJ (CD45.1+), WT DBA/2J, and FVB/NJ mice were purchased from the Jackson Laboratory. The knockout strains C.129S2(B6)-Cxcr2tm1Mwm/J (CXCR2-KO, BALB/cJ background), B6.FVB(Cg)-Mmp9tm1Tvu/J (MMP9-KO, C57BL/6J background), FVB.Cg-Mmp9tm1Tvu/J (MMP9-KO, FVB/NJ background), B6.129S7-Itgaltm1Bll/J (CD11a-KO, C57BL/6J background), and B6.129S4-Itgamtm1Myd/J (CD11b-KO, C57BL/6J background) were also obtained from Jackson Laboratory. Endothelial-specific CXCR2 ablated mice were generated by crossing C57BL/6-Cxcr2tm1Rmra/J (CXCR2fl/fl, Jackson Laboratory) and B6;129-Tg(Cdh5-cre)1Spe/J (Cdh5Cre, Jackson Laboratory) mice. Mobilization experiments were performed with Cxcr2fl/flCre+ mice (CXCR2fl/WTCre+ were used as controls) reconstituted with WT BM from syngeneic B6.SJL-Ptprca Pep3b/BoyJ (CD45.1+, Jackson Laboratory) donors. ...
Mice. Male 6- to 12-week-old WT BALB/cJ (CD45.2+), BALB/cByJ (CD45.2+), and syngeneic CByJ.SJL(B6)-Ptprca/J (CD45.1+) as well as WT C57BL/6J and syngeneic B6.SJL-Ptprca Pep3b/BoyJ (CD45.1+), WT DBA/2J, and FVB/NJ mice were purchased from the Jackson Laboratory. The knockout strains C.129S2(B6)-Cxcr2tm1Mwm/J (CXCR2-KO, BALB/cJ background), B6.FVB(Cg)-Mmp9tm1Tvu/J (MMP9-KO, C57BL/6J background), FVB.Cg-Mmp9tm1Tvu/J (MMP9-KO, FVB/NJ background), B6.129S7-Itgaltm1Bll/J (CD11a-KO, C57BL/6J background), and B6.129S4-Itgamtm1Myd/J (CD11b-KO, C57BL/6J background) were also obtained from Jackson Laboratory. Endothelial-specific CXCR2 ablated mice were generated by crossing C57BL/6-Cxcr2tm1Rmra/J (CXCR2fl/fl, Jackson Laboratory) and B6;129-Tg(Cdh5-cre)1Spe/J (Cdh5Cre, Jackson Laboratory) mice. Mobilization experiments were performed with Cxcr2fl/flCre+ mice (CXCR2fl/WTCre+ were used as controls) reconstituted with WT BM from syngeneic B6.SJL-Ptprca Pep3b/BoyJ (CD45.1+, Jackson Laboratory) donors. ...
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Recent work identified the murine gene homologous to the human T cell attracting chemokine CXC receptor ligand 11 (CXCL11, also termed I-TAC, SCYB11, ss-R1, H174, IP-9). Here, the biological activity and expression patterns of murine CXCL11 relative to CXCL9 (MIG) and CXCL10 (IP-10/crg-2), the other …
1. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y. et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996;382:635-8 2. Tachibana K, Hirota S, Iizasa H, Yoshida H, Kawabata K, Kataoka Y. et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature. 1998;393:591-4 3. Pelus LM, Fukuda S. Chemokine-mobilized adult stem cells; defining a better hematopoietic graft. Leukemia. 2008;22:466-73 4. Lapidot T, Dar A, Kollet O. How do stem cells find their way home?. Blood. 2005;106:1901-10 5. Massberg S, Schaerli P, Knezevic-Maramica I, Kollnberger M, Tubo N, Moseman EA. et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell. 2007;131:994-1008 6. Hoggatt J, Pelus LM. Eicosanoid regulation of hematopoiesis and hematopoietic stem and progenitor trafficking. Leukemia. 2010;24:1993-2002 7. Ratajczak MZ, ...
Rabbit monoclonal antibody raised against synthetic protein of human CXCR3. A synthetic peptide corresponding to human CXCR3. (MAB22014) - Products - Abnova
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The antileukemic effect of inhibiting bromodomain and extra-terminal domain-containing (BET-containing) proteins (BETPs) such as BRD4 has largely been largely attributed to transcriptional downregulation of cellular anabolic and antiapoptotic processes, but its effect on the bone marrow microenvironment, a sanctuary favoring the persistence of leukemic stem/progenitor cells, is unexplored. Sustained degradation of BETP with the small-molecule BET proteolysis-targeting chimera (PROTAC) ARV-825 resulted in a marked downregulation of surface CXCR4 and CD44, key proteins in leukemia-microenvironment interactions, in acute myeloid leukemia (AML) cells. Abrogation of surface CXCR4 expression impaired SDF-1α-directed migration and was mediated through transcriptional downregulation of PIM1 kinase, which in turn phosphorylates CXCR4 and facilitates its surface localization. Downregulation of CD44, including isoforms CD44v8-10 impaired cystine uptake, lowered intracellular reduced glutathione, and ...
The antileukemic effect of inhibiting bromodomain and extra-terminal domain-containing (BET-containing) proteins (BETPs) such as BRD4 has largely been largely attributed to transcriptional downregulation of cellular anabolic and antiapoptotic processes, but its effect on the bone marrow microenvironment, a sanctuary favoring the persistence of leukemic stem/progenitor cells, is unexplored. Sustained degradation of BETP with the small-molecule BET proteolysis-targeting chimera (PROTAC) ARV-825 resulted in a marked downregulation of surface CXCR4 and CD44, key proteins in leukemia-microenvironment interactions, in acute myeloid leukemia (AML) cells. Abrogation of surface CXCR4 expression impaired SDF-1α-directed migration and was mediated through transcriptional downregulation of PIM1 kinase, which in turn phosphorylates CXCR4 and facilitates its surface localization. Downregulation of CD44, including isoforms CD44v8-10 impaired cystine uptake, lowered intracellular reduced glutathione, and ...
The chemokine receptors CXCR1/2 are involved in a variety of inflammatory diseases, including chronic obstructive pulmonary disease. Several classes of allosteric small-molecule CXCR1/2 antagonists have been developed. The data presented here describe the cellular pharmacology of the acid and ester forms of the nicotinamide glycolate pharmacophore, a potent antagonist of CXCR2 signaling by the chemokines CXCL1 and CXCL8. Ester forms of the nicotinamide glycolate antagonized CXCL1-stimulated chemotaxis (IC50 = 42 nM) and calcium flux (IC50 = 48 nM) in human neutrophils, but they were inactive in cell-free assays of 125I-CXCL8/CXCR2 binding and CXCL1-stimulated guanosine 5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) exchange. Acid forms of the nicotinamide glycolate were inactive in whole-cell assays of chemotaxis and calcium flux, but they inhibited 125I-CXCL8/CXCR2 binding and CXCL1-stimulated [35S]GTPγS exchange. The 3H ester was internalized by neutrophils and rapidly converted to the 3H ...
Plerixafor, also known as AMD3100, is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell (HSC) release from bone marrow and HSC movement into the peripheral circulation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). Plerixafor was approved by the U.S. Food and Drug Administration for this indication on December 15, 2008. In Europe, the drug was approved on 29 May 2009.
TY - JOUR. T1 - Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1. AU - Rossi, O.. AU - Karczewski, J.. AU - Stolte, E.H.. AU - Brummer, R.J.. AU - van Nieuwenhoven, M.A.. AU - Meijerink, M.. AU - van Neerven, R.J.J.. AU - van Ijzendoorn, S.C.. AU - van Baarlen, P.. AU - Wells, J.. PY - 2013. Y1 - 2013. N2 - BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical ...
The CXCR3 receptor has been identified as the gateway for permiability in celiac disease. A study published in the July issue of Gastroenterology identifies the CXCR3 receptor in the intestine as a gluten gateway. When people with celiac disease eat ...
The chemokine CXCL12/SDF1a has first been described in the immune system where it functions include chemotaxis for lymphocytes and macrophages, migration of hematopoietic cells from fetal liver to bone marrow and the formation of large blood vessels. Among other chemokines, CXCL12 has recently attracted much attention in the brain as it has been shown that it can be produced not only by glial cells but also by neurons. In addition, its receptors CXCR4 and CXCR7, which are belonging to the G-protein coupled receptors family, are abundantly expressed in diverse brain area, CXCR4 being a major co-receptor for human immunodeficiency virus (HIV)-1 entry. This chemokine system has been shown to play important roles in brain plasticity processes occurring during development but also in the physiology of the brain in normal and pathological conditions. For example, in neurons, CXCR4 stimulation has been shown regulate the synaptic release of glutamate and GABA. It can also act post-synaptically by activating a
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These co-receptors are chemokine receptors CCR5 or CXCR4. Following a structural change in another viral protein (gp41), HIV ... CD4 is a co-receptor of the T cell receptor (TCR) and assists the latter in communicating with antigen-presenting cells. The ... The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host ... Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (July 1988). "The CD4 receptor is complexed in detergent lysates to ...
"Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells". The Journal of Clinical Investigation. ... These receptors belongs to the G protein-coupled seven-transmembrane receptors. CCL7 can also interact with cell surface ... C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3". The Journal ... "Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling". Journal of ...
September 2009). "A functional heteromeric MIF receptor formed by CD74 and CXCR4". FEBS Letters. 583 (17): 2749-57. doi:10.1016 ... Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair ... Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair ... Farr L, Ghosh S, Moonah S (2020). "Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair ...
"The chemokine SDF-1alpha triggers CXCR4 receptor dimerization and activates the JAK/STAT pathway". FASEB Journal. 13 (13): 1699 ... In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and ... "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 ... "Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 ...
A CXCR4 agonist pepducin mobilizes bone marrow hematopoietic cells. A PAR1 pepducin, PZ-128, has successfully completed phase I ... Pepducins employ lipidated fragments of intracellular G protein-coupled receptor loops to modulate GPCR action in targeted cell ... "Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cells". 2010. Archived from the original on 2011 ... Kuliopulos A, Covic L (December 2003). "Blocking receptors on the inside: pepducin-based intervention of PAR signaling and ...
Mostashari-Rad, T; Arian, R; Mehridehnavi, A; Fassihi, A; Ghasemi, F (June 13, 2019). "Study of CXCR4 chemokine receptor ... However, dealing with receptor flexibility in docking methodologies is still a thorny issue. The main reason behind this ... If the protein is a receptor, ligand binding may result in agonism or antagonism. Docking is most commonly used in the field of ... Wei BQ, Weaver LH, Ferrari AM, Matthews BW, Shoichet BK (Apr 2004). "Testing a flexible-receptor docking algorithm in a model ...
CXCR4, previously called LESTR or fusin, is the receptor for CXCL12. This CXCL12-CXCR4 interaction used to be considered ... For instance, blocking CXCR4, the receptor for CXCL12, with Plerixafor (AMD-3100) increased the effectiveness of combretastatin ... it was suggested that CXCL12 may also bind the CXCR7 receptor (now called ACKR3). By blocking CXCR4, a major coreceptor for HIV ... "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer ...
"Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling ... 2005). "A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid". Proceedings of the National ... Gambogic acid inhibits such osteoclastogenesis by inhibiting CXCR4 signaling pathways. Gambogic acid has also been found to ... a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-kappaB ...
Ghosh S, Preet A, Groopman JE, Ganju RK (July 2006). "Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis ... Its affinity for CB2 receptors is 13.8 nM, while its affinity for CB1 is 383 nM, meaning that it binds almost 28 times more ... In the United States, all CB1 receptor agonists of the 3-(1-naphthoyl)indole class such as JWH-015 are Schedule I Controlled ... Marriott KS, Huffman JW (2008). "Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor". ...
Lee, JH; Park, JW; Kim, SW; Park, J; Park, TS (15 December 2017). "C-X-C chemokine receptor type 4 (CXCR4) is a key receptor ... the PGCs express two CXCR4 transmembrane receptor proteins. The signaling system involving this protein and its ligand, Sdf1, ... The CXCR4/Sdf1 system is also used, though may not be the only method necessary. In the mouse, primordial germ cells (PGCs) ... There is also evidence for the CXCR4/Sdf1 system in frogs.[citation needed] In birds, the PGCs arise from the epiblast and ...
A focus on the CCR5 co-receptor as a potential target for anti-HIV medications began in 1996 with the discovery of CCR5-Δ32, or ... X4 virus, or T-tropic HIV-1, targets T-cells and uses CXCR4 as the coreceptor. Dual-tropic strains of HIV-1, which utilize both ... However, viral changes from CCR5 to CXCR4 coreceptor usage have been associated with a faster rate of CD4+ T-cell loss, rapid ... The two coreceptors involved in the entry of HIV-1, CCR5 and CXCR4, belong to the larger family of 7-transmembrane segment (7TM ...
"Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease". Nat. ... A gain-of-function mutation resulting in a truncated form of CXCR4 is believed to be its cause. The truncated form of the ... receptor has a 2-fold increase in G-protein coupled intracellular signalling, and this mutation of the receptor can be ...
Moreover, inhibition of the CXCR4 receptor reduced metastatic potential without altering tumorigenic capacity. In breast cancer ... The cell surface receptor interleukin-3 receptor-alpha (CD123) is overexpressed on CD34+CD38- leukemic stem cells (LSCs) in ... In the invasive edge of pancreatic carcinoma, a subset of CD133+CXCR4+ (receptor for CXCL12 chemokine also known as a SDF1 ... These cells exhibited significantly stronger migratory activity than their counterpart CD133+CXCR4− cells, but both showed ...
For example, suppression of chemokine receptors (CXCR4 and CCR5) on host cells can prevent HIV viral entry. While traditional ... which cause the release pattern recognition receptors (PRRs). These receptors help in labeling which pathogens are viruses, ... Lapteva N, Yang AG, Sanders DE, Strube RW, Chen SY (January 2005). "CXCR4 knockdown by small interfering RNA abrogates breast ... Crowe S (2003). "Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication, ...
CXCR4 and CXCR7, can be used as molecular prognosis factors. People who express low levels of both chemokine receptors have the ... Retrospective research showed that two chemokine receptors, ...
1999). "Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4". Developmental Biology. 213 (2): 442- ... the interaction between the chemokine CXCL12 expressed by stromal cells and its receptor CXCR4 expressed on HSCs has been ... 1991). "The kit receptor and its ligand, steel factor, as regulators of hematopoiesis". Cancer Cells. 3 (12): 480-487. PMID ... It has also been found that calcium ions can act as chemotactic signals to HSCs via the G protein-coupled receptor (GPCR) ...
M-tropic HIV-1 isolates that use only the CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that ... on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4, but others are known to ... replicate in primary CD4+ T cells as well as in macrophages and use the α-chemokine receptor, CXCR4, for entry. Dual-tropic HIV ... exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This ...
mineralocorticoid receptor activity. • steroid binding. • G-protein coupled receptor activity. • steroid hormone receptor ... Catusse J, Wollner S, Leick M, Schröttner P, Schraufstätter I, Burger M (November 2010). "Attenuation of CXCR4 responses by ... Receptor/signaling modulators. Estrogens and antiestrogens. Androgen receptor modulators. Progesterone receptor modulators. ... G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans ...
"The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein-coupled receptor CXCR4". Mol. Biol. Cell. 25 (12): ...
CD4 receptor) on the target cell. Then the virus binds to the chemokine coreceptors CXCR4 or CCR5, resulting in conformational ... and specific host-cell surface receptors (e.g. ...
An exception to this is a small minority of viruses that use alternate receptors, such as CXCR4 or CCR2. Those individuals who ... Alkhatib G (March 2009). "The biology of CCR5 and CXCR4". Current Opinion in HIV and AIDS. 4 (2): 96-103. doi:10.1097/COH. ... mutation on the CCR5 receptor. This mutation, found at relatively high frequencies in Northern Europeans (16%), results in a ...
It may be mediated by interaction through CXCR4 (CD184) the receptor for CXC Chemokines (e.g., SDF1) and α4β1 integrins. ... Burger JA, Spoo A, Dwenger A, Burger M, Behringer D (August 2003). "CXCR4 chemokine receptors (CD184) and alpha4beta1 integrins ...
... results from autosomal dominant mutations in the gene for the chemokine receptor, CXCR4, resulting in a carboxy- ... 2011). "AMD3100 is a potent antagonist at CXCR4(R334X), a hyperfunctional mutant chemokine receptor and cause of WHIM syndrome ... May 2003). "Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency ... The truncation of the receptor protein results in the inability of downregulation after stimulation. Thus, the receptor remain ...
... a selective CXCR4 receptor inhibitor, in HIV-1 infection". Journal of Acquired Immune Deficiency Syndromes. 37 (2): 1253-62. ...
... and HIV co-receptor activity. HIV-1 most commonly uses the chemokine receptors CCR5 and/or CXCR4 as co-receptors to enter ... Though it lacks the unique structure of a chemokine, it is still capable of binding to the CCR5 and CXCR4 chemokine receptors. ... It is a G protein-coupled receptor which functions as a chemokine receptor in the CC chemokine group. CCR5's cognate ligands ... Cutler CW, Jotwani R (2006). "Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of ...
CXCL12 binds the receptor CXCR4 actively counteracting apoptosis and recruiting progenitor cells to the site of injury. mir-126 ...
Cleavage of SDF-1 reduces it heparan sulfate affinity and interactions with its receptor CXCR4 are reduced. The ADAM family of ... or cleavage and release of receptors. Release of the receptor may also generate soluble receptors which act as decoys by ... The ephrins EPH receptor A2 and A3 are shed by ADAM10, creating cleaved soluble Eph receptors, which inhibit tumor angiogenesis ... such as VE-cadherin and kinase insert domain receptor (KDR, VEGF receptor 2) which aid in influencing the progression of ...
