A subclass of receptor-like protein tryosine phosphatases that contain multiple extracellular immunoglobulin G-like domains and fibronectin type III-like domains. An additional memprin-A5-mu domain is found on some members of this subclass.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
An ephrin that was originally identified as the product of an early response gene induced by TUMOR NECROSIS FACTORS. It is linked to the CELL MEMBRANE via a GLYCOINOSITOL PHOSPHOLIPID MEMBRANE ANCHOR and binds EPHA2 RECEPTOR with high affinity. During embryogenesis high levels of ephrin-A1 are expressed in LUNG; KIDNEY; SALIVARY GLANDS; and INTESTINE.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A subcategory of protein tyrosine phosphatases that are bound to the cell membrane. They contain cytoplasmic tyrosine phosphatase domains and extracellular protein domains that may play a role in cell-cell interactions by interacting with EXTRACELLULAR MATRIX components. They are considered receptor-like proteins in that they appear to lack specific ligands.
An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
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.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.
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.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.
A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
A contactin subtype that is predominantly expressed in the CEREBELLUM; HIPPOCAMPUS; NEOCORTEX; and HYPOTHALAMUS.
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.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.
A transcriptional regulator in prokaryotes which, when activated by binding cyclic AMP, acts at several promoters. Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. Cell surface cyclic AMP receptors are not included (CYCLIC AMP RECEPTORS), nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins, which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Established cell cultures that have the potential to propagate indefinitely.
Agents that inhibit PROTEIN KINASES.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
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.
Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.
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 subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.
A subtype of non-receptor protein tyrosine phosphatase that is closely-related to PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1. Alternative splicing of the mRNA for this phosphatase results in the production at two gene products, one of which includes a C-terminal nuclear localization domain that may be involved in the transport of the protein to the CELL NUCLEUS. Although initially referred to as T-cell protein tyrosine phosphatase the expression of this subtype occurs widely.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
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.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A family of immunoglobulin-related cell adhesion molecules that are involved in NERVOUS SYSTEM patterning.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.
Proteins prepared by recombinant DNA technology.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
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.
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
The rate dynamics in chemical or physical systems.
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)
Adherence of cells to surfaces or to other cells.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
Physiologically inactive substances that can be converted to active enzymes.
Cell surface proteins that bind cyclic AMP with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized cyclic AMP receptors are those of the slime mold Dictyostelium discoideum. The transcription regulator CYCLIC AMP RECEPTOR PROTEIN of prokaryotes is not included nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
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.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Members of the src-family tyrosine kinases that are activated during the transition from G2 PHASE to M PHASE of the CELL CYCLE. It is highly homologous to PROTO-ONCOGENE PROTEIN PP60(C-SRC).
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A subcategory of protein tyrosine phosphatases that occur in the CYTOPLASM. Many of the proteins in this category play a role in intracellular signal transduction.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of a N-terminal catalytic domain and a large C-terminal domain that is enriched in PROLINE, GLUTAMIC ACID, SERINE, and THREONINE residues (PEST sequences). The phosphatase subtype is ubiquitously expressed and implicated in the regulation of a variety of biological processes such as CELL MOVEMENT; CYTOKINESIS; focal adhesion disassembly; and LYMPHOCYTE ACTIVATION.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A cell line derived from cultured tumor cells.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.
A subcategory of protein tyrosine phosphatases that contain SH2 type SRC HOMOLOGY DOMAINS. Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via their SH2 domain.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
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 lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
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.
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The relationship between the dose of an administered drug and the response of the organism to the drug.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing five different PDZ domains, and a carboxyl-terminal phosphatase domain. In addition to playing a role as a regulator of the FAS RECEPTOR activity this subtype interacts via its PDZ and FERM domains with a variety of INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
Elements of limited time intervals, contributing to particular results or situations.
The sum of the weight of all the atoms in a molecule.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A Janus kinase subtype that is predominantly expressed in hematopoietic cell. It is involved in signaling from a broad variety of CYTOKINE RECEPTORS including ones that utilize the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT.
Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
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.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.
Proto-oncogene proteins fes are protein-tyrosine kinases with a central SH2 DOMAIN. It has been implicated in SIGNAL TRANSDUCTION PATHWAYS for CELL DIFFERENTIATION of a variety of cell types including MYELOID PROGENITOR CELLS. Fes proto-oncogene proteins also bind TUBULIN and promote MICROTUBULE assembly.
A subclass of receptor-like protein tryosine phosphatases that contain a short extracellular domain, a cytosolic kinase-interaction domain, and single protein tyrosine kinase domain.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
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.
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.
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.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
Antibodies produced by a single clone of cells.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
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.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
A family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
Salts and esters of the 14-carbon saturated monocarboxylic acid--myristic acid.

Stromal cells mediate retinoid-dependent functions essential for renal development. (1/5686)

The essential role of vitamin A and its metabolites, retinoids, in kidney development has been demonstrated in vitamin A deficiency and gene targeting studies. Retinoids signal via nuclear transcription factors belonging to the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families. Inactivation of RARaplpha and RARbeta2 receptors together, but not singly, resulted in renal malformations, suggesting that within a given renal cell type, their concerted function is required for renal morphogenesis. At birth, RARalpha beta2(-) mutants displayed small kidneys, containing few ureteric bud branches, reduced numbers of nephrons and lacking the nephrogenic zone where new nephrons are continuously added. These observations have prompted us to investigate the role of RARalpha and RARbeta2 in renal development in detail. We have found that within the embryonic kidney, RARalpha and RARbeta2 are colocalized in stromal cells, but not in other renal cell types, suggesting that stromal cells mediate retinoid-dependent functions essential for renal development. Analysis of RARalpha beta2(-) mutant kidneys at embryonic stages revealed that nephrons were formed and revealed no changes in the intensity or distribution of molecular markers specific for different metanephric mesenchymal cell types. In contrast the development of the collecting duct system was greatly impaired in RARalpha beta2(-) mutant kidneys. Fewer ureteric bud branches were present, and ureteric bud ends were positioned abnormally, at a distance from the renal capsule. Analysis of genes important for ureteric bud morphogenesis revealed that the proto-oncogene c-ret was downregulated. Our results suggest that RARalpha and RARbeta2 are required for generating stromal cell signals that maintain c-ret expression in the embryonic kidney. Since c-ret signaling is required for ureteric bud morphogenesis, loss of c-ret expression is a likely cause of impaired ureteric bud branching in RARalpha beta2(-) mutants.  (+info)

VEGF is required for growth and survival in neonatal mice. (2/5686)

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.  (+info)

Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells. (3/5686)