The presence of a co-receptor, CXCR4, is sufficient for this mutant strain to infect human cells. The strain with this ... the glycoprotein gp120 binds to the CD4 receptor on any target cell that has such a receptor, particularly the helper T-cell. ... Since CD4 receptor binding is the most obvious step in HIV infection, gp120 was among the first targets of HIV vaccine research ... This membrane receptor was isolated from Rauscher murine leukemia virus (R-MuLV). The retroviral protein env has been captured ...
A cellular receptor, generally CCR5 or CXCR4 is required in order for HIV entry into CD4 cells. Cells of individuals homozygous ... HIV binds to immune cell surface receptors, including CD 4 and CXCR4 or CD4 and CCR5. The binding causes conformation changes ...
HIV must bind to a CD4 receptor on a T cell or the CCR5/CXCR4 co-receptors to enter the cell. They can also block the fusion of ...
radiology - randomized trial - rebound - receptor (immunology) - recombinant - recombinant DNA - recombinant DNA technology - ... CXCR4 - cytokines - cytomegalovirus (CMV) - Cytomegalovirus retinitis - cytopenia - cytotoxic - cytotoxic T lymphocyte (CTL) ... co-receptors - coccidioidomycosis - codon - cofactors - cognitive impairment - cohort - colitis - combination therapy - ...
Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, ... transmembrane signaling receptor activity. • tumor necrosis factor-activated receptor activity. • nerve growth factor binding. ... TNFRSF8, CD30, D1S166E, Ki-1, tumor necrosis factor receptor superfamily member 8, TNF receptor superfamily member 8. ...
Chemokine Receptors: CCR5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Seibert C, Sakmar TP (2004). „Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs". Curr. ... Cutler CW, Jotwani R (2006). „Oral mucosal expression of HIV-1 receptors, co-receptors, and alpha-defensins: tableau of ... On je G protein spregnuti receptor[2] koji deluje kao hemokinski receptor u CC hemokinskoj grupi. ...
Mast cells: on their surface express several receptors for chemokines: CCR1, CCR2, CCR3, CCR4, CCR5, CXCR2, and CXCR4. Ligands ... ReceptorsEdit. Further information: Chemokine receptor. Chemokine receptors are G protein-coupled receptors containing 7 ... G proteins are coupled to the C-terminal end of the chemokine receptor to allow intracellular signaling after receptor ... associated with binding receptor and inflammatory chemokines. This often complicates research on receptor-specific therapeutics ...
1997). „Signaling of type II oncostatin M receptor.". J. Biol. Chem. 272 (25): 15760-4. PMID 9188471. doi:10.1074/jbc.272.25. ... Na primer, IL-6 se veže za IL-6 receptor. Kompleks ova dva proteina se onda asocira sa gp130. Taj kompleks od 3 proteina se ... 1999). „Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis.". Eur. J. ... 1997). „Urokinase receptor is associated with the components of the JAK1/STAT1 signaling pathway and leads to activation of ...
G-protein coupled receptor activity. • chemokine receptor activity. • interleukin-8 receptor activity. • signal transducer ... G-protein coupled receptor signaling pathway. • cell surface receptor signaling pathway. • receptor internalization. • ... Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by ... "Chemokine Receptors: CXCR1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
... suppression of chemokine receptors (CXCR4 and CCR5) on host cells can prevent HIV viral entry.[153] ... which cause the release pattern recognition receptors (PRRs).[167] These receptors help in labeling which pathogens are viruses ... Crowe S (2003). "Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication, ... "CXCR4 knockdown by small interfering RNA abrogates breast tumor growth in vivo". Cancer Gene Therapy. 12 (1): 84-9. doi ...
By antagonizing the CXCR4 receptor, Tat also appears to selectively encourage the reproduction of less virulent M-tropic ( ... which use the CXCR4 receptor) to emerge later after mutating from M-tropic strains.[5] ... macrophage-tropic) strains of HIV (which use the CCR5 receptor) early in the course of infection, allowing the more rapidly ... "Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1". Proc. Natl. Acad. Sci. U.S. ...
CXCR4. *Agonists: MIF. *SDF-1 (CXCL12). *Ubiquitin. *Antagonists: Plerixafor (AMD3100). *Antibodies: Ulocuplumab (against CXCR4 ... chemokine receptor activity. • receptor activity. • protein binding. • C-C chemokine receptor activity. • C-C chemokine binding ... Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene.[5] CCR6 ... "Chemokine Receptors: CCR6". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
Znaczenie CD4 polega również na tym, że jest to jeden z receptorów (oprócz koreceptorów, którymi są receptory chemokin: CXCR4 i ... Altered proximal T cell receptor (TCR) signaling in human CD4+CD25+ regulatory T cells.. „J Leukoc Biol". 80 (1), s. 145-51, ... Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody.. „Nature". ... Constitutively active Lck kinase in T cells drives antigen receptor signal transduction.. „Immunity". 32 (6), s. 766-77, Jun ...
Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are ... CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the ...
transmembrane signaling receptor activity. • MHC class II protein binding. Cellular component. • membrane. • external side of ... Institute for Vaccine Research in the UK demonstrated that LAG-3 participates in Treg-induced upregulation of CCR7 and CXCR4 on ... cell surface receptor signaling pathway. • positive regulation of natural killer cell mediated cytotoxicity. • antigen ... It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies ...
Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A ... Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. ... TNFRSF1 (CD120) • TNFRSF1A (CD120a) • TNFRSF1B (CD120b) • TNFRSF3 (Limfotoksin beta receptor) • TNFRSF4 (CD134) • TNFRSF5 (CD40 ... Update on chemokine receptor nomenclature". Pharmacol. Rev. 54 (2): 227-9. DOI:10.1124/pr.54.2.227. PMID 12037138. ...
Coakley, E., Petropoulos, C. J. and Whitcomb, J. M. (2005) Assessing chemokine co-receptor usage in HIV. Curr Opin Infect Dis. ... Xiao, H., Neuveut, C., Tiffany, H. L., Benkirane, M., Rich, E. A., Murphy, P. M. and Jeang, K. T. (2000) Selective CXCR4 ...
Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... The interferon-α/β receptor (IFNAR) is a virtually ubiquitous membrane receptor which binds endogenous type I interferon (IFN) ... or it can result in recycling of the receptor without an extended impact on membrane receptor levels.[2] However, clathrin- ... or a sequence of conserved amino acids that are involved in binding to the receptor, specifically the high affinity receptor ...
CXCR4+SSEA-1+Oct-4+ stem cells identified in adult bone marrow". Leukemia. 20 (5): 857-869. doi:10.1038/sj.leu.2404171. PMID ... such as receptors) and their associated proteins between the daughter cells.[3] ...
... activates Tpo receptor expression and interacts with GATA1 protein". Oncogene. 21 (43): 6669-79. doi:10.1038/sj.onc.1205884. ... "CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin". Journal of ... and megakaryocytes in peroxisome proliferator activator receptor-binding protein (PBP) null embryos implicate GATA family of ...
The receptor belongs to the type I cytokine receptor family and is a heterodimer with a unique alpha chain paired with the ... The interleukin-3 receptor (CD123) is a molecule found on cells which helps transmit the signal of interleukin-3, a soluble ... The receptor, found on pluripotent progenitor cells, induces tyrosine phosphorylation within the cell and promotes ... The gene coding for the receptor is located in the pseudoautosomal region of the X and Y chromosomes. ...
Perhaps this is because immunoglobulins inhibit the cardiac autoantibodies by competing for Fc receptors. Alternatively, the ... CCR5 or CXCR4, by entry into cardiomyocytes (after binding to ganglioside GM1), or through TNF-α. In addition, HIV-1-associated ... Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion and death receptor- ... Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion and death receptor- ...
... interleukin 1 receptor-like 1 (IL1RL1), and interleukin 18 receptor 1 (IL18R1), form a cytokine receptor gene cluster in a ... interleukin-1, Type I, activating receptor activity. • interleukin-1 receptor activity. Cellular component. • integral ... This gene and four other interleukin 1 receptor family genes, including interleukin 1 receptor, type I (IL1R1), interleukin 1 ... Interleukin-1 receptor-like 2 is a protein that in humans is encoded by the IL1RL2 gene.[5][6][7][8] ...
Binding of growth hormone to the receptor leads to receptor dimerization (the receptor may however also exist as a pre- ... receptor complex. • integral component of plasma membrane. • extracellular region. • cell surface. • growth hormone receptor ... 2aew: A model for growth hormone receptor activation based on subunit rotation within a receptor dimer ... Growth hormone receptor has been shown to interact with SGTA,[8] PTPN11,[9][10] Janus kinase 2,[11][12][13] Suppressor of ...
CD4 se veže na beljakovini gp120 in P4HB/PDI virusa HIV in predstavlja sestavni del kompleksa P4HB/PDI-CD4-CXCR4-gp120. CD4 ... Pri tem se CD4 z zunanjim delom veže na določeno mesto molekule PHK II, ki je oddaljeno od vezavnega mesta za receptor ...
... is a type II cytokine receptor. It binds to Interleukin-22. It is a heterodimer of α1[1] and IL-10Rβ2[1 ... Receptors,+Interleukin-22 at the US National Library of Medicine Medical Subject Headings (MeSH) ... a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R". J. Biol. Chem. 275 (40 ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Interleukin-22_receptor&oldid=723692207" ...
Veže se na beljakovinski receptor CCR5, ki se nahaja na površini celic v telesu, ki je okuženo s HIV. Virus HIV se pripne na to ... Maravirok je učinkovit le tedaj, ko je bolnik okužen z virusom, ki nima sposobnosti vezave na CXCR4. Zato je pred uporabo ... Z vezavo maraviroka na receptor CCR5 se virus ne more pripeti na celico in posledično se prepreči tudi njegov vstop v človeške ... Biswas P, Tambussi G, Lazzarin A (2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert ...
Chan C.C., Shen D., Hackett J.J., Buggage R.R., Tuaillon N. Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines ... G-protein coupled receptor activity. • связывание с белками плазмы. • signal transducer activity. • C-C chemokine receptor ... CXCR5, BLR1, CD185, MDR15, C-X-C motif chemokine receptor 5, C-X-C chemokine receptor type 5. ... Howard O.M., Dong H.F., Su S.B., Caspi R.R., Chen X., Plotz P., Oppenheim J.J. Autoantigens signal through chemokine receptors ...
Clapham PR, McKnight A. (2001). "HIV-1 receptors and cell tropism". Br Med Bull. 58 (4): 43-59. doi:10.1093/bmb/58.1.43. PMID ... Ang α-chemokine SDF-1 na ligando CXCR4 ay sumusupil ng replikasyon ng mga hiwalay na T-tropic HIV-1. Ginagawa nito ito sa ... Ang HIV na tanging gumagamit ng reseptor na CCR5 ay tinatawag R5; ang mga tanging gumagamit ng CXCR4 ay tinatawag na X4, at ang ... Coakley, E., Petropoulos, C. J. and Whitcomb, J. M. (2005). "Assessing ch vbgemokine co-receptor usage in HIV". Curr. Opin. ...
Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A ... evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation.". Glia 41 (4): 354-70. PMID 12555203. doi: ... GPR15, G-protein spregnuti receptor 15, je protein koji je kod čoveka kodiran GPR15 genom.[1][2] ... Deng HK, Unutmaz D, KewalRamani VN, Littman DR (1997). "Expression cloning of new receptors used by simian and human ...
Receptor[уреди]. Receptor za ovaj hemokin je CXCR4, koji je ranije bio nazivan fuzin.[13] CXCL12-CXCR4 interakcija je nekad ... 2007). „Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in ... ćelije raka koje izražavaju CXCR4 receptor privučene ka metastaznim ciljnim tkivima koja oslobađaju ligand, CXCL12.[10] Kod ... G-protein spregnuti receptor proteinski signalni put. • interćelijska signalizacija. • cirkulacija. • regulacija aktin ...
Current investigations show that chemokine receptor CXCR4 is functionally expressed on a multitude of tissues and cell types, ... CXCR4: chemokine receptor extraordinaire Immunol Rev. 2000 Oct;177:175-84. doi: 10.1034/j.1600-065x.2000.17715.x. ... Current investigations show that chemokine receptor CXCR4 is functionally expressed on a multitude of tissues and cell types, ... In 1996 CXCR4 was discovered as one of the co-factors required for supporting T-lymphocyte tropic HIV infection into permissive ...
A 1.9 kb transcript was cloned from cultured bovine aortic (BAEC) and human umbilical vein endothelial cells (HUVEC). CXCR4 ... The expression of chemokine receptor and viral coreceptor CXCR4 is reported in cultured endothelial cells and in arterial ... Chemokine receptor CXCR4 expression in endothelium Biochem Biophys Res Commun. 1998 Jan 6;242(1):46-53. doi: 10.1006/bbrc. ... The expression of chemokine receptor and viral coreceptor CXCR4 is reported in cultured endothelial cells and in arterial ...
Consequences of ChemR23 heteromerization with the chemokine receptors CXCR4 and CCR7.. de Poorter C1, Baertsoen K, Lannoy V, ... Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative ... The functional responses of CHO-K1 cells expressing CXCR4 (C), ChemR23 (E) or both receptors (D, F) were measured by using the ... The functional responses of CHO-K1 cells expressing ChemR23 (▪), CXCR4 (•), CCR7 (♦), ChemR23 + CXCR4 (□) or ChemR23 + CCR7 ...
The CCR5 and CXCR4 Coreceptors Are Both Used by Human Immunodeficiency Virus Type 1 Primary Isolates from Subtype C Tonie ... Expression of CXCR4 on Feline Peripheral Blood Mononuclear Cells: Effect of Feline Immunodeficiency Virus Infection Brian J. ... Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4+ Mature Thymocytes Correlates with Their Capacity ... Identification of gp120 Binding Sites on CXCR4 by Using CD4-Independent Human Immunodeficiency Virus Type 2 Env Proteins George ...
CCR5, CXCR4, and CD4 Are Clustered and Closely Apposed on Microvilli of Human Macrophages and T Cells Irwin I. Singer, Solomon ... CXCR4 Is Down-Regulated in Cells Infected with the CD4-Independent X4 Human Immunodeficiency Virus Type 1 Isolate m7NDK Susana ... CD4-Independent Infection of Two CD4−/CCR5−/CXCR4+ Pre-T-Cell Lines by Human and Simian Immunodeficiency Viruses Alessandra ... Characterization of Chemokine Receptor Utilization of Viruses in the Latent Reservoir for Human Immunodeficiency Virus Type 1 ...
Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in different cell types ( ... Regulation of the Chemokine Receptor CXCR4 by Hypoxia. Tiziana Schioppa, Badarch Uranchimeg, Alessandra Saccani, Subhra K. ... Hyp-increased CXCR4 Expression in Cancer Cells.. Chemokine receptors may act as molecular tools exploited by cancer cells to ... The involvement of CXCR4 in cancer metastasis has been proposed by Muller and colleagues, who showed that this receptor and its ...
Thus, AMD3100 prevents CXCR4 functioning as both a HIV-1 co-receptor and a CXC-chemokine receptor. Development of small ... AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor.. Donzella GA1, Schols D, Lin SW, Esté JA, ... The bicyclam AMD3100 (formula weight 830) blocks HIV-1 entry and membrane fusion via the CXCR4 co-receptor, but not via CCR5. ... AMD3100 prevents monoclonal antibody 12G5 from binding to CXCR4, but has no effect on binding of monoclonal antibody 2D7 to ...
Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and ... Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels ...
while its receptor CXCR4 was significantly lower (. ) in EC patients compared to healthy controls. The concentrations of ... The AUC of CXCR4 (0.6456; ) was similar to AUC for CXCL12 (0.6354; ) and CEA (0.6973; ) and higher than that for SCC-Ag (0.5384 ... CXCR4 (AUC = 0.6456; ), and classical tumor markers-CEA (AUC = 0.6973; ) and SCC-Ag (AUC = 0.5384; ) as well as CRP (AUC = ... Table 3: Diagnostic criteria for chemokine CXCL12 and its receptor (CXCR4), classical tumor markers (CEA and SCC-Ag), and C- ...
The gp120-induced mucus formation was blocked by the inhibitors of CXCR4, α7-nicotinic acetylcholine receptor (α7-nAChR), and γ ... We found that NHBE cells expressed the HIV-coreceptor CXCR4 but not CCR5 and produced mucus in response to CXCR4-tropic gp120. ... for the first time that HIV-gp120 induces and regulates mucus formation in the airway epithelial cells through the CXCR4-α7- ... acid (GABA)AR but not the antagonists of CCR5 and epithelial growth factor receptor (EGFR). These results identify two distinct ...
CCR5 or CXCR4. 1, 2, 3, 4 As a key co-receptor, CXCR4 thus takes an important role in the HIV-1 infection. In fact, CXCR4 is ... Anti-CXCR4 mAb molecules were covalently bound on the metal nanoshells for immuno-reactions with the CXCR4 receptors on the CEM ... 30 CXCR5 receptors. In addition, the CXCR4 receptors are estimated to distribute on ~70% area of the cell surface.. ... which further confirms that anti-CXCR4 mAb-Ag complexes were principally conjugated with the target sites of CXCR4 receptors on ...
We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. Strong cytoplasmic CXCR4 staining was more ... We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. Strong cytoplasmic CXCR4 staining was more ... high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4 ... High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, ...
Kinetic analysis of the early signaling steps of the human chemokine receptor CXCR4 View in MDC Repository ... We show that CXCR4 presents a multifaceted response to CXCL12, with receptor activation (≈0.6s) followed by a rearrangement in ... We demonstrate that CXCR4 exhibits a multifaceted response that involves dynamic receptor dimer rearrangements, which is ... Here, we investigate the kinetics and dynamics of the activation and early signaling steps of the chemokine receptor CXCR4 in ...
Aim The purpose of this study was to determine CXCR4 gene expression in peripheral blood and bone marrow of NHL patients before ... After chemotherapy, significant decrease in CXCR4 expression was observed. Bone marrow: 3 AU-5 pts, 2 AU-7 pts, 1 AU-5 pts, 0 ... in the level of CXCR4 expression was found in reactive lymph nodes compared to lymphoma samples We observed high level of CXCR4 ... Conclusions Decrease in CXCR4 expression in the bone marrow of NHL patients after chemotherapy may be a good prognostic factor. ...
Abstract:The C-X-C chemokine receptor-4(CXCR4) is a G-protein coupled receptor (GPCR) which belongs to the family I GPCR or ... The C-X-C chemokine receptor-4(CXCR4) is a G-protein coupled receptor (GPCR) which belongs to the family I GPCR or rhodopin- ... Recently, crystal structure of human CXCR4 receptor was reported, which facilitates the structure-based drug discovery of CXCR4 ... Recently, crystal structure of human CXCR4 receptor was reported, which facilitates the structure-based drug discovery of CXCR4 ...
HIV co-receptor downregulation as antiviral principle: SDF-1α-dependent internalization of the chemokine receptor CXCR4 ... have high levels of the chemokine receptor CXCR4. Sustained expression of CXCR4 was maintained on synovial T cells by specific ... functionally relevant levels of the chemokine receptor CXCR4. This constitutive chemokine receptor was previously reported to ... The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow ...
The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial ... The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial ... The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial ... The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial ...
Differential Functional Activation of Chemokine Receptor CXCR4 Is Mediated by G Proteins in Breast Cancer Cells. Jane D. ... CXCR4 expression in a panel of human breast cancer cell lines. A, Western blot analyses of CXCR4 in whole cell lysates. β-Actin ... MDA-MB-231/CXCR4 siRNA knockdown cell line was included as control for antibody specificity. The histograms in the CXCR4 siRNA ... Differential Functional Activation of Chemokine Receptor CXCR4 Is Mediated by G Proteins in Breast Cancer Cells ...
... and the CXCR4/CXCL12 axis has been shown to activate cell cycle progression and malignant cell migration through stimulation of ... Dysregulation of the chemokine receptor CXCR4 is relevant in melanoma progression, ... Dysregulation of the chemokine receptor CXCR4 is relevant in melanoma progression, and the CXCR4/CXCL12 axis has been shown to ... Correlation of chemokine receptor CXCR4 mRNA in primary cutaneous melanoma with established histopathologic prognosticators and ...
Role of chemokine receptors CXCR4 and CXCR7 for platelet function. Madhumita Chatterjee, Dominik Rath, Meinrad Gawaz ... Role of chemokine receptors CXCR4 and CXCR7 for platelet function Message Subject (Your Name) has forwarded a page to you from ... This review summarizes the relative expression of CXC chemokine receptor 4 (CXCR4) and CXCR7 in platelets, their dynamic ... Platelet CXCR4-CXCR7 expression contributing to clinical prognosis. *Differential involvement of CXCR4-CXCR7 in modulating ...
... chemokines and their receptors (Melillo at al., 2005). One of the chemokine receptors we identified, CXCR4, is frequently up- ... We identified, as transcriptional targets of CXCR4/SDF-1α, two tyrosine-kinase receptors: TYRO3 and AXL. These proteins belong ... Avilla, Elvira (2009) Functional role of the CXCR4 chemokine receptor in thyroid cancer. [Tesi di dottorato] (Inedito) ... Thyroid cancer;chemokine receptors;tyrosine kinase receptors.. Settori scientifico-disciplinari del MIUR:. Area 06 - Scienze ...
Zhang H, Zhang L, Chen L, Li W, Li F, Chen Q. Stromal Cell-derived Factor-1 and its Receptor CXCR4 are Upregulated Expression ... Stromal Cell-derived Factor-1 and its Receptor CXCR4 are Upregulated Expression in Degenerated Intervertebral Discs Hua Zhang1 ... Background: Although chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 induce degradation of articular ... Conclusions: Our findings suggest upregulated expression of SDF-1 and its receptor CXCR4 in degenerated IVD. ...
CXCR4 belongs to the superfamily of G protein-coupled receptors (GPCR). CXCR4 is constitutively expressed in a wide variety of ... β-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this ... The receptor is also involved in HIV infection and tumor growth and metastasis. Antagonists of CXCR4 have been widely evaluated ... 3A and B). These data indicate that bryostatin-5 inhibits SDF-1-mediated chemotaxis not by blocking the CXCR4 receptor but by ...
CXCR4-2/IT1t, P21), 3OE0 (CXCR4-3/CVX15, C2), 3OE8 (CXCR4-2/IT1t, P1), 3OE9 (CXCR4-3/IT1t, P1), 3OE6 (CXCR4-1/IT1t, I222). ... CXCR4-1, CXCR4-2 and CXCR4-3 were co-crystallized with IT1t (two crystal forms for CXCR4-2), while crystals of CXCR4-3 were ... Dimer interactions in CXCR4-2/IT1t and CXCR4-3/CVX15. (A) Molecular surface representation of the CXCR4 dimer in CXCR4-2/IT1t ( ... CXCR4-1 and CXCR4-2 display lower binding affinity for the CVX15 peptide compared to CXCR4-WT and CXCR4-3. Calcium flux assays ...
CXCR4 upregulation is an indicator of sensitivity to B-cell receptor/PI3K blockade and a potential resistance mechanism in B- ... CXCR4 upregulation is an indicator of sensitivity to B-cell receptor/PI3K blockade and a potential resistance mechanism in B- ... Physiologically, the CXCR4 chemokine receptor binds to SDF-1αand plays a critical role in the chemotaxis of normal germinal ... Figure 6.Model for B-cell receptor/SYK/PI3K regulation of CXCR4 signals. Red arrows indicate consequences of spleen tyrosine ...
To examine the expression of the stromal cell-derived factor 1 (SDF-1)/CXCR4 receptor ligand system in pancreatic cancer cells ... The results indicate that the paracrine mechanism is involved in the SDF-1/CXCR4 receptor ligand system in pancreatic cancer. ... Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression ... Expression of Stromal Cell-derived Factor 1 and CXCR4 Ligand Receptor System in Pancreatic Cancer: A Possible Role for Tumor ...
The purpose of this study is to investigate the relationship between SDF-1/CXCR4 and metastasis of laryngeal and hypopharyngeal ... Most of the chemokine receptors interact with pleural ligands, and vice. versa, but the SDF-1/CXCR4 receptor ligand system has ... there is a diversity of views on the role of the SDF-1/CXCR4 receptor ligand system in. malignant tissues. And such studies are ... We hypothesized that SDF-1/CXCR4 (ligand/receptor) system plays an important role in. laryngeal and hypopharyngeal cancer ...
Regulation of expression of stromal-derived factor-1 receptors: CXCR4 and CXCR7 in human rhabdomyosarcomas. Mol Can Res. 2010;8 ... Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease. J ... Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease Kun ... In the present study, we evaluated the expression of two chemokine receptors, CXCR4 and CXCR7, in a series of EMPD patients and ...
These results demonstrate that one mechanism by which US27 can enhance CXCR4 signaling is to alter receptor internalization ... Effect of human cytomegalovirus (HCMV) US27 on CXCR4 receptor internalization measured by fluorogen-activating protein (FAP) ... FAP-tagged CXCR4 and US27 were used to explore receptor internalization and recovery dynamics, and the results demonstrate that ... The US27 protein has no known chemokine ligands but can modulate the signaling activity of host receptor CXCR4. We investigated ...
The chemokine receptor CXCR4, in contrast, is present mainly in highly proliferative and advanced tumors. ... An overexpression of the chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and ... Co-Expression of Somatostatin and CXCR4 Receptors as Targets for Diagnostics and Treatment in Intestinal Neuroendocrine ... 1302 Differential Somatostatin and CXCR4 Chemokine Receptor Expression in Primary Gastroenteropancreatic Neuroendocrine ...
  • Finally, and in contrast to the situation encountered for other previously characterized CXCR4 heteromers, we showed that the CXCR4-specific antagonist AMD3100 did not cross-inhibit chemerin binding in cells co-expressing ChemR23 and CXCR4, demonstrating that cross-regulation by AMD3100 depends on the nature of receptor partners with which CXCR4 is co-expressed. (nih.gov)
  • The CXCR4 antagonist AMD 3100 has been reported to inhibit intracranial growth of primary brain tumors ( 11 ), whereas the antagonist T140 effectively inhibited pulmonary metastasis of human breast cancer cells in SCID mice ( 12 ). (aacrjournals.org)
  • Here we report five independent crystal structures of CXCR4 bound to an antagonist small molecule IT1t and a cyclic peptide CVX15 at 2.5-3.2 Å resolution. (pubmedcentralcanada.ca)
  • Here we report the crystal structures of human CXCR4 in complex with a small molecule antagonist at 2.5 Å resolution and with a cyclic peptide inhibitor at 2.9 Å resolution. (pubmedcentralcanada.ca)
  • In vitro studies demonstrated that SDF-1 significantly increased the migration ability of AsPC-1 and HUVECs, and these effects were inhibited by CXCR4 antagonist T22, and that the coculture system with MRC-9 also increased the migration ability of CFPAC-1 cells, and this effect was significantly inhibited by T22. (aacrjournals.org)
  • D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. (ijbs.com)
  • These data demonstrate that DLS is not the specific and selective antagonist as thought for GHS-R1a and appears to have additional effects on the CXCR4 chemokine receptor. (ijbs.com)
  • This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. (pasteur.fr)
  • These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. (pasteur.fr)
  • Here, we report the crystal structure of the chemokine receptor CXCR4 in complex with the viral chemokine antagonist vMIP-II at 3.1 angstrom resolution. (sciencemag.org)
  • Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection. (mendeley.com)
  • The gp120-induced enhancement of GDPs was blocked by T140, a highly specific antagonist for the chemokine receptor, CXCR4, indicating the involvement of CXCR4 in the gp120-induced increase of GDPs. (nebraska.edu)
  • Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. (physiology.org)
  • The CXCR4-CXCL12 axis regulates the hematopoietic stem cell niche-a property that has led to the approval of the CXCR4 antagonist plerixafor (AMD3100) for mobilization of hematopoietic precursors. (aacrjournals.org)
  • We previously showed that high concentrations of the CXCR4 ligand, wild-type CXCL12 (wtCXCL12), could inhibit colorectal cancer metastasis in vivo , and we have hypothesized that wtCXCL12 dimerizes at high concentration to become a potent antagonist of CXCR4. (aacrjournals.org)
  • These effects were blocked by the specific CXCR4 antagonist AMD3100 and by CXCR4 RNA interference. (unina.it)
  • The specificity of this process was analyzed using several inhibitors of gp120-CD4-CXCR4 interaction. (cnrs.fr)
  • We also previously uncovered some dual CCR5/CXCR4 entrance inhibitors with original non-nucleoside change transcriptase (NNRTI) activity against HIV [37]. (thetechnoant.info)
  • Histone deacetylase inhibitors potently repress CXCR4 chemokine receptor expression and function in acute lymphoblastic leukaemia. (limcr.at)
  • Recent evidence demonstrates that inhibiting CXCR4 signaling restores sensitivity to CTLA-4 and PD-1 checkpoint inhibitors, creating a new line for investigation. (aacrjournals.org)
  • Tck cells also showed an increased chemotactic response to rheumatoid arthritis (RA) fibroblast-like synoviocytes cultured in vitro, which could be blocked using inhibitors against VLA-4 and CXCR4. (ox.ac.uk)
  • All variations exhibited comparable binding in comparison to wild-type CXCR4 (Fig.?3B), suggesting that this ligand binding pocket, although constituting the binding site of little molecule and peptide-based CXCR4 inhibitors, 40,58 isn't mixed up in conversation with MEDI3185. (gasyblog.com)
  • In the present study, we build on these previous results, and investigate the consequences of chemokine receptor heteromerization with ChemR23, the receptor of chemerin, a leukocyte chemoattractant protein structurally unrelated to chemokines. (nih.gov)
  • Chemokines interact with 7 transmembrane domain G-protein-coupled receptors and, so far, 10 CC (CCR1-10), 6 CXC (CXCR1-6), 1 CX3C (CXCR1), and 1 C (XCR1) receptors have been identified ( 9 ). (rupress.org)
  • Chemokines are a family of soluble chemotactic cytokines that bind to their cognate G-protein coupled receptors. (hindawi.com)
  • Chemokines and their receptors play a major role in immune cell trafficking in both physiological and pathological settings ( 1 , 2 ). (frontiersin.org)
  • Chemokines and their receptors determine the distribution of leukocytes within tissues in health and disease. (jimmunol.org)
  • how these receptors differentially mediate the functional and survival response to the chemokines CXCL11, CXCL12 and MIF. (biochemsoctrans.org)
  • We previously found that normal rat thyroid cells, transduced with papillary thyroid cancer (PTC)-related oncogenes, display an inflammatory signature, that includes cytokines, chemokines and their receptors (Melillo at al. (unina.it)
  • Chemokines are produced locally in the tissues and act on target cells through G-protein-coupled receptors, which are characterized structurally by seven transmembrane spanning domains. (knowcancer.com)
  • Reports have suggested that several types of cancer, such as breast, ovary, prostate, kidney, brain, lung, and thyroid, expressed the chemokine receptor and used the chemokines to metastasize to the target organ as in the homing of hematopoietic cells. (knowcancer.com)
  • Chemokines belong to a superfamily of chemo-attracting proteins that bind to chemokine receptors. (jcancer.org)
  • Chemokines are small peptides that are known to exert potent regulatory effects on migration and activation of various immune and non hematopoietic cells via ligation to their seven transmembrane G-protein coupled receptors (GPCRs) [ 1 , 2 ]. (ijbs.com)
  • Chemokines and their receptors control cell migration during development, immune system responses, and in numerous diseases, including inflammation and cancer. (sciencemag.org)
  • The structure helped rationalize a large body of mutagenesis data and together with modeling provided insights into CXCR4 interactions with its endogenous ligand CXCL12, its ability to recognize diverse ligands, and the specificity of CC and CXC receptors for their respective chemokines. (sciencemag.org)
  • Unlike most chemokines whose function and expression are specific and centered around their role in leukocyte trafficking, both stromal cell-derived factor 1/CXCL12 and its first identified receptor CXCR4 were found to be expressed in a wide variety of cell types and tissues ( 3 ). (jimmunol.org)
  • Chemokines and their receptors are postulated to direct migration of distinct leukocyte subsets to sites of inflammation and to their specific niches in lymphoid organs ( 1 , 2 ). (pnas.org)
  • Chemokines and their receptors are important mediators of cell mobilization, recruitment and arrest, and also more broadly induce cell activation by triggering various intracellular signalling tracks. (doabooks.org)
  • Tumor cells can co-opt the promigratory activity of chemokines and their cognate G protein-coupled receptors (GPCRs) to metastasize to regional lymph nodes or distant organs. (sciencemag.org)
  • Unusually for chemokines, SDF-1 and CXCR4 are a relatively "monogamous" ligand-receptor pair (other chemokines tend to use several different chemokine receptors in a fairly "promiscuous" manner). (thefullwiki.org)
  • Chemokines, a family of 8- to 10-kDa chemotactic cytokines, provide signals that guide leukocytes to their appropriate location in the body through transmembrane receptors coupled to heterotrimeric GTP-binding proteins under inflammatory or physiological conditions ( 2 , 31 ). (physiology.org)
  • Chemokines act on chemokine receptors (CKR), members of the seven-transmembrane domain G-protein-coupled receptor (GPCR) superfamily. (aacrjournals.org)
  • A physiological electric field also upregulated expression of CXCR4 and CXCR2 chemokine receptors and upregulated phosphorylation of both chemokines in HUVEC and HMEC cells. (figshare.com)
  • Until recently, SDF-1 and CXCR4 were believed to be a relatively monogamous ligand-receptor pair (other chemokines are promiscuous, tending to use several different chemokine receptors). (wikipedia.org)
  • Chongqian Zhang, Tingjun Hou, Zhiwei Feng and Youyong Li, "Structure-Based Development of Antagonists for Chemokine Receptor CXCR4", Current Computer-Aided Drug Design (2013) 9: 60. (eurekaselect.com)
  • Antagonists of CXCR4 have been widely evaluated for drugs against HIV and tumors. (aacrjournals.org)
  • In an effort to identify novel CXCR4 antagonists, we screened a small library of compounds derived from marine organisms and found bryostatin-5, which potently inhibits chemotaxis induced by SDF-1 in Jurkat cells. (aacrjournals.org)
  • Several HIV-1 chemokine co-receptor antagonists have been recently discovered and are being utilized in human clinical trials [ 5 ]. (ijbs.com)
  • CXCR4 antagonists are as well which the noticed anti-Nef and pro-apoptotic results are chemically tunable. (thetechnoant.info)
  • Collectively, these results recommend our CXCR4 antagonists possess appealing clinical tool for HIV or breasts cancer therapies aswell to be useful probes to examine the hyperlink between CXCR4 and apoptosis. (thetechnoant.info)