We have investigated the effects of the truncated trkB receptor isoform T1 (trkB.T1) by transient transfection into mouse N2a neuroblastoma cells. We observed that expression of trkB.T1 leads to a striking change in cell morphology characterized by outgrowth of filopodia and processes. A similar morphological response was also observed in SH-SY5Y human neuroblastoma cells and NIH3T3 fibroblasts transfected with trkB.T1. N2a cells lack endogenous expression of trkB isoforms, but express barely detectable amounts of its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). The morphological change was ligand-independent, since addition of exogenous BDNF or NT-4 or blockade of endogenous trkB ligands did not influence this response. Filopodia and process outgrowth was significantly suppressed when full-length trkB.TK+ was cotransfected together with trkB.T1 and this inhibitory effect was blocked by tyrosine kinase inhibitor K252a. Transfection of trkB.T1 deletion mutants showed that the morphological response is dependent on the extracellular, but not the intracellular domain of the receptor. Our results suggest a novel ligand-independent role for truncated trkB in the regulation of cellular morphology.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (4/5686)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation. (5/5686)

The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma.  (+info)

Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. (6/5686)

Interaction between integrin alphavbeta3 and extracellular matrix is crucial for endothelial cells sprouting from capillaries and for angiogenesis. Furthermore, integrin-mediated outside-in signals co-operate with growth factor receptors to promote cell proliferation and motility. To determine a potential regulation of angiogenic inducer receptors by the integrin system, we investigated the interaction between alphavbeta3 integrin and tyrosine kinase vascular endothelial growth factor receptor-2 (VEGFR-2) in human endothelial cells. We report that tyrosine-phosphorylated VEGFR-2 co-immunoprecipitated with beta3 integrin subunit, but not with beta1 or beta5, from cells stimulated with VEGF-A165. VEGFR-2 phosphorylation and mitogenicity induced by VEGF-A165 were enhanced in cells plated on the alphavbeta3 ligand, vitronectin, compared with cells plated on the alpha5beta1 ligand, fibronectin or the alpha2beta1 ligand, collagen. BV4 anti-beta3 integrin mAb, which does not interfere with endothelial cell adhesion to vitronectin, reduced (i) the tyrosine phosphorylation of VEGFR-2; (ii) the activation of downstream transductor phosphoinositide 3-OH kinase; and (iii) biological effects triggered by VEGF-A165. These results indicate a new role for alphavbeta3 integrin in the activation of an in vitro angiogenic program in endothelial cells. Besides being the most important survival system for nascent vessels by regulating cell adhesion to matrix, alphavbeta3 integrin participates in the full activation of VEGFR-2 triggered by VEGF-A, which is an important angiogenic inducer in tumors, inflammation and tissue regeneration.  (+info)

Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation. (7/5686)

We have identified Socs1 as a downstream component of the Kit receptor tyrosine kinase signalling pathway. We show that the expression of Socs1 mRNA is rapidly increased in primary bone marrow-derived mast cells following exposure to Steel factor, and Socs1 inducibly binds to the Kit receptor tyrosine kinase via its Src homology 2 (SH2) domain. Previous studies have shown that Socs1 suppresses cytokine-mediated differentiation in M1 cells inhibiting Janus family kinases. In contrast, constitutive expression of Socs1 suppresses the mitogenic potential of Kit while maintaining Steel factor-dependent cell survival signals. Unlike Janus kinases, Socs1 does not inhibit the catalytic activity of the Kit tyrosine kinase. In order to define the mechanism by which Socs1-mediated suppression of Kit-dependent mitogenesis occurs, we demonstrate that Socs1 binds to the signalling proteins Grb-2 and the Rho-family guanine nucleotide exchange factors Vav. We show that Grb2 binds Socs1 via its SH3 domains to putative diproline determinants located in the N-terminus of Socs1, and Socs1 binds to the N-terminal regulatory region of Vav. These data suggest that Socs1 is an inducible switch which modulates proliferative signals in favour of cell survival signals and functions as an adaptor protein in receptor tyrosine kinase signalling pathways.  (+info)

Control of growth and differentiation by Drosophila RasGAP, a homolog of p120 Ras-GTPase-activating protein. (8/5686)

Mammalian Ras GTPase-activating protein (GAP), p120 Ras-GAP, has been implicated as both a downregulator and effector of Ras proteins, but its precise role in Ras-mediated signal transduction pathways is unclear. To begin a genetic analysis of the role of p120 Ras-GAP we identified a homolog from the fruit fly Drosophila melanogaster through its ability to complement the sterility of a Schizosaccharomyces pombe (fission yeast) gap1 mutant strain. Like its mammalian homolog, Drosophila RasGAP stimulated the intrinsic GTPase activity of normal mammalian H-Ras but not that of the oncogenic Val12 mutant. RasGAP was tyrosine phosphorylated in embryos and its Src homology 2 (SH2) domains could bind in vitro to a small number of tyrosine-phosphorylated proteins expressed at various developmental stages. Ectopic expression of RasGAP in the wing imaginal disc reduced the size of the adult wing by up to 45% and suppressed ectopic wing vein formation caused by expression of activated forms of Breathless and Heartless, two Drosophila receptor tyrosine kinases of the fibroblast growth factor receptor family. The in vivo effects of RasGAP overexpression required intact SH2 domains, indicating that intracellular localization of RasGAP through SH2-phosphotyrosine interactions is important for its activity. These results show that RasGAP can function as an inhibitor of signaling pathways mediated by Ras and receptor tyrosine kinases in vivo. Genetic interactions, however, suggested a Ras-independent role for RasGAP in the regulation of growth. The system described here should enable genetic screens to be performed to identify regulators and effectors of p120 Ras-GAP.  (+info)

TY - JOUR. T1 - Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions. AU - Weinger, Jason G.. AU - Omari, Kakuri M.. AU - Marsden, Kurt. AU - Raine, Cedric S.. AU - Shafit-Zagardo, Bridget. PY - 2009/7. Y1 - 2009/7. N2 - Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (⌈150 kd), and soluble Axl (80 kd) were ...
Buy Anti-MerTK (c-MER, c-Mer Proto-oncogene Tyrosine Kinase, MER, MER Receptor Tyrosine Kinase, MERK, ME, item number: M2995-05.100 from United States Biological at Biomol!
Mer receptor tyrosine kinase (Mer) signaling plays a central role in the intrinsic inhibition of the inflammatory response to Tolllike receptor activation. Previously, we found that lung Mer protein expression decreased after lipopolysaccharide (LPS) treatment due to enhanced Mer cleavage. The purpose of the present study was to examine whether pharmacologically restored membrane-bound Mer expression upregulates the Mer signaling pathways and suppresses lung inflammatory responses. Pretreatment with the ADAM17 (a disintegrin and metalloproteinase-17) inhibitor TAPI-0 (tumor necrosis factor alpha protease inhibitor-0) reduced LPS-induced production of soluble Mer protein in bronchoalveolar lavage (BAL) fluid, restored membrane-bound Mer expression, and increased Mer activation in alveolar macrophages and lungs after LPS treatment. TAPI-0 also enhanced Mer downstream signaling, including phosphorylation of protein kinase b, focal adhesion kinase, and signal transducer and activator of ...
The RON receptor tyrosine kinase regulates epithelial cell homeostasis and tumorigenesis by transducing multiple signals through its functional domains. The present study was to determine the significance of the entire C-terminus in RON or its variant RON160-mediated activities related to cell motility and tumorigenesis. Analysis of protein phosphorylation revealed that elimination of the entire C-terminus significantly impairs the ligand-dependent or independent RON or RON160 phosphorylation and dimerization. Phosphorylation of downstream signaling proteins such as Erk1/2, AKT, and p38 MAP kinase was also diminished in cells expressing the C-terminus-free RON or RON160. These dysfunctional activities were accompanied with the inability of truncated RON or RON160 to mediate cytoplasmic β-catenin accumulation. Functional analysis further demonstrated that truncation of the C-terminus significantly impairs RON or RON160-mediated cell proliferation, morphological changes, and cellular migration.
ALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance. To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib. Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association. Patients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3
Cancer is one of the most important life-threatening diseases in the world. The current efforts to combat cancer are being focused on molecular-targeted therapies. The main purpose of such approaches is based on targeting cancer cell-specific molecules to minimize toxicity for the normal cells. RON (Recepteur dOrigine Nantais) tyrosine kinase receptor is one of the promising targets in cancer-targeted therapy and drug delivery. ...
The elevated levels of inflammatory cytokines observed in the CNS upon chronic HIV-1 infection suggest that control of the cytokine network is compromised. We have previously demonstrated that RON, which limits macrophage inflammatory activities, is reduced in brains of end-stage HIV-1-infected individuals with evidence of encephalitis (7). In this study, we have used a progressive macaque SIV CNS disease model to show that over time RON expression is decreased in SIV-infected macaques and that this inversely correlates with inflammatory cytokine expression and brain disease. Furthermore, in vitro studies using primary tissue-resident macrophages confirm that RON initially limits HIV-1 transcription, but, over the course of infection, receptor expression is decreased.. The macaque SIV infection model provided an opportunity to explore when RON expression is decreased during infection and whether this correlates with other indicators of inflammation. The macaque model has been well characterized ...
Mice lacking the Axl receptor tyrosine kinase (RTK) and its family members exhibit detrimental effects on their reproductive ability. AXL is localized to Sertoli cells, which are the major nurturing cells in the seminiferous ...