  • Herein, we survey that a group of little molecule CXCR4 antagonists can selectively induce apoptosis in MDA-MB-231 breasts cancer tumor cells at sub-nanomolar concentrations. (thetechnoant.info)
  • Our outcomes support a huge body of books that validates CXCR4 being a appealing target for cancers therapy and demonstrate that small-molecule CXCR4 antagonists possess novel therapeutic prospect of HIV an infection beyond their activity against viral entrance by preventing Nef induced T-cell depletion. (thetechnoant.info)
  • Outcomes Selection and natural characterization of energetic CXCR4 antagonists We lately described two group of CXCR4 antagonists and characterized their connections with CXCR4, including their capability to antagonize HIV viral entrance [35, 36]. (thetechnoant.info)
  • Open up in another window Amount 1 Buildings of CXCR4 antagonists found in this research Desk 1 Biological characterization of CXCR4 antagonists 0.05) in accordance with control MDAMB-468: * 4.5E-08, ** 4.2E-08, *** 1.7E-13, **** 6.3E-08, and ***** 3.8E-6, ****** 4.5E-16. (thetechnoant.info)
  • Small-molecule antagonists of CCR5 and CXCR4: a promising new class of anti-HIV-1 drugs. (thefullwiki.org)
  • Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC. (elsevier.com)
  • CXCR4 plays a crucial role as a co-receptor with CCR5 for HIV-1 anchoring to mammalian cell membrane, and is implicated in cancer metastasis and inflammation. (eurekaselect.com)
  • The receptor is also involved in HIV infection and tumor growth and metastasis. (aacrjournals.org)
  • CXCR4 is also involved in the growth and metastasis of various types of cancers. (aacrjournals.org)
  • At least 23 different types of human cancers, including hematopoietic and solid tumors, overexpress CXCR4 ( 7 ), and cancer cells with higher levels of CXCR4 show greater incidence of metastasis ( 8 - 10 ). (aacrjournals.org)
  • Other studies have indicated roles for SDF-1/CXCR4 in the metastasis of neuroblastoma, melanoma, and prostate cancer cells ( 13 - 15 ). (aacrjournals.org)
  • The G protein-coupled chemokine receptor, CXCR4, is specifically implicated in cancer metastasis and HIV-1 infection. (pubmedcentralcanada.ca)
  • CXCR4 has been associated with more than 23 types of cancers where it promotes metastasis, angiogenesis and growth/survival ( 6 - 10 ). (pubmedcentralcanada.ca)
  • High expression of CXCR4 and CXCR7 were both correlated with regional lymph node metastasis and presence of lymphovascular invasion. (jcancer.org)
  • In addition to pathogenesis of HIV, CXCR4 and CCR5 have been implicated in motility, invasion and metastasis of a wide variety of cancer cell types [ 2 , 6 ]. (ijbs.com)
  • Gold Nanoclusters Doped with (64)Cu for CXCR4 Positron Emission Tomography Imaging of Breast Cancer and Metastasis. (semanticscholar.org)
  • This study focuses on novel interactions between highly relevant signaling pathways in breast cancer cells and brain microvascular endothelial cells and may provide insights into the molecular mechanisms of CXCR4/SDF-1α-mediated breast cancer metastasis to the brain. (aacrjournals.org)
  • To examine the prognostic relevance of expression of the chemokine receptors CCR7 and CXCR4 and its ligand CXCL12 in uveal melanoma in nonmetastatic and metastatic patients with correlation to liver metastasis and overall survival. (arvojournals.org)
  • We after that proceeded to exploit the apoptotic kinship between Nef M1 and CXCR4 to suppress the development and metastasis of principal colorectal tumors in mice [31C32] and lately discovered that M1 displays deep anti-proliferative activity against several CXCR4-expressing breasts carcinomas [33C34]. (thetechnoant.info)
  • Indeed, the migration toward SDF-1 (stromal cell-derived factor 1) of tumor cells bearing CXCR4 [chemokine (C-X-C motif) receptor 4] has been implicated in the lymphatic and organ-specific metastasis of various human malignancies. (sciencemag.org)
  • The chemokine CXCL12 and its receptor CXCR4 are implicated in human seminoma metastasis. (edu.au)
  • Fingerprint Dive into the research topics of 'The chemokine CXCL12 and its receptor CXCR4 are implicated in human seminoma metastasis. (edu.au)
  • The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis. (cdc.gov)
  • Evidence suggests that the CXC-chemokine receptor-4 pathway plays a role in cancer cell homing and metastasis, and thus represents a potential target for cancer therapy. (aacrjournals.org)
  • The CXC chemokine receptor-4 (CXCR4) plays a critical role in cancer by positively regulating cancer cell metastasis and survival. (aacrjournals.org)
  • Herein, we show that CXCL122 can not only inhibit implantation of lung metastasis of CXCR4-B16-F10 melanoma cells more effectively than AMD3100, but that CXCL122 also blocks the growth of established pulmonary tumors. (aacrjournals.org)
  • We previously showed that CXCR4 enhances β1 integrin-dependent pulmonary metastasis of B16 melanoma cells 6- to 10-fold following intravenous inoculation ( 4, 5 ). (aacrjournals.org)
  • We also showed that T22, a specific CXCR4 inhibitor, effectively blocked pulmonary dissemination of CXCR4-expressing B16 cells following tail vein inoculation ( 4 ), suggesting that blocking CXCR4 may be an effective strategy for preventing lung metastasis. (aacrjournals.org)
  • Recently, we reported that exogenous administration of CXCL12, the ligand of CXCR4, inhibits colorectal cancer metastasis ( 6 ). (aacrjournals.org)
  • ref. 8 ) and showed that intraperitoneal administration inhibited the metastasis of CXCR4-overexpressing colon cancer cells to the liver ( 6 ). (aacrjournals.org)
  • CXCR4 manages the features of additional immune system and non-immune cells also, and enhances the expansion and/or Mefloquine HCl metastasis of many growth types (6). (az628.com)
  • Many growth cells screen abnormally-elevated cell-surface CXCR4 that contributes to metastasis and expansion (6). (az628.com)
  • Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow. (wikipedia.org)
  • However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 expression is positively correlated with disease free (metastasis free) survival. (wikipedia.org)
  • CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the receptor, CXCR4, is saturated with the ligand produced in an autocrine manner. (wikipedia.org)
  • High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. (frontiersin.org)
  • In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. (frontiersin.org)
  • We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. (frontiersin.org)
  • No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. (frontiersin.org)
  • Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy. (frontiersin.org)
  • CXCR7, an atypical chemokine receptor with a ten times higher affinity for CXCL12 compared to CXCR4, was detected at protein level in ACC metastases and correlated with CXCR4 expression ( 4 ). (frontiersin.org)
  • CXCR7 can generate CXCL12 gradients for CXCR4 but also acts as a CXCL12 "scavenger", as it is constantly recycled to the cell membrane after ligand binding ( 11 , 12 ). (frontiersin.org)
  • We further elaborate and emphasize the prognostic significance of platelet surface expression of CXCR4-CXCR7 in the context of coronary artery disease (CAD). (biochemsoctrans.org)
  • SDF-1α/CXCL12, CXCL11, MIF effects mediated through CXCR4 and CXCR7 may play a regulatory role at the site of vascular and tissue inflammation, immune defence and repair where activated platelets reach as forerunners and function as critical players. (biochemsoctrans.org)
  • However, the potential of the chemokine receptors, CXCR4 and CXCR7, in serving as biomarkers in extramammary Paget's disease (EMPD) has been rarely examined. (jcancer.org)
  • Expressions of CXCR4 and CXCR7 were evaluated in 92 EMPD specimens by immunohistochemistry. (jcancer.org)
  • Both high expression of CXCR4 and CXCR7 were indicative of shorter PFS and CSS. (jcancer.org)
  • In the combined prognostic model, concomitant high expression of CXCR4 and CXCR7 were suggestive of poor prognosis compared with the other two groups. (jcancer.org)
  • Our results demonstrated that CXCR4 and CXCR7 can be used as prognostic biomarkers and prediction of aggressiveness of EMPD. (jcancer.org)
  • Therapy targeting CXCR4 and CXCR7 may helpful to prevent EMPD progression and improve the prognosis of EMPD. (jcancer.org)
  • Expressão de CXCR7 e CXCR4 em em astrocitomas iniltrativos em relação ao tecido cerebral. (usp.br)
  • Recentemente um novo receptor com maior afinidade à CXCL12 foi identificado, o receptor órfão RDC1, agora denominado CXCR7. (usp.br)
  • O objetivo deste estudo é investigar a expressão de mRNA CXCR7 em tecidos astrocitomas difusos e avaliar suas interações com expressão CXCR4 e HIF1alfa, bem como analisar sua relação com mutação do IDH1. (usp.br)
  • Métodos: A expressão do CXCR7, CXCR4, IDH1 e HIF1alfa foram avaliadas por PCR quantitativo em tempo real (qRT-PCR) em 129 amostras congeladas de astrocitomas (25 astrocitoma difuso - AGII, 18 de astrocitoma anaplásico - AGIII e 86 glioblastoma - GBM) e 22 amostras de tecido cerebral não neoplásico (NN) obtidos de cirurgia de epilepsia. (usp.br)
  • A mutação do IDH1 previamente determinada foi analisada em relação aos níveis de expressões de mRNA do CXCR7, CXCR4 e HIF1alfa, combinado com os parâmetros clínico-patológicos e sobrevida global. (usp.br)
  • Nos GBM houve correlação significativa entre CXCR7/CXCR4 (p = 0,002), CXCR7/IDH1 (p (usp.br)
  • Hiperexpressão do HIF1alfa foi associado com maior expressão do CXCR7 e CXCR4 (p = 0,001), enquanto a presença de IDH1 mutado foi associada a menor expressão de mRNA do CXCR7 e CXCR4 (p = 0,009). (usp.br)
  • O nível de expressão do CXCR7 correlacionou-se significativamente com os níveis de expressão do CXCR4 e IDH1 nos AGII e com CXCR4, IDH1 e HIF-1alfa nos GBM. (usp.br)
  • O nível de expressão elevado do CXCR7 e CXCR4 correlacionou-se com nível elevado de expressão de HIF-1a, enquanto a presença da mutação do IDH1 associou-se a níveis reduzidos de CXCR7 e CXCR4. (usp.br)
  • The CXCR7, a recent additional receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. (usp.br)
  • The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytoma tissues and to evaluate its interactions with CXCR4 and HIF1alfa expression and IDH1 mutation. (usp.br)
  • Methods: CXCR7, CXCR4, IDH1 and HIF1alfa expressions were evaluated by quantitative real-time PCR (qRT-PCR) in 129 frozen samples of astrocytoma (25 diffuse astrocytomas - AGII, 18 anaplastic astrocytomas - AGIII and 86 glioblastomas - GBM) and 22 samples of non-neoplastic tissue cerebral (NN) from epilepsy surgery. (usp.br)
  • After PNX, activated platelets stimulate SDF-1 receptors CXCR4 and CXCR7 on pulmonary capillary endothelial cells (PCECs) to deploy the angiocrine membrane-type metalloproteinase MMP14, stimulating alveolar epithelial cell (AEC) expansion and neo-alveolarization. (nature.com)
  • Endothelial-specific ablation of Cxcr4 and Cxcr7 in adult mice similarly impeded lung regeneration. (nature.com)
  • CXCL12 and its receptors, CXCR4 and CXCR7, have been implicated in migration, proliferation and survival of gonocytes and their precursors and progeny, primordial germ cells and spermatogonial stem cells respectively. (edu.au)
  • Prognostic significance of CXCL12, CXCR4, and CXCR7 in patients with breast cancer. (cdc.gov)
  • The homeostatic microenvironment chemokine CXCL12 binds the CXCR4 and CXCR7 receptors, activating divergent signals on multiple pathways, such as ERK1/2, p38, SAPK/JNK, AKT, mTOR, and the Bruton tyrosine kinase (BTK). (aacrjournals.org)
  • Here we document the expression of a second chemokine receptor gene, cxcr7 , in the migrating primordium. (biomedcentral.com)
  • As previously described for other chemokine receptor heteromers, negative binding cooperativity was detected between ChemR23 and chemokine receptors, i.e. the ligands of one receptor competed for the binding of a specific tracer of the other. (nih.gov)
  • We also showed, using mouse bone marrow-derived dendritic cells prepared from wild-type and ChemR23 knockout mice, that ChemR23-specific ligands cross-inhibited CXCL12 binding on CXCR4 in a ChemR23-dependent manner, supporting the relevance of the ChemR23/CXCR4 interaction in native leukocytes. (nih.gov)
  • Recently, expression of CXCR4 was reported in primary tumors and metastatic lesions of patients with ACC both at protein level in vitro and in vivo using radiolabeled CXCR4 ligands ( 3 , 4 ). (frontiersin.org)
  • Here, we investigate the kinetics and dynamics of the activation and early signaling steps of the chemokine receptor CXCR4 in response to its natural ligands CXCL12 and macrophage migration inhibitory factor (MIF), using Förster resonance energy transfer-based approaches. (mdc-berlin.de)
  • Chemokine receptors are G protein-coupled receptors (GPCRs) that, together with their small protein ligands, regulate the migration of many different cell types, most notably leukocytes ( 1 - 3 ). (pubmedcentralcanada.ca)
  • The constructs differ in the precise T4L junction site, the position of the C-terminal truncation, as well as a T240 6.36 P mutation in CXCR4-3, and required further stabilization with ligands to facilitate purification and crystallization. (pubmedcentralcanada.ca)
  • Most of the chemokine receptors interact with pleural ligands, and vice versa, but the SDF-1/CXCR4 receptor ligand system has been shown to involve a one-on-one interaction. (knowcancer.com)
  • The US27 protein has no known chemokine ligands but can modulate the signaling activity of host receptor CXCR4. (physiciansweekly.com)
  • To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this chemokine receptor in rat neurons and astrocytes in vitro. (pasteur.fr)
  • Taken together, the data suggest distinct functions for the two receptors and their ligands in the migration of lymphocyte subsets through lymphoid and nonlymphoid tissues. (pnas.org)
  • This range in activity pays to for probing signaling transduction pathways mediated by CXCR4 and us with a wide set of equipment to review the influence of CXCR4 antagonism against different ligands (such as for example Nef M1 and CXCL12) in a variety of cell types. (thetechnoant.info)
  • This Research Topic will focus on the chemokine receptor CXCR4 and its ligands CXCL12/SDF-1a and macrophage migration inhibitory factor (MIF) in the context of CVD and its link with T2DM and CKD, as well as address dipeptidyl peptidase-4 (DPP4) as an important protease destabilizing CXCL12. (doabooks.org)
  • Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. (medlineplus.gov)
  • Here, we used chimeric G proteins and GPCRs activated solely by artificial ligands to selectively activate the signaling pathways downstream of specific G proteins and showed that CXCR4-mediated chemotaxis and transendothelial migration of metastatic basal-like breast cancer cells required activation of Gα 13 , a member of the Gα 12/13 G protein family, and of the small guanosine triphosphatase Rho. (sciencemag.org)
  • Increased expression of CXCR4 and VLA-4 integrin resulted in concentration-dependent chemotaxis to their ligands, stromal cell-derived factor 1 (SDF-1) and VCAM-1, which could be selectively blocked using a specific CXCR4 inhibitor and antibodies against VLA-4. (ox.ac.uk)
  • Consequently, the Geldanamycin service of CXCR4 could make MSCs migrate to CXCR4 ligands. (welbourneprimary.com)
  • Rho N delays the trafficking of the EGF Receptor to past due endosomes (21) and enhances the lysosomal trafficking of CXCR2 which can be needed for the migration of HEK293 cells towards CXCR2 ligands (22). (az628.com)
  • The variety of motifs leads to co-receptors being able to interact with two to nine different ligands, which themselves can also interact with a number of different co-receptors. (wikipedia.org)
  • CXCR4 mRNA was expressed at high levels in BAEC and HUVEC but was not expressed by cultured bovine arterial smooth muscle cells (BASM) or human umbilical vein smooth muscle cells (HUVSM). (nih.gov)
  • Correlation of chemokine receptor CXCR4 mRNA in primary cutaneous melanoma with established histopathologic prognosticators and the BRAF status. (biomedsearch.com)
  • Studies ascertaining the potential utility of CXCR4 mRNA as a prognosticator in melanoma have focused mainly on metastatic melanoma with conflicting results. (biomedsearch.com)
  • In the light of this, we sought to explore the potential relationship between CXCR4 mRNA expression with established histopathologic prognosticators and BRAF status in melanoma. (biomedsearch.com)
  • Archived consecutive samples (n=107) of primary cutaneous melanoma were retrieved and assessed for the following: CXCR4 mRNA (semiquantitative RT-PCR) and BRAF exon 15 status (DNA Sanger sequencing). (biomedsearch.com)
  • Statistical analyses included correlation between CXCR4 mRNA levels and established histopathologic prognosticators as well as the BRAF status using univariate and multiple linear methods. (biomedsearch.com)
  • Multivariable analyses revealed a significant correlation between elevated CXCR4 mRNA (low ΔCt value) and the presence of BRAF mutation (P=0.02). (biomedsearch.com)
  • Absence of a brisk host response was associated with elevated CXCR4 mRNA expression (P=0.04). (biomedsearch.com)
  • CXCR4 mRNA was significantly lower in AJCC stage 2 compared with stage 1 after controlling for significant clinical prognosticators (P=0.02). (biomedsearch.com)
  • The association between elevated CXCR4 mRNA and absence of a brisk host response suggests that CXCR4 may be involved in regulation of the host immune response in melanoma and is a molecule of potential utility as a biomarker for recruiting melanoma patients for immunotherapy. (biomedsearch.com)
  • Higher CXCR4 mRNA in patients with a BRAF mutation suggests its utility as a putative therapeutic target. (biomedsearch.com)