Life Chemicals provided computational models for the human ALK kinases for its recent paper and designed a dedicated ALK Tyrosine Kinase Focused Library
The presence of RON and its variant isoform in malignant and non-malignant human colonic tissues was examined by immunohistochemistry using paraffin-embedded sections and RT-PCR analysis followed by direct sequencing of PCR product using RNAs isolated from frozen tissues. In normal colonic mucosa, R …
Lung cancer is the leading cause of death by cancer in North America. A decade ago, genomic rearrangements in the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase were identified in a subset of non-small cell lung carcinoma (NSCLC) patients. Soon after, crizotinib, a small molecule ATP-competitive ALK inhibitor was proven to be more effective than chemotherapy in ALK-positive NSCLC patients. Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, are approved for use as a first-line therapy in these patients, where ALK rearrangement is currently diagnosed by immunohistochemistry and in situ hybridization. The clinical success of these three ALK inhibitors has led to the development of next-generation ALK inhibitors with even greater potency and selectivity. However, patients inevitably develop resistance to ALK inhibitors leading to tumor relapse that commonly manifests in the form of brain metastasis. Several new approaches aim to overcome the various mechanisms of
Neuronal migration is a crucial process that allows neurons to reach their correct target location to allow the nervous system to function properly. AP-2α is a transcription factor essential for neural crest cell migration and its mutation results in apoptosis within this cell population, as demonstrated by genetic models. We down-modulated AP-2α expression in GN-11 neurons by RNA interference and observe reduced neuron migration following the activation of a specific genetic programme including the Adhesion Related Kinase (Axl) gene. We prove that Axl is able to coordinate migration per se and by ChIP and promoter analysis we observe that its transcription is directly driven by AP-2α via the binding to one or more functional AP-2α binding sites present in its regulatory region. Analysis of migration in AP-2α null mouse embryo fibroblasts also reveals an essential role for AP-2α in cell movement via the activation of a distinct genetic programme. We show that AP-2α plays an essential role in cell
Graduate Student. Receptor tyrosine kinase RON, besides being expressed on tumor cells is also expressed on host macrophages and epithelial cells. My project is focused on deciphering the role of Ron (receptor tyrosine kinase) expressing resident peritoneal macrophages in breast cancer metastasis. I am using immune competent in vivo mouse models to address this question. I am also interested in delineating the developmental origin of Ron expressing resident peritoneal macrophages. Contrary to the previously well-established dogma that all macrophages originate from bone marrow derived monocytes recent studies has shown embryonic origins of certain tissue resident macrophages. I am using in vivo lineage tracing models to address this question. And outside of the lab, I love kayaking. ...
Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1),
The KOMP Repository Collection is located at the MMRRC at the University of California, Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...
Cirrhosis of the liver is a condition with a high mortality and raising prevalence worldwide. Infectious complications are highly frequent and independent predictors of outcome in patients with cirrhosis - being the leading cause of decompensation, acute-on-chronic liver failure (ACLF) and death. There is no treatment option other than transplantation, applicable at early stages and to only a minority of patients. Susceptibility to infection has been documented in patients with cirrhosis and has been attributed to immuneparesis and monocyte dysfunction in the state of decompensation and liver failure. The underlying mechanisms are incompletely understood. Development of targeted immunomodulatory strategies might effectively reduce infectious complications and mortality in cirrhosis. MER receptor tyrosine kinase (MERTK), expressed on monocytes/macrophages, plays a pivotal role in dampening innate immune responses. We have recently discovered and documented the role of MERTK in innate immune ...
In general, tumors exhibit higher tyrosine kinase activity in comparison to normal tissues. This correlation is also reflective in tumor cells versus normal epithelial cells. Receptor tyrosine kinases modulate diverse processes involved in tumor progression and metastasis. Consequently, receptor tyrosine kinases are viewed as attractive targets for molecular therapy. An understanding of the molecular alterations that facilitate tumor progression and metastasis will provide insight into approaches to optimize targeted therapies. In this context, the role of the receptor tyrosine kinase RON in human epithelial cell malignancies is currently under active investigation. We have recently shown that the RON ligand, MSP, promotes the invasive phenotype of MDA-MB-231 and MDA-MB-468 cells and also identified the critical regulatory elements that are required for basal RON promoter activity and RON gene expression ( 24). We have followed up those studies in this article and showed that a chemopreventive ...
Describes how Anaplastic Lymphoma Receptor Tyrosine Kinase (ALK) mutation testing is used, when ALK mutation (gene rearrangement) testing is ordered, and what the results of ALK mutation testing might mean
The management of anaplastic lymphoma kinase rearranged (ALK+) non-small cell lung cancer (NSCLC) exemplifies the potential of a highlights the success of the precision medicine approach to cancer careparadigm. The ALK inhibitor crizotinib has demonstrated led to improved outcomes in the first and second line setting, however, toxicities, intracranial activity and acquired resistance necessitated the advent of later generation ALK inhibitors. A large portion of acquired resistance to ALK inhibitors is caused by secondary mutations in the ALK kinase domain. Alectinib is a second generation ALK inhibitor capable of overcoming multiple crizotinib resistant ALK mutations and has demonstrated improved outcomes after crizotinib failure, leading to approval in crizotinib treated ALK+ NSCLC patients. Favorable toxicity profile and improved intracranial activity haves spurred ongoing front line trials and comparisons to other ALK inhibitors. However, important questions regarding comparability to competitor
p,This chapter presents a general approach for the application of spatial intensity distribution analysis (SpIDA) to the pharmacodynamic quantification of receptor tyrosine kinase homodimerization in response to direct ligand activation or transactivation by G-protein-coupled receptors. Intensity histograms are generated from single fluorescence microscopy images. These histograms are then fit with Poissonian distributions to obtain density maps and quantal brightness values of the labeled proteins underlying the images. This approach allows resolving monomer/oligomer protein mixtures within subcellular compartments using conventional confocal laser scanning microscopy. The application of quantitative pharmacological analysis to data obtained using SpIDA provides a universal method for comparing studies between cell lines and receptor systems. In contrast to methods based on resonance energy transfer, SpIDA is suitable not only for use in recombinant systems but also for the characterization of ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
High-quality Axl proteins from ACROBiosystems. Various species and tags of Axl proteins. Minimal Batch-to-Batch Variation. Bulks in stock.
Background The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the merchandise from the t(2;5)chromosomal translocation within non-Hodgkins lymphoma. CNS by evaluation. However, furthermore to Mizolastine supplier appearance of DAlk in the mind, careful evaluation reveals anadditional early function for DAlk within the developing visceralmesoderm where its appearance is certainly coincident withactivated ERK. Bottom line Within this paper a Alk is described Mizolastine supplier by all of us RTK that is expressed within the developing embryonic mesoderm and CNS. Our data offer proof for the everyday living of a DAlk RTK pathway in hybridization research have uncovered ALK appearance within the developing anxious program and ALK happens to be a book orphan receptor tyrosine kinase thats suspected to try out important function in the standard advancement and function from the anxious system. Within this paper a homologue is certainly ...
Background The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the merchandise from the t(2;5)chromosomal translocation within non-Hodgkins lymphoma. CNS by evaluation. However, furthermore to Mizolastine supplier appearance of DAlk in the mind, careful evaluation reveals anadditional early function for DAlk within the developing visceralmesoderm where its appearance is certainly coincident withactivated ERK. Bottom line Within this paper a Alk is described Mizolastine supplier by all of us RTK that is expressed within the developing embryonic mesoderm and CNS. Our data offer proof for the everyday living of a DAlk RTK pathway in hybridization research have uncovered ALK appearance within the developing anxious program and ALK happens to be a book orphan receptor tyrosine kinase thats suspected to try out important function in the standard advancement and function from the anxious system. Within this paper a homologue is certainly ...
Leslie Duplaquet, Martin Figeac, Frédéric Leprêtre, Charline Frandemiche, Céline Villenet, Shéhérazade Sebda, Nasrin Sarafan-Vasseur, Mélanie Bénozène, Audrey Vinchent, Gautier Goormachtigh, Laurence Wicquart, Nathalie Rousseau, Ludivine Beaussire, Stéphanie Truant, Pierre Michel, Jean-Christophe Sabourin, Françoise Galateau-Sallé, Marie-Christine Copin, Gérard Zalcman, Yvan De Launoit, Véronique Fafeur and David Tulasne ...
Oncogenic fusions of anaplastic lymphoma kinase (ALK) define a subset of human lung adenocarcinoma. The 1st generation ALK inhibitor crizotinib demonstrated impressive clinical benefit in ALK-fusion positive lung cancers and was approved by the FDA for the treatment of ALK-fusion positive NSCLC in 2011. However, as seen with most kinase inhibitors, patients treated with crizotinib eventually develop resistance to therapy. Acquired ALK kinase domain mutations and disease progression in the central nervous system (CNS) are reported as main contributors to patient relapse after ALK inhibitor therapy. Preclinically, crizotinib lacks significant brain penetration and does not potently inhibit activity of ALK kinase domain mutants, so a drug discovery program was initiated aimed to develop a second generation ALK inhibitor that is more potent than existing ALK inhibitors, capable of inhibiting the resistant ALK mutants and penetrating the blood-brain-barrier. These objectives present a considerable ...
Brajendra K. Tripathi, View ORCID ProfileTiera Grant, Xiaolan Qian, Ming Zhou, Philipp Mertins, Dunrui Wang, Alex G. Papageorge, View ORCID ProfileSergey G. Tarasov, View ORCID ProfileKent W. Hunter, Steven A. Carr, View ORCID ProfileDouglas R. Lowy ...
TY - JOUR. T1 - Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. AU - Stommel, Jayne M.. AU - Kimmelman, Alec C.. AU - Ying, Haoqiang. AU - Nabioullin, Roustem. AU - Ponugoti, Aditya H.. AU - Wiedemeyer, Ruprecht. AU - Stegh, Alexander H.. AU - Bradner, James E.. AU - Ligon, Keith L.. AU - Brennan, Cameron. AU - Chin, Lynda. AU - DePinho, Ronald A.. PY - 2007/10/12. Y1 - 2007/10/12. N2 - Targeted therapies that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway have shown promising anticancer activity, but their efficacy in the brain tumor glioblastoma multiforme (GBM) and other solid tumors has been modest. We hypothesized that multiple RTKs are coactivated in these tumors and that redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. Tumor cell lines, xenotransplants, and primary tumors indeed show multiple ...
Objectif Préciser les aspects cliniques et évaluer lintérêt du traitement par endoprothèse JJ associant des antituberculeux plus ou moins un traitement corticoïde. Patients et méthodes De janvier 1992 à décembre 2001, 12 patients atteints de sténoses urétérales dorigine tuberculeuse ont bénéficié dune monté de sonde JJ pendant 12 semaines en moyenne, associant un traitement antituberculeux pendant 8 mois, et un traitement corticoïde dans deux cas. Il sagissait de 6 femmes et de 6 hommes, âgés de 20 à 73 ans (âge moyenne: 40 ans). Résultats Les manifestations cliniques les plus fréquentes étaient représentées par la douleur (66.66%) et lhématurie (41.6%). La sténose était unilatérale et unifocale dans 4 cas, unilatérale et bifocale dans 3 cas, sous forme duretère moniliforme dans 3 cas. Le rein contre-latéral était normal dans 9 cas et mastic dans 3 cas. La sténose était bilatérale dans 2 cas, a droite dans 6 cas et à gauche dans 4 cas. Lévolution a ...
keywords = {*Gene Expression Regulation, *Homeostasis, Bacteria, Bacteria/*immunology, Biological, Drosophila melanogaster/*immunology, Drosophila Proteins/biosynthesis/metabolism, Gene Expression Regulation, Homeostasis, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinases/metabolism, Models, NF-kappa B, NF-kappa B/metabolism, ras Proteins, ras Proteins/metabolism, Receptor Protein-Tyrosine Kinases, Receptor Protein-Tyrosine Kinases/metabolism ...
Drug resistance remains an elusive problem in cancer therapy, particularly with novel targeted therapy approaches. Much work is currently focused upon the development of an increasing arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops as therapies are continued over time. The current clinical paradigm after failure of first line ALK TKI is to administer another drug in the same class. As to which drug however, the answer is uncertain, as clinical evidence is lacking. To address this shortcoming, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK tyrosine kinase inhibitors used in clinic, and performed a collateral sensitivity analysis to each of the other drugs. We found that all of the ALK inhibitor resistant cell lines displayed a significant cross-resistance to all other ALK inhibitors. To test for the stability of the resistance phenotypes, we evaluated the ...
Drug resistance remains an elusive problem in cancer therapy, particularly with novel targeted therapy approaches. Much work is currently focused upon the development of an increasing arsenal of targeted therapies, towards oncogenic driver genes such as ALK-EML4, to overcome the inevitable resistance that develops as therapies are continued over time. The current clinical paradigm after failure of first line ALK TKI is to administer another drug in the same class. As to which drug however, the answer is uncertain, as clinical evidence is lacking. To address this shortcoming, we evolved resistance in an ALK rearranged non-small cell lung cancer line (H3122) to a panel of 4 ALK tyrosine kinase inhibitors used in clinic, and performed a collateral sensitivity analysis to each of the other drugs. We found that all of the ALK inhibitor resistant cell lines displayed a significant cross-resistance to all other ALK inhibitors. To test for the stability of the resistance phenotypes, we evaluated the ...
(2019) Noé et al. Journal of Thoracic Oncology. Introduction: The effectiveness of ALK receptor tyrosine kinase (ALK) inhibitors can be limited by the development of ALK resistance mutations. This exploratory analysis assessed the efficacy of alectinib in patients with NSCLC and ALK point mutatio...
Ensartinib, also known as X-396, is an orally available small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with potential antineoplastic activity. Upon oral administration, X-396 binds to and inhibits ALK kinase, ALK fusion proteins and ALK point mutation variants. Inhibition of ALK leads to the disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development.
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the echinoderm microtubule associated protein-like family. The encoded WD-repeat protein may be involved in microtubule formation. Abnormal fusion of parts of this gene with portions of the anaplastic lymphoma receptor tyrosine kinase gene, which generates EML4-ALK fusion transcripts, is one of the primary mutations associated with non-small cell lung cancer. Alternative splicing of this gene results in two transcript variants. [provided by RefSeq, Jan 2015 ...
Fig. 2. Standard diagnostic techniques are not optimal for the routine detection of ALK-rearranged NSCLC. Representative ALK-rearranged (A-F) and ALK germ-line (G-I) tumors analyzed by FISH using probes flanking the ALK gene (A, D, and G), standard immunohistochemical staining for ALK protein (B, E, and H), and tyramide-amplified immunohistochemical staining for ALK protein (C, F, and I). Red arrows, split FISH probes characteristic of an ALK rearrangement; yellow arrow, nonsplit FISH probes characteristic of ALK germ-line. ...
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the development of several human cancers and, as a result, is a recognized target for the development of small-molecule inhibitors for the treatment of ALK-positive malignancies. Here, we present the crystal structures of the unphosphorylated human ALK kinase domain in complex with the ATP competitive ligands PHA-E429 and NVP-TAE684. Analysis of these structures provides valuable information concerning the specific characteristics of the ALK active site as well as giving indications about how to obtain selective ALK inhibitors. In addition, the ALK-KD-PHA-E429 structure led to the identification of a potential regulatory mechanism involving a link made between a short helical segment immediately following the DFG motif and an N-terminal two-stranded beta-sheet. Finally, mapping of the activating mutations associated with neuroblastoma onto our structures may explain the roles these residues have in the activation process. ...
BMS-777607是一种Met相关的抑制剂,作用于c-Met,Axl,Ron和Tyro3,在无细胞试验中IC50分别为3.9 nM,1.1 nM,1.8 nM和4.3 nM,作用于Met相关靶点比作用于Lck, VEGFR-2,和TrkA/B选择性高40倍,比作用于其他受体和非受体激酶选择性高500多倍。Phase 1/2。. ...