  • meanwhile, CXCR4 mRNA was detected in all pancreatic cancer tissues, cancer cell lines, and HUVECs. (aacrjournals.org)
  • Recently, several studies have been conducted to detect the mRNA expression of CXCR4 and SDF-1 in solid tumors. (knowcancer.com)
  • Barnard and his colleagues showed the contrary results that CXCR4 mRNA expression was reduced in hepatocellular carcinoma tissue when compared with noncancerous tissue, but was not changed in colon, esophageal, and gastric cancer. (knowcancer.com)
  • The expressions of CXCR4 protein in hucMSC of 2nd-5th passages were detected by flow cytometry , and cxcr4 mRNA levels in hucMSC of 2nd-5th passages were evaluated by real- time quantitative PCR . (bvsalud.org)
  • The cxcr4 mRNA was found in hucMSC of 2nd-5th passages, and expression of cxcr4 of 3rd-5th passages were 0.5585 ± 00875, 0.6205 ± 0.1377, 0.4634 ± 0.0447 times of expression of 2nd passage respectively. (bvsalud.org)
  • It is concluded that the cxcr4 mRNA expresses in hucMSC of 2nd-5th passages, and declines when the number of passages increases. (bvsalud.org)
  • Compared with 2nd passage, cxcr4 mRNA levels in hucMSC of 3rd-5th passages decline, but the expression level of cxcr4 mRNA between hucMSC of 3rd-5th passages is stable. (bvsalud.org)
  • Here, we show that ATC cell lines overexpress CXCR4, both at the level of mRNA and protein. (unina.it)
  • AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. (nih.gov)
  • The bicyclam AMD3100 (formula weight 830) blocks HIV-1 entry and membrane fusion via the CXCR4 co-receptor, but not via CCR5. (nih.gov)
  • AMD3100 prevents monoclonal antibody 12G5 from binding to CXCR4, but has no effect on binding of monoclonal antibody 2D7 to CCR5. (nih.gov)
  • Thus, AMD3100 prevents CXCR4 functioning as both a HIV-1 co-receptor and a CXC-chemokine receptor. (nih.gov)
  • Metal ion enhanced binding of AMD3100 to Asp262 in the CXCR4 receptor. (semanticscholar.org)
  • Plerixafor (AMD3100) is a drug, not yet in routine clinical use, which directly blocks the CXCR4 receptor. (thefullwiki.org)
  • Upon coinjection with 50?g AMD3100, tumor accumulation is reduced to background amounts (Fig.?5b), demonstrating that tumor uptake of [64Cu]NOTA-pentixather is nearly exclusively CXCR4-mediated. (biosweepny.com)
  • Herein, we show that intravenous CXCL12 2 treatment inhibited initial pulmonary dissemination of CXCR4-expressing B16 more effectively than the U.S. Food and Drug Administration (FDA)-approved CXCR4 inhibitor, AMD3100. (aacrjournals.org)
  • Certainly, the CXCR4 little molecule inhibitor AMD3100 didn't impact binding of MEDI3185 to CXCR4 (Fig.?3C). (gasyblog.com)
  • In this study, we have characterized the signaling pathways mediated by CXCR4 in breast cancer cells and its role in breast cancer cell invasion and migration. (aacrjournals.org)
  • CXCR4 involved in several pathways and played different roles in them. (creativebiomart.net)
  • We selected most pathways CXCR4 participated on our site, such as Cytokine-cytokine receptor interaction, Chemokine signaling pathway, Endocytosis, which may be useful for your reference. (creativebiomart.net)
  • In this review collection, current knowledge on molecular aspects of the CXCR4 ligand/receptor family and associated signalling pathways will be discussed. (doabooks.org)
  • After attachment of its ligand, called SDF-1, the CXCR4 protein turns on (activates) signaling pathways inside the cell. (medlineplus.gov)
  • Once signaling is stimulated, the CXCR4 protein is removed from the cell membrane (internalized) and broken down so it can no longer activate the signaling pathways. (medlineplus.gov)
  • 2004). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways. (thefullwiki.org)
  • Here, we review and discuss the most significant findings on the intracellular pathways and on the cross-communication between FPR2 and tyrosine kinase receptors triggered by different FPR2 agonists. (mdpi.com)
  • The CXCL12-CXCR4 axis is the focus of this Molecular Pathways review. (aacrjournals.org)
  • The amino-terminal domain of CXCL12 binds the second extracellular loop of CXCR4 and activates downstream signaling pathways. (aacrjournals.org)
  • CXCL12 binding to CXCR4 triggers multiple signal transduction pathways that are able to regulate intracellular calcium flux, chemotaxis, transcription, and cell survival ( 8 ). (aacrjournals.org)
  • It is speculated this interaction may be through CXCR4 mediated signalling pathways. (wikipedia.org)
  • CXCR4, a classical transmembrane G protein-coupled receptor, has been associated with more aggressive tumor phenotypes and poor prognosis in several cancer types ( 5 - 8 ). (frontiersin.org)
  • Similar to the previously determined high-resolution structures of the β 2 -adrenergic receptor (β 2 AR) ( 17 , 21 ) and A 2A adenosine receptor (A 2A AR) ( 18 ), the CXCR4 constructs contain a T4 lysozyme (T4L) fusion inserted between transmembrane (TM) helices V and VI at the cytoplasmic side of the receptor. (pubmedcentralcanada.ca)
  • Growth hormone secretagogue receptor (GHS-R) belongs to the seven transmembrane GPCR family and serves as an endogenous ligand for the predominantly stomach-derived hormone ghrelin [ 7 , 8 ]. (ijbs.com)
  • SDF-1α interacts specifically with the seven-transmembrane G protein-coupled receptor, CXCR4 ( 15 , 16 ). (aacrjournals.org)
  • CXCR4 is the Gi protein-linked seven-transmembrane receptor for the alpha chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. (pasteur.fr)
  • These functions were studied in a panel of CXCR4 mutants bearing deletions in the NH(2)-terminal extracellular domain (NT) or substitutions in the NT, the extracellular loops (ECL), or the transmembrane domains (TMs). (pasteur.fr)
  • SDF-1 signals through a seven-transmembrane-domain receptor previously known as LESTR/fusin, now designated CXC-chemokine receptor 4 (CXCR4) ( 13 , 14 ). (pnas.org)
  • G protein-coupled receptors , often abbreviated GPCRs, are an abundant superfamily of proteins also known as seven-transmembrane domain receptors , 7TM receptors , 7 pass transmembrane receptors , heptahelical receptors , serpentine receptor , and G protein-linked receptors (GPLRs) . (proteopedia.org)
  • Rhodopsin shares similar membrane topology with the members of the superfamily, specifically family A of the G protein-coupled receptors which include the seven transmembrane helices, an extracellular N-terminus and cytoplasmic C-terminus [4] . (proteopedia.org)
  • The cDNA that imparted this phenotype was found to encode an orphan seven-transmembrane-domain receptor that supported membrane fusion by T cell tropic, but not M tropic, HIV-1 env proteins in a CD4-dependent fashion ( 10 ). (pnas.org)
  • HIV and the 7-transmembrane domain receptors. (thefullwiki.org)
  • The formyl peptide receptor 2 (FPR2) is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR) family. (mdpi.com)
  • a) Three-dimensional representation of human being CXCR4 (PDB Identification quantity 3ODU).40 Residues in transmembrane helices whose part chains donate to the ligand-binding pocket are demonstrated in orange sticks. (gasyblog.com)
  • The CD4 receptor is composed of four concatamerized Ig-like domains and is anchored to the cell membrane by a single transmembrane domain. (wikipedia.org)
  • The diagnostic sensitivity, negative predictive value, and accuracy of CXCR4 were the highest among all analyzed proteins and increased for combined analysis with classical tumor markers and CRP levels. (hindawi.com)
  • CXCR4, one of 19 known human chemokine receptors, is activated exclusively by the chemokine CXCL12 (also known as Stromal Cell-Derived Factor-1, SDF-1) and couples primarily through G i proteins. (pubmedcentralcanada.ca)
  • We investigated the mechanism for enhanced CXCR4 signaling in the presence of US27 using a novel biosensor system comprised of fluorogen activating proteins (FAPs). (physiciansweekly.com)
  • Also, other proteins which involved in the same pathway with CXCR4 were listed below. (creativebiomart.net)
  • G protein-coupled receptors are cell surface signalling proteins involved in many physiological functions and in multiple diseases. (proteopedia.org)
  • The results implicate the involvement of multiple CXCR4 domains in HIV-1 coreceptor function, especially the second extracellular loop, though the structural requirements for coreceptor function were somewhat variable for different env proteins. (pnas.org)
  • Finally, a hybrid receptor in which the amino terminus of CXCR4 was replaced by that of CCR5 was active as a coreceptor for M tropic, T tropic, and dual-tropic env proteins. (pnas.org)
  • Formyl-peptide receptors 1, 2 and 3 (FPR1, FPR2 and FPR3) form a subgroup of receptors linked to inhibitory G-proteins (G i ). (mdpi.com)
  • CXCR4, like other G proteins coupled receptors (GPCRs), indicators via heterotrimeric guanine nucleotide joining protein (G protein) to regulate gene transcription, migration, advancement, transformation and growth. (az628.com)
  • Co-receptors are proteins that maintain a three-dimensional structure. (wikipedia.org)
  • CD family receptors are typically monomers or dimers, though they are all primarily extracellular proteins. (wikipedia.org)
  • Recent studies have shown that heteromerization of the chemokine receptors CCR2, CCR5 and CXCR4 is associated to negative binding cooperativity. (nih.gov)
  • In situ hybridization and immunocytochemistry (anti-CXCR4 monoclonal antibody 12G5) revealed both transcript and protein expression in cultured endothelial cells, and in the endothelium of normal aorta but not in aortic smooth muscle. (nih.gov)
  • MDA-MB-231/CXCR4 siRNA knockdown cell line was included as control for antibody specificity. (aacrjournals.org)
  • Blockade of the CXCR4/SDF1 signaling pathway with anti-CXCR4 antibody also decreased transendothelial breast cancer cell migration as well as vascular permeability. (aacrjournals.org)
  • ALX40-4C blocked stromal-derived factor (SDF)-1alpha-mediated activation of CXCR4 and binding of the monoclonal antibody 12G5 to cells expressing CXCR4. (escholarship.org)
  • Receptor chimeras containing the first and second extracellular loops of CXCR4 supported fusion by T tropic and dual-tropic HIV-1 and HIV-2 strains and binding of a monoclonal antibody to CXCR4, 12G5, that blocks CXCR4-dependent infection by some virus strains. (pnas.org)
  • 30 minutes before adoptive transfer of cDCs, WT BALB/c were blocked with 50 mg/mL IV of neutralizing monoclonal antibody (MAb) against CXCR4. (arvojournals.org)
  • Antibiotics were obtained from Gibco-Invitrogen (Carlsbad, CA, USA), and the anti-CXCR4 antibody (rabbit polyclonal) was obtained. (welbourneprimary.com)
  • Current investigations show that chemokine receptor CXCR4 is functionally expressed on a multitude of tissues and cell types, including different leukocyte subsets, hematopoietic progenitor cells and non-hematopoietic cells such as endothelial and epithelial cells. (nih.gov)
  • In 1996 CXCR4 was discovered as one of the co-factors required for supporting T-lymphocyte tropic HIV infection into permissive cells and, as a consequence, much attention has been paid to this receptor in terms of HIV pathophysiology. (nih.gov)
  • These findings provide new insight into the activities of chemokine receptors on both hematopoietic and non-hematopoietic cells and indicate that these molecules have both a more widespread cellular expression pattern and a wider biological role than first envisaged. (nih.gov)
  • The expression of chemokine receptor and viral coreceptor CXCR4 is reported in cultured endothelial cells and in arterial endothelium. (nih.gov)
  • B ] HEK293T cells were transfected with HA-ChemR23 only or with HA-ChemR23 and Flag-ChemR23, CXCR4, CCR7 or Rho-tagged TSHR used as competitors. (nih.gov)
  • Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in different cell types (monocytes, monocyte-derived macrophages, tumor-associated macrophages, endothelial cells, and cancer cells), which is paralleled by increased chemotactic responsiveness to its specific ligand. (rupress.org)
  • They are covalently bound with anti-CXCR4 monoclonal antibodies for immunoreactions with the target sites of the CXCR4 receptors on the CEM-SS cells. (spiedigitallibrary.org)
  • We have studied the role of the constitutive chemokine receptor CXCR4 and its ligand, stromal-derived factor-1 (SDF-1) in the perivascular accumulation of T cells in rheumatoid arthritis. (jimmunol.org)
  • We show that synovial T cells, which are primed CD45RO + CD45RB dull cells and consequently not expected to express constitutive chemokine receptors, have high levels of the chemokine receptor CXCR4. (jimmunol.org)
  • Sustained expression of CXCR4 was maintained on synovial T cells by specific factors present within the synovial microenvironment. (jimmunol.org)
  • Extensive screening revealed that TGF-β isoforms induce the expression of CXCR4 on CD4 T cells in vitro. (jimmunol.org)
  • We found SDF-1 on synovial endothelial cells and showed that SDF-1 was able to induce strong integrin-mediated adhesion of synovial fluid T cells to fibronectin and ICAM-1, confirming that CXCR4 expressed on synovial T cells was functional. (jimmunol.org)
  • These results suggest that the persistent induction of CXCR4 on synovial T cells by TGF-β1 leads to their active, SDF-1-mediated retention in a perivascular distribution within the rheumatoid synovium. (jimmunol.org)
  • The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1-deficient mice and the chemotactic effect of SDF-1 on CD34 + progenitor cells. (bloodjournal.org)
  • Migration of leukemic cells might also depend on the expression of chemokine receptors. (bloodjournal.org)
  • The histograms in the CXCR4 siRNA knockdown panel are isotype control ( open histogram ), MDA-MB-231 cells expressing a negative control siRNA construct ( filled histograms ), and MDA-MB-231 cells expressing CXCR4 siRNA ( open histogram, bold line ). (aacrjournals.org)
  • B, association of Gα i with CXCR4 or Gβ in MDA-MB-231 ( lanes 2 and 3 ) and MDA-MB-453 cells ( lane 4 and 5 ). (aacrjournals.org)
  • 2007). In order to better understand the molecular mechanisms of the biological effects of CXCR4/SDF-1α in thyroid carcer, we performed a global genome expression profile, through DNA microarrays, of CXCR4-expressing human papillary thyroid carcinoma cells (TPC-1) treated or not with SDF-1α. (unina.it)
  • 2008). We found that TPC-1 cells, derived from a human PTC, constitutively express TYRO3 and AXL receptors, but SDF-1α stimulation increased their protein level and tyrosine phosphorylation. (unina.it)
  • The number of CXCR4 immunoreactive cells was expressed as a percentage of the total number of cells. (medsci.org)
  • Both nucleus pulposus cells and cartilaginous endplate cells expressed the CXCR4 protein. (medsci.org)
  • Furthermore, a positive correlation was observed between the SDF-1 IOD value and the percentage of CXCR4-positive disc cells in the nucleus pulposus and cartilaginous endplate. (medsci.org)
  • CXCR4 is constitutively expressed in a wide variety of tissues and cell types, including various subtypes of leukocytes, hematopoietic progenitor cells, and nonhematopoietic cells, such as endothelial and epithelial cells ( 2 ). (aacrjournals.org)
  • CXCR4 is also one of the principal coreceptors for CD4-mediated HIV infection of T cells ( 6 ). (aacrjournals.org)
  • Jurkat cells have high endogenous levels of CXCR4. (aacrjournals.org)
  • Furthermore, T-tropic HIV-1 uses CXCR4 as a co-receptor for viral entry into host cells ( 11 ). (pubmedcentralcanada.ca)
  • Immunoreactive CXCR4 was found mainly in pancreatic cancer cells and endothelial cells of relatively large vessels around a tumorous lesion. (aacrjournals.org)
  • have reported that SDF-1 signaling through CXCR4 interaction appears to determine the directional migration of breast cancer cells through the basement membrane. (knowcancer.com)
  • Furthermore in vivo, the interaction between SDF-1 and CXCR4 significantly represses the metastatic potential of breast cancer cells to lymph node and lung. (knowcancer.com)
  • These results demonstrate that one mechanism by which US27 can enhance CXCR4 signaling is to alter receptor internalization dynamics, which could ultimately have the effect of promoting virus dissemination by increasing trafficking of HCMV-infected cells to tissues where CXCL12 is highly expressed. (physiciansweekly.com)
  • CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. (uni-wuerzburg.de)
  • Unexpectedly, we identified that DLS also has the ability to block CXCL12 binding and activity through CXCR4 on T cells and peripheral blood mononuclear cells (PBMCs). (ijbs.com)
  • Moreover, as CXCR4 has been shown to act as a major co-receptor for HIV-1 entry into CD4 positive host cells, we have also found that DLS partially blocks CXCR4-mediated HIV-1 entry and propagation in activated human PBMCs. (ijbs.com)
  • The CXC chemokine, CXCL12, also known as SDF-1α, is highly expressed in bone marrow stromal cells and potently stimulates the migration of T cells and monocytes via interactions with its cell surface receptor, CXCR4 receptor [ 3 ]. (ijbs.com)
  • CXCR4 is widely expressed on hematopoietic stem cells, cells of the central nervous system, monocytes and T and B lymphocytes [ 4 ]. (ijbs.com)
  • While all the HIV-1 strains require CD4 to enter and infect cells, several laboratory and clinical HIV-1 variants utilize the chemokine receptors CXCR4 (for T-tropic/X4 strain or syncytium-inducing viruses), CCR5 (for M-tropic/R5 strain or non-syncytium-inducing viruses) and/or both receptors (for dual tropic R5X4 strains) for binding and entry. (ijbs.com)
  • The chemokine receptor CXCR4 is a G protein-coupled receptor that plays an important role in several biological processes, such as trafficking and homeostasis of immune cells (like T lymphocytes), alteration of cell skeleton rearrangement and cell migration. (semanticscholar.org)
  • Involvement of the Chemokine Receptor CXCR4 and Its Ligand Stromal Cell-Derived Factor 1α in Breast Cancer Cell Migration Through Human Brain Microvascular Endothelial Cells 1 1NIH grant NS39558 (S. Avraham), the Susan G. Komen Fellowship (S. Avraham), the Milheim Foundation (S. Avraham), CA97153 (H. Avraham), and K18 PAR-02-069 (H. Avraham). (aacrjournals.org)
  • Expression of SDF-1α, the ligand of CXCR4, was about 2-fold higher in microdissected human breast epithelial cancer cells as compared with normal epithelial cells. (aacrjournals.org)
  • Expression of CXCR4 was observed in T lymphocytes, monocytes, and neutrophils ( 11 ), which mediates the chemotactic response to SDF1 by these cells. (aacrjournals.org)
  • Expression of CXCR4 was also found in human neurons, cultured rodent neurons, glial cells ( 17 , 18 ), microglial cells ( 19 ), and endothelial cells ( 20 , 21 ). (aacrjournals.org)
  • Human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins interact with CD4 and chemokine receptors on T cells to deliver signals that trigger either activation, anergy, or apoptosis. (cnrs.fr)
  • Cells expressing a mutant form of CXCR4 with a C-terminal deletion were also sensitive to HIV-1 envelope-mediated apoptosis, indicating that the cytoplasmic tail of CXCR4 is not required to induce the apoptotic pathway. (cnrs.fr)
  • Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressed CXCR4 alone. (escholarship.org)
  • CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. (pasteur.fr)
  • The stem cells with tumor tropic potential are selected based on the stem cells exhibiting CXCR4 receptors or an affinity for the chemokine SDF-1. (freepatentsonline.com)
  • Furthermore, the inhibition of cell-cell fusion in cells expressing CXCR4/CXCR2 chimeric receptors suggested that determinants for sensitivity of CXCR4 to T22 include the three extracellular loops of the coreceptor. (mendeley.com)
  • The chemokine receptors CXCR4 and CCR5 function as coreceptors for HIV-1 entry into CD4 + cells. (pnas.org)
  • CXCR4 expression was rapidly up-regulated on peripheral blood mononuclear cells during phytohemagglutinin stimulation and interleukin 2 priming, and responsiveness to SDF-1 increased simultaneously. (pnas.org)
  • Furthermore, the largely reciprocal expression of CXCR4 and CCR5 among peripheral blood T cells implies distinct susceptibility of T cell subsets to viral entry by T cell line-tropic versus macrophage-tropic strains during the course of HIV infection. (pnas.org)
  • The importance of chemokine receptors in HIV-1 pathogenesis is underscored by the observation that individuals deficient in CCR5 and peripheral blood mononuclear cells (PBMC) from these individuals are resistant to infection by HIV-1 ( 19 , 21 - 24 ). (pnas.org)
  • This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dendritic and T cells during inflammatory and immunological responses. (wikipedia.org)
  • 1997). "Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells" . (wikipedia.org)
  • 1997). "CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells" . (wikipedia.org)
  • CXCR4-mediated HIV entrance was abrogated at sub-micromolar concentrations in HeLa cells (MAGI assay) for any substances except 7 and MSX-122. (thetechnoant.info)
  • Open up in another window Amount 6 Cell surface area CXCR4 expression in a variety of cell typesThe cell surface area CXCR4 appearance was driven via stream cytometry in MDF-7, MDA-MB-231, MDA-MB-468, MDA-MB-468 (knock-in CXCR4) breasts cancer tumor cells, non-tumorigenic MCF-10A cells, HUVEC principal endothelial cells, THP-1 monocytes and Jurkat lymphocytes. (thetechnoant.info)
  • CXCR4 receptor silencing led to decreased ability to signal, to induce migration and to form holoclone-like colonies, with no influence on viability/proliferation of the cells. (edu.pl)
  • CXCR4-deficient cells had also significantly lower levels of MMP-9. (edu.pl)
  • Tumors generated by CXCR4-deficient cells had also lower expression of the proliferation marker Ki‑67 and decreased ability to engraft into lungs and spleen. (edu.pl)
  • In our study CXCR4 influenced invasive properties of cervical carcinoma cells both in vitro and in vivo. (edu.pl)
  • The CXCR4 gene provides instructions for making a receptor protein that spans the outer membrane of cells, specifically white blood cells and cells in the brain and spinal cord (central nervous system). (medlineplus.gov)
  • The CXCR4 receptor is also involved in the movement (migration) of cells. (medlineplus.gov)
  • Cells that have the CXCR4 protein in their membrane are attracted to SDF-1. (medlineplus.gov)
  • Researchers suggest that white blood cells that have the CXCR4 protein in their membrane longer than usual are abnormally retained in the bone marrow (a condition known as myelokathexis). (medlineplus.gov)
  • CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88(L265P) -directed survival signalling in Waldenström macroglobulinaemia cells. (medlineplus.gov)
  • Multiple complementary experimental strategies, including synthetic biology approaches, indicated that signaling-selective inhibition of the CXCR4-Gα 13 -Rho axis prevents the metastatic spread of basal-like breast cancer cells. (sciencemag.org)
  • This receptor is one of several chemokine receptors that HIV isolates can use to infect CD4+ T cells . (thefullwiki.org)
  • Because the interaction between SDF-1 and CXCR4 plays an important role in holding hematopoietic stem cells in the bone marrow, drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. (thefullwiki.org)
  • Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. (physiology.org)
  • The Chemokine Receptor CXCR4 Mediates Recruitment of CD11c+ Dendritic Cells into the Inflammed Murine Corneas. (arvojournals.org)
  • In contrast, CXCR4 was expressed in spermatogonial and meiotic germ cells of normal testis and in the majority of tumour cells. (edu.au)
  • Quantitative RT-PCR identified elevated CXCR4 transcript levels in seminoma compared with normal testis and to non-seminoma, potentially reflecting the higher proportion of dysfunctional germ cells within seminomas. (edu.au)
  • The chemokine receptor CXCR4 is essential for migration and homing of hematopoietic stem cells. (ahajournals.org)
  • 14-16 The CXCR4 receptor, which is highly expressed on both endothelial and hematopoietic progenitor cells, 17,18 has been shown to be essentially involved in mobilization and homing of hematopoietic stem cells, 19,20 and CXCR4-dependent migration toward stromal cell-derived factor-1 (SDF-1) correlated with stem cell function. (ahajournals.org)
  • Given the close relation between hematopoietic progenitor cells and EPC, we investigated the role of CXCR4 and its downstream signaling cascade for the neovascularization capacity of cultured human EPC as well as progenitor cells derived from mice. (ahajournals.org)
  • Recent evidence shows that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with 1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) which CXCR4:1A/B-AR heteromers are essential for 1-AR function in vascular easy muscle cells (VSMC). (labourlists.org)
  • Targeting the CXCR4-CXCL12 axis thus offers the possibility of affecting CXCR4-expressing primary tumor cells, modulating the immune response, or synergizing with other targeted anticancer therapies. (aacrjournals.org)
  • Encoded on chromosome 2q21, CXCR4 is an evolutionarily highly conserved GPCR expressed on monocytes, B cells, and naïve T cells in the peripheral blood. (aacrjournals.org)
  • Recent studies have shown CXCR4 signaling through mTOR in pancreatic cancer, gastric cancer, and T-cell leukemia cells ( 10-13 ). (aacrjournals.org)
  • This is the peer-reviewed but unedited manuscript version of the following article: Cunha F, Rajnicek A, M, McCaig C, D: Electrical Stimulation Directs Migration, Enhances and Orients Cell Division and Upregulates the Chemokine Receptors CXCR4 and CXCR2 in Endothelial Cells. (abdn.ac.uk)
  • CXCR4 and vascular cell adhesion molecule 1 are key chemokine/adhesion receptors in the migration of cytokine-activated T cells. (ox.ac.uk)
  • RESULTS: Cytokine stimulation up-regulated the expression of chemokine receptors and integrins on Tck cells, including CXCR4, very late activation antigen 4 (VLA-4), and lymphocyte function-associated antigen 1. (ox.ac.uk)
  • CXCR4, the stromal cell-derived aspect-1 receptor, takes on an important part in the migration of hematopoietic progenitor/come cells to injured and inflamed areas. (welbourneprimary.com)
  • CXCR4, the stromal cell-derived element-1 (SDF) receptor, takes on an essential part in the migration of hematopoietic progenitor/come cells [25]. (welbourneprimary.com)
  • The overexpression of CXCR4 in human being hematopoietic come cells or Compact disc34+ progenitors offers been demonstrated to improve chemotaxis, migration, and homing [26]. (welbourneprimary.com)
  • Nevertheless, there are limited non-invasive research displaying the migration strength of these restorative CXCR4-overexpressing cells to tumor cells in Geldanamycin pet versions. (welbourneprimary.com)
  • CXCR4 localizes to both early and recycling where possible endosomes in Compact disc34+ cells (19), and CXCR4 recycling where possible requires cortactin in HEK293 cells (11) and PIM1 in Capital t cells (20). (az628.com)
  • The purpose of this study was to explore the expression characteristics of SDF-1 receptor, CXCR4 , in mesenchymal stem cells (MSC) of different passages derived from human umbilical cord (hucMSC). (bvsalud.org)
  • However, the effects of simultaneous genome editing of CXCR4 and CCR5 by CRISPR-Cas9 in blocking HIV-1 infection in primary CD4 + T cells has been rarely reported. (biomedcentral.com)
  • The CRISPR-sgRNAs-Cas9 could successfully induce editing of CXCR4 and CCR5 genes in various cell lines and primary CD4 + T cells. (biomedcentral.com)
  • Using HIV-1 challenge assays, we demonstrated that CXCR4-tropic or CCR5-tropic HIV-1 infections were significantly reduced in CXCR4 - and CCR5 -modified cells, and the modified cells exhibited a selective advantage over unmodified cells during HIV-1 infection. (biomedcentral.com)
  • In addition, apoptosis assays indicated that simultaneous disruption of CXCR4 and CCR5 in primary CD4 + T cells by CRISPR-Cas9 had no obvious cytotoxic effects on cell viability. (biomedcentral.com)
  • HIV-1 infection of CD4 + T cells involves binding of the viral protein gp120 to the primary cellular receptor CD4 and either of the co-receptors, CCR5 or CXCR4. (biomedcentral.com)
  • MEDI3185 variations had been expressed in Chinese language hamster ovary (CHO) cells and their binding to human being CXCR4 evaluated using circulation cytometry (Fig.?2). (gasyblog.com)
  • All mutants indicated well on the top of CHO cells (Fig.?3B) while monitored using mAb 2B11, which recognizes CXCR4?N-terminal peptide.57 MEDI3185 binding to these CXCR4 variants was assessed by flow cytometry. (gasyblog.com)
  • Furthermore, we establish that the capacity to use the chemokine receptor CXCR4 for entry determines whether a virus will enter multipotent versus differentiated progenitor cells. (elsevier.com)
  • PMP can transfer some adhesion molecules such as CXCR4 to CXCR4-negative cells. (ac.ir)
  • CXCR4-negative cell lines (1×105 cells/ml) were cultured in RPMI1640 with 10% FBS and 1% antibiotic. (ac.ir)
  • The presence of CXCR4 on cells was analyzed by flowcytometry. (ac.ir)
  • PMPs in different concentrations can transfer CXCR4 to target cells. (ac.ir)
  • Also, the increase of PMPs concentration up to 250µg/mL can increase the CXCR4 presence on null cells. (ac.ir)
  • Enhancing cell surface expression of cytokine receptor CXCR4 to promote neural stem cell migration towards brain tumor (glioma) cells. (csuci.edu)
  • It has been also shown that CXCR4 signalling regulates the expression of CD20 on B cells. (wikipedia.org)
  • Drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. (wikipedia.org)
  • In a small human clinical trial to evaluate the safety and efficacy of fucoidan ingestion (brown seaweed extract), 3g daily of 75% w/w oral fucoidan for 12 days increased the proportion of CD34+CXCR4+ from 45 to 90% and the serum SDF-1 levels, which could be useful in CD34+ cells homing/mobilization via SDF-1/CXCR4 axis. (wikipedia.org)
  • Co-receptors localized in endothelial cells function to enhance cell proliferation and cell migration. (wikipedia.org)
  • The CD family of co-receptors are a well-studied group of extracellular receptors found in immunological cells. (wikipedia.org)
  • These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12 and with the HIV-1 glycoprotein gp120. (pubmedcentralcanada.ca)
  • Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. (escholarship.org)
  • T22 bound to CXCR4 and interfered with stromal-cell-derived factor-1alpha-CXCR4 interactions in a competitive manner. (mendeley.com)
  • These acidic residues could engage electrostatical interactions with basic residues of the HIV-1 envelope protein gp120, known to contribute to the selectivity for CXCR4. (pasteur.fr)
  • 1998). "Structural interactions between chemokine receptors, gp120 Env and CD4. (thefullwiki.org)
  • Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that exhibits chemokine-like activities through non-cognate interactions with the chemokine receptors CXCR2 and CXCR4, in addition to activating the type II receptor CD74. (jpt.com)
  • This project focuses on investigating clinically acceptable techniques to increase the efficiency of NSC-GBM interactions by upregulating CXCR4 surface protein expression. (csuci.edu)
  • Following chemical SYK inhibition, all BCR-dependent DLBCLs exhibited significantly increased stromal cell-derived factor-1α (SDF-1α) induced chemotaxis, consistent with the role of CXCR4 signaling in B-cell migration. (haematologica.org)
  • A mAb to CXCR4, 12G5, showed partial inhibition of chemotaxis and calcium influx induced by SDF-1, the natural ligand of CXCR4. (pnas.org)
  • Using a genetic strain of Saccharomyces cerevisiae that expresses a functional CXCR4 receptor, site-specific mutagenesis, hybrid CXCR3/CXCR4 receptors, pharmacological reagents, peptide array analysis, chemotaxis, fluorescence spectroscopy, and circular dichroism, we provide novel molecular information about the structural elements that govern the interaction between MIF and CXCR4. (jpt.com)
  • To measure the ramifications of the TM peptide analogs on CXCR4-mediated results, we first assessed CXCL12-induced chemotaxis as an operating read-out. (labourlists.org)
  • The third intracellular loop of CXCR4 is necessary for Gαi-dependent signaling, and intracellular loops 2 and 3 as well as the C-terminus of CXCR4 are required for chemotaxis ( 6, 7 ). (aacrjournals.org)
  • Dysregulation of the chemokine receptor CXCR4 is relevant in melanoma progression, and the CXCR4/CXCL12 axis has been shown to activate cell cycle progression and malignant cell migration through stimulation of the mitogen-activated protein kinase pathway. (biomedsearch.com)
  • Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation and development. (pubmedcentralcanada.ca)
  • Our results suggested that the SDF-1/CXCR4 receptor ligand system may have a possible role in the pancreatic cancer progression through tumor cell migration and angiogenesis. (aacrjournals.org)
  • Our findings also suggest that structural analogues that mimic DLS binding properties may also have properties of blocking HIV infectivity, CXCR4 dependent cancer cell migration and attenuating chemokine-mediated immune cell trafficking in inflammatory disorders. (ijbs.com)
  • Thus, the expression of chemokine receptors and their regulation is thought to influence lymphocyte migration, as well as HIV infection and AIDS pathogenesis. (pnas.org)
  • Incubation of EPC from healthy volunteers with neutralizing antibodies against CXCR4 profoundly inhibited vascular endothelial growth factor- and stromal-derived factor-1-induced migration as well as EPC-induced angiogenesis in an ex vivo assay. (ahajournals.org)
  • CXCL12 exists in a monomer-dimer equilibrium in which both states bind CXCR4 and stimulate a calcium response, but only the monomeric variant promotes cell migration ( 7, 8 ). (aacrjournals.org)
  • CXCR4 indicators to regulate Capital t cell advancement (1), migration (2), cytokine gene release and phrase, and co-stimulates Capital t lymphocyte immune system service (2-5). (az628.com)
  • Although the jobs of Rho GTPases in mediating post-endocytic CXCR4 trafficking possess not really been characterized, CXCR4 activates Rho in response to SDF-1 treatment, and this can be needed for migration (23, 24). (az628.com)
  • Cholesterol-modified PCX showed maximum CXCR4 antagonism, NCOA3 silencing and inhibition of PC cell migration in vitro. (elsevier.com)
  • The migration of the primordium is driven by the chemokine SDF1 and by its receptor CXCR4, encoded respectively by the genes sdf1a and cxcr4b . (biomedcentral.com)
  • We propose that directionality is imposed on the primordium as soon as it comes in contact with the stripe of SDF1, and is maintained throughout migration by a negative interaction between the two receptors. (biomedcentral.com)
  • This has led to substantial progress in understanding the cell biology of migration as well as the many receptor molecules and signaling cascades involved. (biomedcentral.com)
  • Co-receptors have been identified as participants in cell signalling cascades, embryonic development, cell adhesion regulation, gradient formation, tissue proliferation and migration. (wikipedia.org)
  • To initiate a HIV infection, the viral envelope glycoprotein gp120 comes in contact with a cellular receptor of T-lymphocyte known as CD4, followed by interaction with co-receptors, e.g. (spiedigitallibrary.org)
  • 5 , 6 , 7 Therefore, it is imperative to be able to effectively detect the CXCR4 receptors on the T-cell surface that can serve as an important tool in understanding the molecular mechanism of HIV infection, especially when CXCR4 interacts with its ligand and/or with viral gp120. (spiedigitallibrary.org)