Greg Lemke discovered a family of three receptor tyrosine kinases, called TAM receptors, which play a crucial role in telling immune cells how to handle infection from bacteria, viruses and other pathogens, as well as normal cellular debris. His lab showed how problems with the TAM receptors (called Axl, Mer and Tyro3) or their pathways are associated with increased levels of drug-resistant cancer as well as inflammation and autoimmune disease. Understanding how to separate the roles of each receptor could lead to new classes of drugs to fight viruses and bacteria. Aside from immune function, TAM receptors are involved in the healthy development of the nervous system. Lemke also focuses on another major family of receptor tyrosine kinases, called Eph receptors. These are one of the earliest to show up in the developing brain of a fetus and help to guide neuronal connections. Eph receptors help neurons-like those that link the eyes to the brain-know where to go as they grow.. ...
Receptor tyrosine kinase (RTK) inhibitors are frequently used to treat cancers and the results have been mixed, some of these small molecule drugs are highly successful while others show a more modest response. A high number of studies have been conducted to investigate the signaling mechanisms and corresponding therapeutic influence of RTK inhibitors in order to explore the therapeutic potential of RTK inhibitors. However, most of these studies neglected the potential metabolic impact of RTK inhibitors, which could be highly associated with drug efficacy and adverse effects during treatment. In order to fill these knowledge gaps and improve the therapeutic utilization of RTK inhibitors a large-scale computational simulation/analysis over multiple types of cancers with the treatment responses of RTK inhibitors was performed. The pharmacological data of all eight RTK inhibitor and gene expression profiles of 479 cell lines from The Cancer Cell Line Encyclopedia were used. The potential metabolic impact
Mice homozygous for the Axl knockout allele exhibit an overtly normal phenotype - however, in combination with mutations in other receptor tyrosine kinases, this strain may be useful in studies of innate immunity, autoimmunity, germ cell development and apoptosis. Axl is highly expressed by key cellular targets of ZIKA virus (ZIKV), and is proposed to promote viral entry in certain cell types (including non-Axl-expressing cells). Axl inhibition represents a potential approach for antiviral therapies.
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ROS1 (ROS proto-oncogene 1 , receptor tyrosine kinase), Authors: Samuel J Klempner, Sai-Hong Ou. Published in: Atlas Genet Cytogenet Oncol Haematol.
Celldex Therapeutics (previously Kolltan Pharmaceuticals) is developing monoclonal antibodies which target HER3 (or ERBB3) receptor tyrosine kinases (RTKs) for
Click to launch & play an online audio visual presentation by Dr. Daniela Krause on Small molecule inhibitors of receptor tyrosine kinases, part of a collection of online lectures.
Looking for online definition of AXL receptor tyrosine kinase in the Medical Dictionary? AXL receptor tyrosine kinase explanation free. What is AXL receptor tyrosine kinase? Meaning of AXL receptor tyrosine kinase medical term. What does AXL receptor tyrosine kinase mean?
TY - JOUR. T1 - Recurrence of anaplastic lymphoma kinase (ALK) positive adenocarcinoma after 17 years. T2 - Case report. AU - Al-Baimani, Khalid. AU - Sekhon, Harman S.. AU - Wheatley-Price, Paul. PY - 2015. Y1 - 2015. N2 - Introduction: About four to six percent of non-small cell lung cancer (NSCLC) harbor Anaplastic lymphoma kinase rearrangement (ALK). ALK positive NSCLC has a distinct clinicopathological features. In the advanced setting ALK tyrosine kinase inhibitors are used in the first and second line of treatment. However, less is known about the outcome of stage one ALK positive NSCLC. Presentation of case: Our case is a 58 year old man who presented initially with stage one ALK positive NSCLC. He relapsed 17 years later. Discussion: It is very unusual for stage one NSCLC to relapse beyond 10 years. It is surprising that our patient relapsed many years after his initial diagnosis. Conclusion: This may highlight a different biology and outcome. It may also mean a longer follow up is ...
This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, consent withdrawal or death. The study is expected to last approximately 42 months ...
A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants - NCT02075840
c met related tyrosine kinase antibody; CD136 antibody; CD136 antigen antibody; CDw136 antibody; Macrophage stimulating 1 receptor (c met related tyrosine kinase) antibody; Macrophage stimulating 1 receptor antibody; Macrophage stimulating protein receptor alpha chain antibody; MACROPHAGE STIMULATING PROTEIN RECEPTOR antibody; Macrophage stimulating protein receptor beta chain antibody; Macrophage-Stimulating 1 Receptor (MST1R) antibody; Macrophage-stimulating protein receptor beta chain antibody; MSP receptor antibody; Mst1r antibody; MST1R variant RON30 antibody; MST1R variant RON62 antibody; NPCA3 antibody; p185 RON antibody; p185-Ron antibody; Protein-tyrosine kinase 8 antibody; PTK 8 antibody; ptk8 antibody; PTK8 protein tyrosine kinase 8 antibody; Recepteur dorigine nantais (RON) antibody; RON antibody; RON protein tyrosine kinase antibody; RON variant E2E3 antibody; RON_HUMAN antibody; Soluble RON variant 1 antibody; Soluble RON variant 2 antibody; Soluble RON variant 3 antibody; Soluble ...
The CCAAT/enhancer-binding protein β (C/EBPβ) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK(+)). Although ALK-mediated C/EBPβ transcriptional activation has been reported, C/EB …
Neuroblastoma is a childhood extracranial solid tumour that is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly requires characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and R1464STOP), which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression, we have employed cell culture-based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position 1174 (F1174I
Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22-rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22-rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced ...
Concentrating on anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase receptor initially defined as a potent oncogenic driver in anaplastic large-cell lymphoma (ALCL) by means of nucleophosmin (NPM)-ALK fusion protein, using tyrosine kinase inhibitors shows to be always a appealing therapeutic approach for ALK-expressing tumors. not really well covered. Within this review, the molecular systems of cancers stem cells in mediating level of resistance to ALK inhibitors along with the current knowledge of the molecular issues in concentrating on ALK in ALK-expressing individual cancers is going to be talked about. gene aberrations [6,7]. For instance, the echinoderm microtubule-associated proteins like 4 (fusion was discovered in ~5% of non-small cell lung malignancies (NSCLC) [8,9]. Amplified or mutated was discovered in ~14% of neuroblastomas (NB), the most frequent and aggressive youth malignancy [10,11,12,13]. Up to now, many ALK inhibitors are in various levels of clinical examining and ...
Alt. Names/Synonyms: c-met-related tyrosine kinase; CD136; CDw136; macrophage stimulating 1 receptor (c-met-related tyrosine kinase); Macrophage-stimulating protein receptor; Macrophage-stimulating protein receptor alpha chain; Macrophage-stimulating protein receptor beta chain; MSP receptor; MST1R; p185-Ron; Protein-tyrosine kinase 8; PTK8; PTK8 protein tyrosine kinase 8; RON; soluble RON variant 1; soluble RON variant 2; soluble RON variant 3; soluble RON variant 4 ...
Anaplastic lymphoma kinase (ALK) is a receptor type tyrosine kinase that belongs to the insulin receptor superfamily. It is also known as anaplastic lymphoma receptor tyrosine kinase, Tcrz, CD246, and NBLST3. ALK is expressed in the central and peripheral nervous system at late embryonic stage, and plays an important role in brain development. The ALK gene is rearranged, mutated, or amplified in various tumors, including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. This monoclonal antibody (clone mAb16-39) elicits tyrosine phosphorylation of ALK in human neuroblastoma (SK-N-SH) cells. It also induces further phosphorylation of signal transfer molecules like insulin receptor substrate-1 (IRD-1).. ...
The overall response rate was significantly higher with Crizotinib than with chemotherapy ( 83.3% in the Crizotinib vs. 25.0% in the chemotherapy group, P less than 0.05 ); the disease control rates were 100% and 75%, respectively ( P less than 0.05 ...
β-catenin, the critical effector of the Wnt pathway, regulates a number of key processes during development including proliferation, differentiation and cell fate determination, as well as tissue homeostasis in adults. β-catenin is normally localized to the cell adhesion junctions in epithelial cells and its abnormal cytplasmic/nuclear stabilization drives uncontrolled transcription of target genes (including c-jun, cyclin D1, c-myc, survivin, and MMP-7) regulating cell proliferation, survival and cell adhesion.12 In view of its biological importance, it is not surprisingly that deregulation of β-catenin has been linked to the pathogenesis of a number of human cancers, particularly those with an epithelial cell origin.28 Illegitimate activation of β-catenin has also been reported in several types of hematopoietic cancers.19,29-31 Nevertheless, the functional status and biological role of β-catenin have never been investigated in ALK+ALCL. In this study, we found that β-catenin is ...
Background The wounding response relies on tightly regulated crosstalk between recruited fibroblasts and the collagenous extracellular matrix (ECM). Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor for fibrillar collagen expressed during pathologic scarring, for example wound healing, arthritis and cancer. We have previously shown that DDR2 phosphorylation drives key wounding responses in skin fibroblasts including proliferation, chemotactic migration and secretion of both metalloproteinases and fibrillar collagen. In this study we compared healing of cutaneous wounds in DDR2+/+ and DDR2-/- mice and analyzed specific fibroblast responses. Results Cutaneous wound healing was significantly delayed in DDR2-/- mice compared with DDR2+/+ animals. Reduced α-smooth muscle actin (αSMA) expression and matrix metalloproteinase 2 (MMP2) activity in the DDR2-/- wound extracts indicated defective recruitment of skin fibroblasts. DDR2-/- wounds showed decreased tensile strength during ...
The wounding response relies on tightly regulated crosstalk between recruited fibroblasts and the collagenous extracellular matrix (ECM). Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor for fibrillar collagen expressed during pathologic scarring, for example wound healing, arthritis and cancer. We have previously shown that DDR2 phosphorylation drives key wounding responses in skin fibroblasts including proliferation, chemotactic migration and secretion of both metalloproteinases and fibrillar collagen. In this study we compared healing of cutaneous wounds in DDR2+/+ and DDR2-/- mice and analyzed specific fibroblast responses. Cutaneous wound healing was significantly delayed in DDR2-/- mice compared with DDR2+/+ animals. Reduced α-smooth muscle actin (αSMA) expression and matrix metalloproteinase 2 (MMP2) activity in the DDR2-/- wound extracts indicated defective recruitment of skin fibroblasts. DDR2-/- wounds showed decreased tensile strength during healing, which correlated with a
Macrophage stimulating 1 receptor (c-met-related tyrosine kinase), encoded by the MST1R gene, is a cell-surface receptor that binds macrophage-stimulating protein (MSP). It was previously known as RON. The precursor protein is cleaved to generate the mature form, a heterodimer of disulfide-linked alpha and beta subunits. The beta subunit of MST1R/RON is phosphorylated at tyrosine residues upon activation by MSP. MST1R/RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation, and survival at the wound site. MST1R/RON is also known as CDw136, protein-tyrosine kinase 8 (PTK8), c-met-related tyrosine kinase, macrophage-stimulating protein receptor, MSP receptor, p185-Ron, CD136, MST1R variant RON30, MST1R variant RON62, and RON variant E2E3.. ...
The prognostic impact of minimal disseminated disease (MDD) and anti-anaplastic lymphoma kinase (ALK) antibody titer in children with ALK-positive anaplastic large cell lymphoma (ALCL) was reported...
Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011 ...
Patients harboring ALK rearrangement adenocarcinoma after acquired resistance to crizotinib and transformation to small-cell lung cancer: a case report You-cai Zhu,1 Xing-hui Liao,2 Wen-xian Wang,3 Chun-wei Xu,4 Wu Zhuang,5 Li-hua Zhong,4 Kai-qi Du,1 Yan-ping Chen,4 Gang Chen,4 Mei-yu Fang6 1Department of Chest Disease Diagnosis and Treatment Center, 2Department of Tumor Molecular Laboratory, Zhejiang Rongjun Hospital, Jiaxing, Zhejiang, 3Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 4Department of Pathology, Fujian Provincial Cancer Hospital, 5Department of Medical Thoracic Oncology, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, Fuzhou, 6Department of Comprehensive Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to
The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (> 5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7-60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation ...
Brigatinib (BGB) is a newly approved anaplastic lymphoma kinase (ALK) inhibitor. On April 28, 2017, BGB was approved by the U.S. FDA for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. The toxicity profile of BGB includes nausea, fatigue, diarrhea, elevated lipase, dyspno
Zhou YQ, He C, Chen YQ et al. (2003). Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 22 (2): 186-97. PMID 12527888. doi:10.1038/sj.onc.1206075. CS1 održavanje: Eksplicitna upotreba et al. (link) ...
Introduction Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (in stem cell-like properties and of lincROR and crizotinib resistance in NSCLC cells are yet to become elucidated. important part of lincROR in EMLCALK+ NSCLC. lincROR may serve as a potential restorative focus on to conquer chemotherapy level of resistance in EMLCALK+ NSCLC. ) is usually a transforming gene and a driver mutation in NSCLC, which has been identified to be closely associated with cancerogenesis and serves as a causative factor in patients with NSCLC.5,6 The resulting fusion protein preserves the complete intracellular portion of ALK, and therefore, NSCLC cells with this fusion protein are highly sensitive to AMD3100 irreversible inhibition ALK tyrosine kinase inhibition, which could restrain tumor proliferation and induce tumor apoptosis.7 Crizotinib, a specific ALK inhibitor, is beneficial for most patients with ALK-positive NSCLC but has no obvious therapeutic effect on a minority of ...
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1. Protein Tyrosine Kinase (PTK) family; mammalian Discoidin Domain Receptor 1 (DDR1) and homologs; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a member of the DDR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa ...
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1. Protein Tyrosine Kinase (PTK) family; mammalian Discoidin Domain Receptor 1 (DDR1) and homologs; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a member of the DDR subfamily, which are receptor tyr kinases (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa ...
Receptor tyrosine kinases have an individual transmembrane (TM) section thats usually assumed to try out a passive function in ligand-induced dimerization and activation from the receptor. and covalent cross-linking tests. Our findings tension the part of TM website relationships in ErbB receptor function, and perhaps for additional single-spanning membrane protein. Intro Receptor tyrosine kinases (RTKs) are transmembrane (TM) glycoproteins that contain a adjustable extracellular N-terminal website, an individual membrane spanning domains, and a big Mdk cytoplasmic portion made up of a juxtamembrane domains, the extremely conserved tyrosine kinase domains, and a C-terminal regulatory area. Biochemical and structural data concur in todays proven fact that ligand binding stimulates monomeric receptor dimerization and trans-autophosphorylation at described tyrosine residues through intrinsic kinase activity (Heldin, 1995 ; Weiss and Schlessinger, 1998 ; Hubbard, 1999 ). Whereas ligand-induced RTK ...
Growth arrest-specific 6, also known as GAS6, is a human gene coding for the Gas6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity. It was originally found as a gene upregulated by growth arrested fibroblasts. Gas6 is a gamma-carboxyglutamic acid (Gla) domain-containing protein thought to be involved in the stimulation of cell proliferation. Gas6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3. The presence of Gla needs a vitamin K-dependent enzymatic reaction that carboxylates the gamma carbon of certain glutamic residues of the protein during its production in the endoplasmic reticulum. GRCh38: Ensembl release 89: ENSG00000183087 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000031451 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: GAS6 growth arrest-specific 6. Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (Apr 1996). Characterization of Gas6, a member ...
The receptor tyrosine kinase AXL is a pathway that plays a crucial role in metastasis and chemoresistance. Overexpression of AXL has been associated with metastasis, recurrence, and chemoresistance in various cancer including ovarian cancer[16, 17]}. Targeting AXL is an attractive approach because it is overexpressed among patients with epithelial ovarian cancer and strongly associated with advanced stages, high grade cancer and shorter median survival time. AVB-S6-500 is a potent AXL inhibitor by binding to the ligand Gas6. Pre-clinical studies found that AVB-S6-500 was efficacious in ovarian cancer xenograft tumor models. Interventions which would increase the proportion of patients achieving pCR in this patient population could impact survival favorably and are of interest for study ...