  • Monoclonal antibodies directed against the gp120-binding site on CD4 (ST4) and against CXCR4 (MAB173) prevented the apoptotic signal in a dose-dependent manner. (cnrs.fr)
  • The cell death program was also inhibited by SDF-1 alpha, the natural ligand of CXCR4, and by suramin, a G protein inhibitor that binds with a high affinity to the V3 loop of HIV-1 gp120 envelope protein. (cnrs.fr)
  • These results highlight the role played by gp120-binding on CXCR4 to trigger programmed cell death. (cnrs.fr)
  • HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages. (thefullwiki.org)
  • 2004). "Chemokine receptor utilization and macrophage signaling by human immunodeficiency virus type 1 gp120: Implications for neuropathogenesis. (thefullwiki.org)
  • Bath application of stromal cell-derived factor-1α (SDF-1α), the only CXCR4 ligand, mimicked the effects of gp120 on GDPs, supporting the engagement of CXCR4 receptors in the gp120-induced increase of GDP occurrence. (nebraska.edu)
  • As well as being involved in forming a complex with MHC-II with TCR to control T-cell fate, the CD4 receptor is infamously the primary receptor that HIV envelope glycoprotein GP120 binds to. (wikipedia.org)
  • In a relay multistep navigation process, the Hyp-Hyp-inducible factor 1 α-CXCR4 pathway may regulate trafficking in and out of hypoxic tissue microenvironments. (rupress.org)
  • Although chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 induce degradation of articular cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA), the association between the SDF-1/CXCR4 pathway and degradation of the cartilaginous endplate and nucleus pulposus has not been thoroughly clarified. (medsci.org)
  • These findings implicate the SDF-1/CXCR4 axis in a variety of cancers, which may make this pathway an interesting target for the development of drugs against cancer and HIV. (aacrjournals.org)
  • B-cell receptor (BCR) signaling pathway components represent promising treatment targets in multiple B-cell malignancies including diffuse large B-cell lymphoma (DLBCL). (haematologica.org)
  • Altogether, our results demonstrate that HIV induces a caspase-dependent apoptotic signaling pathway through CXCR4. (cnrs.fr)
  • 4 The chemotactic effect of SDF-1 is mediated by the chemokine receptor CXCR-4 (fusin, LESTR), which is expressed on mononuclear leukocytes and shows structural similarities to the IL-8 receptor. (bloodjournal.org)
  • This protein, termed fusin, was designated CXCR4 when it was shown to bind the CXC chemokine SDF-1 ( 11 , 12 ). (pnas.org)
  • CXCR4 , (a CXC chemokine R eceptor ), also called fusin , is an alpha- chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes . (thefullwiki.org)
  • C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene. (wikipedia.org)
  • A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. (escholarship.org)
  • Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion. (escholarship.org)
  • ref. 11 ), which may render wtCXCL12 a poor choice as a therapeutic inhibitor of CXCR4. (aacrjournals.org)
  • G protein-coupled receptors (GPCRs) are biological switches that transduce extracellular stimuli into intracellular responses in the cell. (mdc-berlin.de)
  • The location and shape of the ligand binding sites differ from other G protein-coupled receptors and are closer to the extracellular surface. (pubmedcentralcanada.ca)
  • Blocking of anti-CXCR4 monoclonal antibodies by T22 suggested that the peptide interacts with the N terminus and two of the extracellular loops of CXCR4. (mendeley.com)
  • Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation. (proteopedia.org)
  • The second extracellular loop of CXCR4 was sufficient to confer coreceptor function to CXCR2 for most virus strains tested but did not support binding of 12G5. (pnas.org)
  • We propose that dual tropism may evolve in CCR5-restricted HIV-1 strains through acquisition of the ability to utilize the first and second extracellular loops of CXCR4 while retaining the ability to interact with the CCR5 amino-terminal domain. (pnas.org)
  • The large extracellular domains make up approximately 76-100% of the receptor. (wikipedia.org)
  • Interaction with CXCR4 was completely abolished for CXCL12-3Cit and CXCL12-5Cit. (jimmunol.org)
  • The ability of CXCR4 mutants to bind SDF-1 and mediate cell signal was consistent with the two-site model of chemokine-receptor interaction. (pasteur.fr)
  • Additionally, troxerutin inhibited the increased protein level of stromal-derived factor-1(SDF-1), C-X-C chemokine ligand 12 receptor 4 (CXCR4), and thioredoxin interaction protein (TXNIP) caused by BDE-47. (hindawi.com)
  • Specifically, the immunoprecipitation assay indicated that there was a direct interaction between CXCR4 and TXNIP. (hindawi.com)
  • The interaction between CXCR4 and CXCL12 exhibits a highly potent chemoattraction in vivo ( 26 , 30 , 36 , 41 ). (physiology.org)
  • Although the structural basis of the MIF-CXCR2 interaction has been well studied and was found to engage a pseudo-ELR and an N-like loop motif, nothing is known about the regions of CXCR4 and MIF that are involved in binding to each other. (jpt.com)
  • The involvement of CXCR4 in chemokine signaling, chemoattraction (through SDF-1), and its potential viral coreceptor activity suggest a multifunctional role in vascular homeostasis and pathophysiology. (nih.gov)
  • The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell- tropic human immunodeficiency virus (HIV)-1 strains, whereas CCR5 is used by macrophage (M)-tropic strains. (escholarship.org)
  • ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T- and dual-tropic HIV-1 strains, whereas use of CCR5 by M- and dual-tropic strains was not inhibited. (escholarship.org)
  • CXCR4 is a G-coupled receptor for the stromal cell-derived factor (SDF-1) chemokine, and a CD4-associated human immunodeficiency virus type 1 (HIV-1) coreceptor. (pasteur.fr)
  • The coreceptor activity of CXCR4 was markedly impaired by mutations of two Tyr residues in NT (Y7A/Y12A) or at a single Asp residue in ECL2 (D193A), ECL3 (D262A), or TMII (D97N). (pasteur.fr)
  • The chemokine receptor CXCR4 functions as a fusion coreceptor for T cell tropic and dual-tropic HIV-1 strains. (pnas.org)
  • To identify regions of CXCR4 that are important for coreceptor function, CXCR4-CXCR2 receptor chimeras were tested for the ability to support HIV-1 envelope (env) protein-mediated membrane fusion. (pnas.org)
  • Truncation of the CXCR4 cytoplasmic tail or mutation of a conserved DRY motif in the second intracellular loop did not affect coreceptor function, indicating that phosphorylation of the cytoplasmic tail and the DRY motif are not required for coreceptor function. (pnas.org)
  • Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. (abcam.com)
  • In comparison, CD28 acts as a 'co-coreceptor' (costimulatory receptor) for the MHC-II binding with TCR and CD4. (wikipedia.org)
  • Activation of the MIF-CXCR2 and -CXCR4 axes promotes leukocyte recruitment, mediating the exacerbating role of MIF in atherosclerosis and contributing to the wealth of other MIF biological activities. (jpt.com)
  • Despite a wealth of data related to CXCR4 and GPCRs in general, many aspects of ligand binding and signaling are poorly understood at the molecular level. (pubmedcentralcanada.ca)
  • One of these is the US27 gene, which encodes a protein with homology to the chemokine receptor family of G protein-coupled receptors (GPCRs). (physiciansweekly.com)
  • The CCR family of receptors are a group of g-protein coupled receptors (GPCRs) that normally operate as chemokine receptors. (wikipedia.org)
  • Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4. (wikipedia.org)
  • Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries ( p= 0.01) and local recurrences ( p= 0.04). (frontiersin.org)
  • First, cell surface receptors can directly transduce signals by possessing both serine and threonine or simply serine in the cytoplasmic domain. (wikipedia.org)
  • Secondly, certain surface receptors lacking a cytoplasmic domain can transduce signals through ligand binding. (wikipedia.org)
  • Most co-receptors lack a cytoplasmic domain and tend to be GPI-anchored, though a few receptors have been identified which contain short cytoplasmic domains that lack intrinsic kinase activity. (wikipedia.org)
  • The C-X-C chemokine receptor-4(CXCR4) is a G-protein coupled receptor (GPCR) which belongs to the family I GPCR or rhodopin-like GPCR family. (eurekaselect.com)
  • Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation. (semanticscholar.org)
  • CXCR4 has several biochemical functions, for example, C-X-C chemokine receptor activity, G-protein coupled receptor activity, actin binding. (creativebiomart.net)
  • The protein encoded by this gene is a member of the G-protein-coupled receptor family. (wikipedia.org)
  • This protein belongs to family A of G protein-coupled receptor superfamily. (wikipedia.org)
  • An activated G protein-coupled receptor (human β-2 adrenergic receptor in blue ) in a complex with a heterotrimeric G protein (3 subunits:reddish to orange-brown) and hormone (gold) ( 3sn6 ), resolution 3.2Å. (proteopedia.org)
  • Belongs to the G-protein coupled receptor 1 family. (abcam.com)
  • As well as being important for lymphocyte trafficking and recruitment at sites of inflammation, it appears that CXCR4 and its ligand stromal cell-derived factor-1 play an important role in hematopoiesis and developmental processes such as organogenesis, vascularization and embryogenesis. (nih.gov)
  • The ligand for CXCR4, stromal cell derived factor 1 (SDF-1) stimulated mobilization of intracellular calcium at a moderate level (37% of the peak response to thrombin), confirming the expression of functional receptor at the endothelial surface. (nih.gov)
  • Zhang H, Zhang L, Chen L, Li W, Li F, Chen Q. Stromal Cell-derived Factor-1 and its Receptor CXCR4 are Upregulated Expression in Degenerated Intervertebral Discs. (medsci.org)
  • The chemokine receptor CXCR4 and its ligand, stromal cell-derived factor-1 (SDF-1), play important roles in hematopoiesis regulation, lymphocyte activation, and trafficking, as well as in developmental processes, including organogenesis, vascularization, and embryogenesis. (aacrjournals.org)
  • Stromal cell-derived factor 1α (SDF-1α) is a member of the CXC or α-chemokine subfamily and is the only known ligand for the chemokine receptor CXCR4 ( 7 -9 ). (aacrjournals.org)
  • This gene encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. (creativebiomart.net)
  • Although most chemokine receptors bind more than one ligand ( 3 ), CXCR4 is a unique receptor for stromal cell-derived factor 1α (SDF-1α)/CXCL12, which is constitutively expressed in lymph nodes, lung, liver, and bone marrow ( 26 , 30 , 36 , 41 ). (physiology.org)
  • However, basal Janus kinase (JAK)-2 phosphorylation was significantly reduced and less responsive to stromal-derived factor-1 in EPC from patients with CAD compared with healthy volunteers, indicating that CXCR4-mediated JAK-2 signaling is dysregulated in EPC from patients with CAD. (ahajournals.org)
  • The chemokine stromal-derived factor (SDF)-1 and its unique receptor CXCR4 are essential for normal cardiovascular development but also play a critical role in postnatal vasculogenesis. (ahajournals.org)
  • CXCR4 is the receptor for the stromal cell-derived factor-1 (SDF-1)/CXCL12 chemokine and it is expressed in a variety of solid tumors, including papillary thyroid carcinoma. (unina.it)
  • Using a metal nanoshell as molecular imaging agent, we develop a cellular model system to detect CXCR4 chemokine receptor on T-lymphatic cell surface. (spiedigitallibrary.org)
  • Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. (frontiersin.org)
  • Here, we report highly significant transcriptional upregulation of C-X-C chemokine receptor 4 (CXCR4) in BCR-dependent DLBCL cell lines and primary tumors following chemical spleen tyrosine kinase (SYK) inhibition, molecular SYK depletion or chemical PI3K blockade. (haematologica.org)
  • Somatostatin receptors (SSTR) are known for their overexpression in well-differentiated GEP-NEN, where they serve as molecular targets for different imaging and treatment modalities. (enets.org)
  • Concomitant overexpression of EGFR and CXCR4 is associated with worse prognosis in a new molecular subtype of non-small cell lung cancer. (semanticscholar.org)
  • This way, this Research Topic summarizes latest knowledge on this crucial molecular axis and its relationship with cardiovascular pathologies for both specialists and interested non-specialists and aims to stimulate further initiatives to unravel the mechanistic involvement of the CXCR4 ligand/receptor family in these morbidities, potentially paving the way for new therapeutical initiatives in the future. (doabooks.org)
  • BACKGROUND: Biological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II (topo II), P-glycoprotein (P-gp) and glutathione S-transferase (GST) were observed for changes after administration of neochemotherapy and whether these protein expression changes were correlated with response to chemotherapy. (biomedsearch.com)
  • Background The chemokine receptor 4 (CXCR4) can be an important molecular target for both visualization and therapy of tumors. (biosweepny.com)
  • Understanding the molecular systems that CXCR4 uses to control its endocytic trafficking and cell-surface amounts can be consequently important to understanding the physical and disease features of CXCR4. (az628.com)
  • Very much much less can be realized about the molecular signaling systems accountable for controlling CXCR4 trafficking into non-lysosomal spaces including recycling where possible endosomes. (az628.com)
  • B, evaluation of CXCR4 cell surface expression by flow cytometry. (aacrjournals.org)
  • 6 h of treatment sufficient to augment CXCR4 on T lymphocytes. (physiology.org)
  • Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise. (physiology.org)
  • Among various chemokine receptors, C-X-C motif chemokine receptor 4 (CXCR4) on CD4 T lymphocytes can be augmented by a synthetic glucocorticoid, dexamethasone ( 40 ). (physiology.org)
  • Chronic exposure to THC has been shown to increase T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes in rhesus macaques. (wikipedia.org)
  • In most cell lines, the two receptors display high levels of tyrosine-phosphorylation, due to constitutive expression of GAS6. (unina.it)
  • Replacement of only Arg 8 caused already impaired (30-fold reduction) CXCR4 binding and signaling (calcium mobilization, phosphorylation of ERK and protein kinase B) properties. (jimmunol.org)
  • Disturbance of CXCR4 signaling, as demonstrated by reduced JAK-2 phosphorylation, may contribute to functional impairment of EPC from patients with CAD. (ahajournals.org)
  • CXCR4 internalization needs phosphorylation of the CXCR4 carboxyl-terminal end site, which provokes endocytosis via -arrestin (6, 8). (az628.com)
  • Effect of human cytomegalovirus (HCMV) US27 on CXCR4 receptor internalization measured by fluorogen-activating protein (FAP) biosensors. (physiciansweekly.com)
  • FAP-tagged CXCR4 and US27 were used to explore receptor internalization and recovery dynamics, and the results demonstrate that significantly more CXCR4 internalization was observed in the presence of US27 compared to CXCR4 alone upon stimulation with CXCL12. (physiciansweekly.com)
  • While ligand-induced endocytosis rates were higher, steady state internalization of CXCR4 was not affected by US27. (physiciansweekly.com)
  • Leukocytes from individuals with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency, and bearing a wild-type CXCR4 ORF (WHIM WT ) display impaired CXCR4 internalization and desensitization upon exposure to CXCL12. (jci.org)
  • As in Waldenström macroglobulinemia, the CXCR4 gene mutations that cause WHIM syndrome impair internalization of the CXCR4 protein. (medlineplus.gov)
  • To handle the chance that the noticed adjustments in PLA indicators are due to TM peptide analog-induced receptor internalization, we after that studied receptor manifestation amounts on hVSMC by FACS analyses. (labourlists.org)
  • In some cell types, CXCR4 internalization also is dependent on Hip (9), myosin IIA (10), cortactin (11), Rab5 (12, Mefloquine HCl 13), and/or the dileucine theme within the carboxyl-terminal end site of CXCR4 (14). (az628.com)
  • Because HSCs live for the life span of the infected person and are crucial for hematopoietic health, these data may explain the poor prognosis associated with CXCR4-tropic HIV infection and suggest HSCs as long-lived cellular reservoirs of latent HIV. (elsevier.com)
  • It also inhibits binding of the CXC-chemokine, SDF-1alpha, to CXCR4 and subsequent signal transduction, but does not itself cause signaling and has no effect on RANTES signaling via CCR5. (nih.gov)
  • The term co-receptor is prominent in literature regarding signal transduction, the process by which external stimuli regulate internal cellular functioning. (wikipedia.org)
  • We show, using BRET and HTRF assays, that ChemR23 forms homomers, and provide data suggesting that ChemR23 also forms heteromers with the chemokine receptors CCR7 and CXCR4. (nih.gov)
  • Introduction: There is abundant evidence showing that chemokine CXCL12 and its receptor CXCR4 are involved in glioma progression and angiogenesis. (usp.br)
  • Depletion studies using synovial fluid confirmed an important role for TGF-β1 in the induction of CXCR4 expression in vivo. (jimmunol.org)
  • In this study, we investigated the role of the SDF-1/CXCR4 axis during cervical carcinoma growth and progression in vitro and in vivo. (edu.pl)
  • Interestingly, downregulation of CXCR4 expression resulted in reduced tumor growth in vivo. (edu.pl)
  • The importance of chemokine receptors for virus infection in vivo was shown by the discovery of a CCR5 polymorphism for which approximately 1% of the Caucasian population is homozygous ( 19 , 20 ). (pnas.org)
  • Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. (physiology.org)