Because DDR1 is an RTK, we investigated the role of its kinase activity in invadosome formation. We demonstrated, using nilotinib as an inhibitor as well as blocking antibodies, that DDR1 kinase activity is not necessary for the formation of linear invadosomes. This is in agreement with our previous observations. Indeed, we found that linear invadosomes already appear within 10 min of cell seeding on type I collagen, a kinetic that is not compatible with DDR autophosphorylation, a slow process requiring ,30 min before being detectable (Shrivastava et al., 1997; Vogel et al., 1997; Juin et al., 2012). Interestingly, it was previously shown that the role of DDR1 in promoting collective migration was also independent of its kinase activity (Hidalgo-Carcedo et al., 2011). In our hands, the lack of requirement for c-Src activity, demonstrated with both a pharmacological antagonist and the use of SYF cells, is also in line with these findings because it was shown that c-Src was necessary for the full ...
TY - JOUR. T1 - Ron is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. AU - Gaudino, Giovanni. AU - Follenzi, Antonia. AU - Naldini, Luigi. AU - Collesi, Chiara. AU - Santoro, Massimo. AU - Gallo, Kathleen A.. AU - Godowski, Paul J.. AU - Comoglio, Paolo M.. PY - 1994. Y1 - 1994. N2 - RON, a cDNA homologous to the hepatocyte growth factor (HGF) receptor gene (MET), encodes a putative tyrosine kinase. Here we show that the RON gene is expressed in several epithelial tissues as well as in granulocytes and monocytes. The major RON transcript is translated into a glycosylated single chain precursor, cleaved into a 185 kDa heterodimer (p185(RON)) of 35 (α) and 150 kDa (β) disulfide-linked chains, before exposure at the cell surface. The Ron,β-chain displays intrinsic tyrosine kinase activity in vitro, after immunoprecipitation by specific antibodies. In vivo, tyrosine phosphorylation of p185(RON) is induced by stimulation with macrophage stimulating protein (MSP), a ...
Discoidin Domain Receptor 2 Inhibits Fibrillogenesis of Collagen Type 1 Lucy Greetham Mark Nowey Britney Tappen Lauren Canova Casey Pham Learning Objectives • Identify the objectives of the paper (level 1- Remember) • Distinguish the advantages and disadvantages of in-vivo and in-vitro experimentation to study collagen. (level 2 - Understand) • Demonstrate ability to understand SPR techniques and interpret new data. (level 3 - Apply) • Design an experiment to test your hypothesis for the mechanism of cellular response to a change in DDR expression (level 6 - create) Objectives • What are the main objectives of this paper? - Show interaction between DDR2 and collagen type 1 - Study the binding kinetics - Determine how DDR2 effects fibrilogenesis Discoidin Domain Receptors (DDR1 and DDR2) • Widely expressed cell surface receptors, which bind and are activated by collagen • Activation results in downstream signaling which is known to regulates the ECM • Both bond the native triple ...
Rabbit Polyclonal antibody to AXL (AXL receptor tyrosine kinase)IgGy Antibody Selector - Quickly search hundreds of thousands of antibodies available for purchase from VWR by selecting common antibody features like antigen symbol and name, reactivity, clonality, conjugation, host, and other key factors. Antibodies used to identify and locate intracellular and extracellular proteins in common applications such as Western Blot, ELISA, ImmunoChemistry and Flow Cytometry are all available for your research.
Receptor proteins are located within the cell surface membrane, nucleus membrane or other cellular organelle membrane. They can bind to corresponding ligands to initiate cellular signaling pathways. For cell surface receptors, such as receptor tyrosine kinases, interleukin receptors and receptors of growth factors, they are usually subdivided into three domains, extracellular domain, transmembrane domain and intracellular domain. Receptor proteins form the largest family of biological targets. For example, GPCR (G protein coupled receptor) is the target of more than 50% of current drugs. GPCR family members share a unique structure with seven-transmembrane domains. Receptor tyrosine kinases are single transmembrane proteins. They are key regulators for normal cellular processes and also involved in developing many types of cancer. The extracellular part of receptor tyrosine kinases is responsible for binding to growth factors and cytokines. The intracellular domain has kinase activity. Many ...
Developed to target the anaplastic lymphoma kinase (ALK) mutation, Xalkori (crizotinib) was approved for a subset of non-small cell lung cancers. The ALK mutation is also present in more than half of anaplastic large-cel
WASHINGTON & CAMBRIDGE, Mass., Apr 20, 2010 (BUSINESS WIRE) --ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced results of preclinical studies on its investigational anaplastic lymphoma kinase (ALK) inhibitor - AP26113 - showing potent inhibition of the target protein and of mutant forms that are resistant to the first-generation ALK inhibitor, which currently is in clinical trials in patients with cancer. ARIAD scientists presented these data today at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D.C. Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as anaplastic large cell lymphoma. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy. An in vitro assay was used to identify mutations in ALK that confer resistance to the investigational dual Met/ALK inhibitor ...
A standard therapy for breast cancer is the use of receptor tyrosine kinase (RTK) inhibitors. RTKs efficiently target multiple receptors, including the Ron transmembrane receptor, whose activation leads to increased survival, migration, and angiogenesis through signaling pathways such as PI3K/Akt and NF-κB. Ron overexpression is correlated with increased metastasis and poor outcomes in patients. The only ligand for Ron is hepatocyte growth factor-like protein (HGFL), which is an endocrine factor secreted into the circulation from the liver. Published reports demonstrated that ectopic overexpression of HGFL in cancer cells leads to increased metastasis. However, no studies have examined the role of endogenous HGFL in Ron activation during tumor development and metastasis. We sought to test the hypothesis that HGFL is required for Ron receptor activation and mammary tumorigenesis. We utilized mice with mammary-specific Ron overexpression (MMTV-Ron), which develop mammary tumors with 100% ...
TY - JOUR. T1 - Tumor profiling of co-regulated receptor tyrosine kinase and chemoresistant genes reveal different targeting options for lung and gastroesophageal cancers. AU - Wu, Jianzhong. AU - Li, Shuchun. AU - Ma, Rong. AU - Sharma, Ashok Kumar. AU - Bai, Shan. AU - Dun, Boying. AU - Cao, Haixia. AU - Jing, Changwen. AU - She, Jin-Xiong. AU - Feng, Jifeng. PY - 2016/1/1. Y1 - 2016/1/1. N2 - The expression of a number of genes can influence the response rates to chemotherapy while genes encoding receptor tyrosine kinases (RTKs) determine the response to most targeted cancer therapies currently used in clinics. In this study, we evaluated seven genes known to influence chemotherapeutic response (ERCC1, BRCA1, RRM1, TUBB3, STMN1, TYMS, and TOP2A) and five RTKs (EGFR, ERBB2, PDGFRB, VEGFR1 and VEGFR2) in non-small cell lung cancer (NSCLC) and esophagus cancer (EC) and the data are compared to gastric cancer (GC) data reported previously. We demonstrate significant differences in the expression ...
FUNCTION: This gene encodes a precursor protein that is proteolytically cleaved to yield an alpha chain and a beta chain which form a membrane-spanning heterodimer. The encoded protein belongs to a family of cell-surface receptor tyrosine kinases involved in signaling from the cell surface to the intracellular environment. The binding of the encoded protein to its ligand, macrophage-stimulating protein, mediates several biological activities including wound healing, tumor immunity, macrophage activation and hematopoiesis as well as cell growth, motility, survival and adhesion. The protein encoded by this gene also functions in early development and the macrophage-mediated inflammatory response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013 ...
... to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that ... Unlike the receptor tyrosine kinases (RTKs), the second subgroup of tyrosine kinases, the non-receptor tyrosine kinases are ... Non-receptor tyrosine kinases do not contain only a tyrosine kinase domain, nRTKs also possess domains that mediate protein- ... Thirty-two non-receptor tyrosine kinases have been identified in human cells (EC Non-receptor tyrosine kinases ...