  • was CXCR4-particular and greater than in all various other organs and led to high res delineation of Daudi tumors in Family pet/CT pictures in vivo. (biosweepny.com)
  • Conclusions [64Cu]NOTA-pentixather was fast and effectively radiolabeled, demonstrated effective CXCR4-concentrating on, Rabbit Polyclonal to SF3B3 high balance in vitro and in vivo and led to high resolution Family pet/CT images followed with the right biodistribution profile, producing [64Cu]NOTA-pentixather a appealing tracer for potential application in human beings. (biosweepny.com)
  • Ex vivo, differentiated EPC derived from peripheral blood abundantly expressed CXCR4. (ahajournals.org)
  • Although CXCR4 can be indicated by MSCs within the bone tissue marrow [23] extremely, its appearance can be decreased during ex girlfriend or boyfriend vivo development [24] substantially, which lowers their capability to house to wounded sites. (welbourneprimary.com)
  • Therefore, in the current study, we established CXCR4-overexpressing MSCs, containing a reporter gene, and evaluated their in vivo migrating efficiency to triple negative breast cancer by BLI. (welbourneprimary.com)
  • 1 , 2 , 3 , 4 As a key co-receptor, CXCR4 thus takes an important role in the HIV-1 infection. (spiedigitallibrary.org)
  • In fact, CXCR4 is specifically recognized by the R4 virus during the early phases of the HIV-1 infection. (spiedigitallibrary.org)
  • Thus, the discovery that endogenous CXCL12 inhibits HIV-1 entry suggested the therapeutic potential of targeting CXCR4 to block viral infection ( 12 - 13 ). (pubmedcentralcanada.ca)
  • We recently reported that a cationic peptide, T22 ([Tyr(5,12), Lys(7)]-polyphemusin II), specifically inhibits human immunodeficiency virus type 1 (HIV-1) infection mediated by CXCR4 (T. Murakami et al. (mendeley.com)
  • During the early stages of HIV infection, viral isolates tend to use CCR5 for viral entry, while later isolates tend to use CXCR4. (pnas.org)
  • The chemokine receptor CXCR4 plays an intrinsic role in the introduction of highly metastatic breast cancer and in the pathogenesis of chronic HIV infection. (thetechnoant.info)
  • For example, zinc finger nucleases (ZFN), transcription activator like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 have been utilized to successfully disrupt the HIV-1 co-receptors CCR5 or CXCR4, thereby restricting HIV-1 infection. (biomedcentral.com)
  • Our results suggest that simultaneous genome editing of CXCR4 and CCR5 by CRISPR-Cas9 can potentially provide an effective and safe strategy towards a functional cure for HIV-1 infection. (biomedcentral.com)
  • Further studies confirmed that people who lack a functional CCR5 co-receptor, due to the mutation, were resistant to HIV-1 infection [ 17 ]. (biomedcentral.com)
  • The serum concentrations of CXCL12 were significantly higher, while those of its receptor CXCR4 were significantly lower in EC patients compared to healthy controls. (hindawi.com)
  • Recently, crystal structure of human CXCR4 receptor was reported, which facilitates the structure-based drug discovery of CXCR4 significantly. (eurekaselect.com)
  • SDF-1 and CXCR4 were both expressed in IVDs, and the levels of SDF-1 and CXCR4 were both significantly higher in the degeneration group than in the normal group of human (or rat) discs. (medsci.org)
  • Diagnostics and therapy of NET are significantly influenced by their somatostatin receptor (SSTR) status. (enets.org)
  • All patients were divided into either a correlated (significantly higher or lower correlation between CXCL12 and CXCR4 expression) or uncorrelated groups. (cdc.gov)
  • The gene expression of CXCL-12 and CXCR4 was significantly different between gastric cancer tissues and normal gastric tissues. (cdc.gov)
  • concluded that CXCR4 plays an important role of proliferation and tumorigenic properties of human glioblastoma tumors. (knowcancer.com)
  • Somatostatin receptors (SSTR) are widely distributed in well-differentiated neuroendocrine tumors (NET) and serve as primary targets for diagnostics and treatment. (enets.org)
  • Receptor PET/CT with somatostatin analogues marked with Gallium-68 (SMS-R-PET/CT) is currently the golden standard in diagnosing gastroenteropancreatic neuroendocrine tumors (GEP-NET), which are known for an overexpression of somatostatin receptors (SSTRs). (enets.org)
  • Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are known for an overexpression of somatostatin receptors (SSTR). (enets.org)
  • The chemokine receptor CXCR4, in contrast, is present mainly in highly proliferative and advanced tumors. (enets.org)
  • Ga-68 somatostatin receptor (SSTR) PET/CT is one of the most sensitive imaging methods for pancreatic neuroendocrine tumors. (enets.org)
  • DOTA is linked to molecules that have affinity for various structures (e.g. somatostatin receptors in neuroendocrine tumors). (jpt.com)
  • Multiple bad breast tumor (TNBC) is definitely a subtype of tumors that do not clinically communicate human being epidermal growth element receptor 2 (HER-2), progesterone receptor (PR), or estrogen receptor (Emergency room). (welbourneprimary.com)
  • A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. (frontiersin.org)
  • CXCR4 expression in a panel of human breast cancer cell lines. (aacrjournals.org)
  • C, comparison of cell surface expression levels of CXCR4 on human breast cancer cell lines presented as the MFI. (aacrjournals.org)
  • In this thesis project, we provide evidences that targeting CXCR4/SDF-1 or TYRO3/AXL/GAS6 axis might be exploited as novel anticancer therapyes for human thyroid carcinomas. (unina.it)
  • SDF-1 and CXCR4 levels in human IVDs and the rat L5/6 motion segment were quantified by enzyme-linked immunosorbent assay. (medsci.org)
  • 50%) G3 (n=43) neuroendocrine neoplasms by means of immunohistochemistry using novel monoclonal rabbit anti-human anti-SSTR and anti-CXCR4 antibodies and correlated to clinical data. (enets.org)
  • We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). (uni-wuerzburg.de)
  • Interestingly, the chemokine receptors CXCR4 and CCR5 have attracted substantial interest because they form portals of cellular entry for the human immunodeficiency viruses (HIV-1 and HIV-2) and related simian or feline retroviruses[ 5 ]. (ijbs.com)
  • CXCR4 in human osteosarcoma malignant progression. (semanticscholar.org)
  • The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS. (mcw.edu)
  • This receptor is highly conserved between human and rodent. (pasteur.fr)
  • The human β2 adrenergic receptor bound to a G-protein ( 3sn6 ) is featured in a scene on the right, and additional structures are on the Adrenergic receptor page . (proteopedia.org)
  • CXCR4 is upregulated during the implantation window in natural and Hormone Replacement Therapy cycles in the endometrium, producing, in presence of a human blastocyst , a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation . (thefullwiki.org)
  • Therefore, we investigated the role of CXCR4 and its downstream signaling cascade for the angiogenic capacity of cultured human EPC. (ahajournals.org)
  • The CXCR4 receptor signaling profoundly modulates the angiogenic activity and homing capacity of cultured human EPC. (ahajournals.org)
  • Human CXCR4 was originally identified as a receptor for CXCL12 by screening CKR orphan genes for their ability to induce intracellular Ca +2 in response to human CXCL12. (aacrjournals.org)
  • Thus, we suggest that CXCR4 targeting is a novel potential strategy in the treatment of human ATC. (unina.it)
  • SIGNIFICANCE STATEMENT: The CXCL12/CXCR4 axis represents a well-established therapeutic target for cancer treatment. (mdc-berlin.de)
  • Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. (uni-wuerzburg.de)
  • Given the involvement of CXCR4 and CCR5 in HIV, cancers, stem cell mobilization and inflammation, these receptors have emerged as potential targets for therapeutic manipulation and intervention [ 5 ]. (ijbs.com)
  • The success of therapeutic approaches that interfere with the function of HER2/Neu [also known as ErbB2, a member of the epidermal growth factor (EGF) receptor family] or of the estrogen receptor has markedly reduced breast cancer mortality. (sciencemag.org)
  • Antagonistic antibodies targeting the G-protein C-X-C chemokine receptor 4 (CXCR4) keep encouraging therapeutic potential in a variety of diseases. (gasyblog.com)
  • imply CXCR4:1A-AR heteromers are essential for intrinsic 1-AR function in undamaged arteries and offer initial and unpredicted insights in to the rules of CXCR4 Rabbit Polyclonal to CHFR heteromerization in VSMC. (labourlists.org)
  • Emerging evidence shows that the expression and function of G-protein-coupled receptors is strictly controlled by cytokines and other microenvironmental signals, such as Hyp ( 10 - 12 ), and that the regulation of receptor expression during cell activation and deactivation is as important as the regulation of chemokine production for tuning the chemokine system ( 13 ). (rupress.org)
  • The serum concentrations of CXCL12 and CXCR4 and classical tumor markers such as carcinoembryonal antigen (CEA) and squamous cell cancer antigen (SCC-Ag) were measured using immunoenzyme assays, while C-reactive protein (CRP) levels were assessed by immunoturbidimetric method. (hindawi.com)
  • Because there is an average of ~6000 binding sites on the cell surface, we estimate that one emission spot from the metal nanoshell may represent ~30 CXCR5 receptors. (spiedigitallibrary.org)
  • In addition, the CXCR4 receptors are estimated to distribute on ~70% area of the cell surface. (spiedigitallibrary.org)
  • Is the Subject Area "B cell receptors" applicable to this article? (plos.org)
  • A, Western blot analyses of CXCR4 in whole cell lysates. (aacrjournals.org)
  • Histograms are shown for all cell lines used in this study, with the percentage of positive CXCR4 staining in parentheses. (aacrjournals.org)
  • We found that most of the available thyroid cancer cell lines express both the receptors, albeit to different extent, and AXL was always much more abundant than TYRO3. (unina.it)
  • The inhibition of TYRO3 and AXL by blocking reagents or RNA interference targeting each receptor or the ligand decreased cell proliferation and resistance to apoptotic stimuli in different thryoid cancer cell lines. (unina.it)
  • In cell lines that expressed both receptors and ligand, the simultaneous blockade of these molecules dramatically affected cell viability. (unina.it)
  • Finally, we found that the blockade of AXL receptor consistently impaired thyroid carcinoma cell line invasiveness through Matrigel and, moreover, it inhibited tumor growth in nude mice. (unina.it)
  • Further studies indicate that this inhibitory effect is not due to receptor antagonism but rather to bryostatin-5-induced receptor desensitization and down-regulation of cell surface CXCR4. (aacrjournals.org)
  • SYK or PI3K inhibition also selectively upregulated cell surface CXCR4 protein expression in BCR-dependent DLBCLs. (haematologica.org)
  • 1 Our previous studies demonstrated that a subset of DLBCLs rely upon B-cell receptor (BCR)-dependent survival signals. (haematologica.org)
  • CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. (pasteur.fr)
  • 1. An isolated stem cell, which is isolated by a method, comprising selecting the stem cell based on the stem cell exhibiting a CXCR4 receptor, demonstrating an affinity for the chemokine SDF-1, or both. (freepatentsonline.com)
  • and assessing tumor tropic potential of the stem cell based upon said expression level of CXCR4, said affinity for the chemokine SDF-1, or both. (freepatentsonline.com)
  • The pattern of expression of these chemokine receptors on T cell subsets and their regulation has important implications for AIDS pathogenesis and lymphocyte recirculation. (pnas.org)
  • Before its identity as a chemokine receptor was known, CXCR4 was shown to mediate entry of T cell line-tropic (T-tropic) HIV-1 strains ( 15 ), a process that subsequently was shown to be inhibited by SDF-1 ( 13 , 14 ). (pnas.org)
  • Traditionally, HIV isolates that use CXCR4 are known as T-cell tropic isolates. (thefullwiki.org)
  • Adsorption is attachment of the virus to a specific receptor on the host cell. (issuu.com)
  • The current study, is the first, to demonstrate a role for CXCR4 in the recruitment of cDC to the inflamed cornea, playing a direct role in dendritic cell homing after inflammation, making this receptor a potential target to modualte inflammatory responses in murine corneas. (arvojournals.org)
  • However, CXCL12 exposure induced TCam-2 cell invasion though simulated basement membrane, while in contrast, we provide the novel evidence that CXCR4-expressing non-seminoma cell lines 833ke and NTera2/D1 do not invade in response to CXCL12. (edu.au)
  • C) Quantification of the amount of PLA indicators per cell for CXCR4:ACKR3 relationships as with A. Ab ctrl. (labourlists.org)
  • D) FACS analyses of receptor cell surface area expression amounts in hVSMC after incubation using the 888216-25-9 TM peptides (100 M, 15 min at space temperature). (labourlists.org)
  • E) FACS analyses of receptor cell surface area manifestation after incubation hVSMC with non-targeting siRNA (solid blue collection) or siRNA particular for every receptor (solid red collection). (labourlists.org)
  • As demonstrated in Physique 1D, incubation of hVSMC using the TM peptide analogs didn't affect cell surface area expression degrees of CXCR4, ACKR3 or 1A-AR, in comparison to untreated hVSMC. (labourlists.org)
  • Mefloquine HCl Mefloquine HCl All features of CXCR4 rely on its cell-surface phrase vitally, which can be controlled by CXCR4 endocytosis, intracellular trafficking and recycling where possible in addition to gene phrase. (az628.com)
  • Two fairly well-studied procedures that regulate the amounts of cell-surface CXCR4 consist of ligand-dependent receptor endocytosis and the destruction of endocytosed receptors. (az628.com)
  • Objective To investigate the role and possible mechanism of Chemokine receptor CXCR4 in the drug resistance of sorafenib in renal cell carcinoma . (bvsalud.org)
  • Through binding to receptors, HIV-1 enters the cell by membrane fusion. (biomedcentral.com)
  • In this study, the ability of PMPs to deliver CXCR4 molecule to CXCR4-null targets (Daudi, K562 and U937 cell line) was evaluated and the different concentrations of PMPs were examined to transfer CXCR4. (ac.ir)
  • both lines were subjected to varying growth media and compounds previously reported to upregulate CXCR4 expression in other stem cell populations. (csuci.edu)
  • WHIM like mutations in CXCR4 were recently identified in patients with Waldenström's macroglobulinemia, a B-cell malignancy. (wikipedia.org)
  • A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell. (wikipedia.org)
  • These categories of cell surface receptors are prominently referred to as co-receptors. (wikipedia.org)
  • The CD receptor family typically act as co-receptors, illustrated by the classic example of CD4 acting as a co-receptor to the T cell receptor (TCR) to bind major histocompatibility complex II (MHC-II). (wikipedia.org)
  • Your search returned 1777 X-C motif chemokine receptor 1 Antibodies across 46 suppliers. (biocompare.com)
  • This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1 . (wikipedia.org)
  • The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization. (naver.com)
  • While G13 offers not really been demonstrated to regulate receptor trafficking previously, it can be very clear NF2 that G13 offers many important physical jobs. (az628.com)
  • Once the surface receptor binds the ligand it forms a complex with a corresponding surface receptor to regulate signalling. (wikipedia.org)
  • Even more specifically, we generated 8 loss-of-function (knock-out, KO) variations by replacing individual segments using their mouse counterparts, and 2 gain-of-function (knock-in, KI) by grafting individual MK-0359 IC50 regions in to the mouse molecule (Figs. 4A-B). Murine CXCR4 was chosen for producing the chimeric variations because it stocks ?90% sequence. (gasyblog.com)
  • In this study we demonstrate that apoptosis is induced upon HIV-I envelope binding to the chemokine receptor CXCR4. (cnrs.fr)
  • 10 The idea that the chemokine SDF-1 and its receptor play a functional role in nonhematopoietic tissues is supported by the the observation that SDF-1 −/− mice show impaired heart development. (bloodjournal.org)
  • Wilcoxon rank sum test was used to analyze the differential gene expressions of CXCL-12 and CXCR4 between gastric cancer tissues and normal gastric tissues. (cdc.gov)
  • There were differences between CXCL-12 and CXCR4 expression in 415 gastric cancer tissues and 35 normal gastric tissues. (cdc.gov)
  • Furthermore, we found that CXCR4 was overexpressed in ATC clinical samples, with respect to normal thyroid tissues by real-time PCR and immunohistochemistry. (unina.it)
  • Therefore, MEDI3185 interacts with CXCR4 with a definite mode of actions. (gasyblog.com)
  • The CD4 receptor in particular interacts with murine MHC-II following the "ball-on-stick" model, where the Phe-43 ball fits into the conserved hydrophobic α2 and β2 domain residues. (wikipedia.org)
  • Targeted deletion of CXCR4 or CXCL12 in mice confers embryonic lethality and exhibits defects in vascular and CNS development, hematopoiesis, and cardiogenesis ( 4 - 5 ). (pubmedcentralcanada.ca)
  • Our data demonstrated that troxerutin regulated the inflammatory lesions via CXCR4-TXNIP/NLRP3 inflammasome in the kidney of mice induced by BDE-47. (hindawi.com)
  • We previously found evidence that several miRNA molecules predicted to modulate CXCR4 signalling are differentially expressed during the differentiation of gonocytes into spermatogonia in mice. (edu.au)
  • Importantly, impaired blood flow in ischemic CXCR4 +/− mice was rescued by injection of wild-type BM-MNC. (ahajournals.org)
  • CXCR4 mutant mice have aberrant neuronal distribution. (wikipedia.org)