... cDNAs of human leukocyte tyrosine kinase receptor tyrosine kinase predict receptor proteins with and without a tyrosine kinase ... The protein encoded by this gene is a member of the ALK/LTK receptor family of receptor tyrosine kinases (RTKs) whose ligand is ... Krolewski JJ, Dalla-Favera R (1991). "The ltk gene encodes a novel receptor-type protein tyrosine kinase". EMBO J. 10 (10): ... Kozutsumi H, Toyoshima H, Hagiwara K, Yazaki Y, Hirai H (1994). "Human ltk receptor tyrosine kinase binds to PLC-gamma 1, PI3-K ...
The related to receptor tyrosine kinase (RYK) gene encodes the protein Ryk. The protein encoded by this gene is an atypical ... "Localization of two mouse genes encoding the protein tyrosine kinase receptor-related protein RYK". Mamm. Genome. 6 (4): 255-6 ... However, in contrast to other receptor tyrosine kinases the C-terminal domain of RYK is devoid of detectable kinase activity. ... Hovens CM, Stacker SA (1992). "RYK, a receptor tyrosine kinase-related molecule with unusual kinase domain motifs". Proc. Natl ...
... in tyrosine-protein kinase receptors; and in the programmed cell death protein 1 (PD1). Immunoglobulin V-set, subgroup InterPro ... Single-pass transmembrane proteins, All stub articles, Membrane protein stubs). ... V-set domains are found in diverse protein families, including immunoglobulin light and heavy chains; in several T-cell ... This article incorporates text from the public domain Pfam and InterPro: IPR013106 v t e (Protein domains, ...
Tyrosine-protein kinase receptor UFO is an enzyme that in humans is encoded by the AXL gene. The gene was initially designated ... The protein encoded by this gene is a member of the receptor tyrosine kinase subfamily. Although it is similar to other ... Overview of all the structural information available in the PDB for UniProt: P30530 (Tyrosine-protein kinase receptor UFO) at ... AXL is a cell surface receptor tyrosine kinase, part of the TAM family of kinases including TYRO3 and MERTK.[citation needed] ...
Non-receptor tyrosine-protein kinase TYK2. Protein-tyrosine phosphatases PTPN3 and PTPN4, enzymes that appear to act at ... Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins. Janus tyrosine ... kinases (JAKs), cytoplasmic tyrosine kinases that are non-covalently associated with the cytoplasmic tails of receptors for ... Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E. Caenorhabditis elegans protein phosphatase ptp-1. Chishti ...
"Assignment of the endothelial-specific protein receptor tyrosine kinase gene (TEK) to human chromosome 9p21". Genomics. 23 (2 ... Also known as TIE2, it is an angiopoietin receptor. The TEK receptor tyrosine kinase is expressed almost exclusively in ... TEK is closely related to the TIE receptor tyrosine kinase.) This receptor possesses a unique extracellular domain containing 2 ... "Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta". Oncogene. 8 (3): 663- ...
They signal through receptor tyrosine kinases and serine/threonine protein kinases. Several other biomolecules that have ... Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinase. In ... Whereas neurotrophic factors within the neurotrophin family commonly have a protein tyrosine kinase receptor (Trk), ... Later studies determined GDNF uses a receptor tyrosine kinase and a high-affinity ligand-binding co-receptor GFRα. GDNF has an ...
Tyrosine-protein kinase-like 7 also known as colon carcinoma kinase 4 (CCK4) is a receptor tyrosine kinase that in humans is ... Receptor protein tyrosine kinases transduce extracellular signals across the cell membrane. A subgroup of these kinases lack ... Banga SS, Ozer HL, Park SK, Lee ST (1997). "Assignment of PTK7 encoding a receptor protein tyrosine kinase-like molecule to ... "Organization of the human PTK7 gene encoding a receptor protein tyrosine kinase-like molecule and alternative splicing of its ...
Barbacid M, Lamballe F, Pulido D, Klein R (December 1991). "The trk family of tyrosine protein kinase receptors". Biochimica et ... stands for tropomyosin receptor kinase or tyrosine receptor kinase (and not "tyrosine kinase receptor" nor "tropomyosin-related ... Trk receptors All neurotrophins bind to a class of highly homologous receptor tyrosine kinases known as Trk receptors, of which ... Trk receptors dimerize in response to ligand, as do other tyrosine kinase receptors. These dimers phosphorylate each other and ...
Other examples of tyrosine kinase receptors include the insulin receptor, the IGF1 receptor, the MuSK protein receptor, the ... also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type ... The TrkB receptor is part of the large family of receptor tyrosine kinases. A "tyrosine kinase" is an enzyme which is capable ... of adding a phosphate group to certain tyrosines on target proteins, or "substrates". A receptor tyrosine kinase is a "tyrosine ...
The PI3K is activated by G protein-coupled receptors and tyrosine kinase receptors. Class I PI3Ks are heterodimeric molecules ... DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR). They are protein serine/threonine kinases. The ... Many other proteins have been identified that are regulated by PtdIns(3,4,5)P3, including Bruton's tyrosine kinase (BTK), ... "Cannabinoids protect astrocytes from ceramide-induced apoptosis through the phosphatidylinositol 3-kinase/protein kinase B ...
Tyrosine-protein kinase receptor TYRO3 is an enzyme that in humans is encoded by the TYRO3 gene. TYRO3 has been shown to ... Crosier PS, Freeman SA, Orlic D, Bodine DM, Crosier KE (1996). "The Dtk receptor tyrosine kinase, which binds protein S, is ... "The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases". Int. J. Biochem. Cell Biol. 37 (11): 2344 ... "Transforming activity of receptor tyrosine kinase tyro3 is mediated, at least in part, by the PI3 kinase-signaling pathway". ...
In general they are protein ligands for tyrosine kinase receptors; binding to the specific receptor yields autophosphorylation ... frostick) In sciatic motor neurons both CNTF receptor mRNA expression and CNTF receptor is increased after injury for a ... phosphorylation of tyrosine residues on proteins that participate in further downstream signaling to activate proteins and ... The Schwann cells that form the bands of Bungner at the distal injury site express NGF receptors as a guiding factor for the ...
"Phosphorylation of protocadherin proteins by the receptor tyrosine kinase Ret". Proceedings of the National Academy of Sciences ... This is corroborated by a large number of other interacting proteins including phosphatases, kinases, adhesion molecules and ... CS1: long volume value, Cell adhesion proteins, Single-pass transmembrane proteins, Cadherins). ... Clustered Pcdhs proteins are detected throughout the neuronal soma, dendrites and axons and are observed in synapses and growth ...
Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain ... Roskoski R (June 2004). "The ErbB/HER receptor protein-tyrosine kinases and cancer". Biochemical and Biophysical Research ... Histidine-specific protein kinases are structurally distinct from other protein kinases and are found in prokaryotes, fungi, ... Intracellular receptors, such as nuclear receptors and cytoplasmic receptors, are soluble proteins localized within their ...
... , also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is ... Furge KA, Zhang YW, Vande Woude GF (November 2000). "Met receptor tyrosine kinase: enhanced signaling through adapter proteins ... The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to ... which is then translated into a 1,390 amino-acid MET protein. MET is a receptor tyrosine kinase (RTK) that is produced as a ...
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene. Tyk2 was the first member of ... This gene encodes a member of the tyrosine kinase and, to be more specific, the Janus kinases (JAKs) protein families. This ... Velazquez L, Fellous M, Stark GR, Pellegrini S (July 1992). "A protein tyrosine kinase in the interferon alpha/beta signaling ... 1996). "Interaction of the c-cbl proto-oncogene product with the Tyk-2 protein tyrosine kinase". Biochem. Biophys. Res. Commun ...
... lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway ... A5 protein and receptor protein tyrosine phosphatase mu), an LDLa domain (low-density lipoprotein receptor class A) and a ... encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)". Oncogene. 14 (18): ... Lee HH, Norris A, Weiss JB, Frasch M (October 2003). "Jelly belly protein activates the receptor tyrosine kinase Alk to specify ...
Eph receptor tyrosine kinases and receptor protein tyrosine phosphatase beta". Curr. Opin. Neurobiol. 8 (1): 117-27. doi: ... Park S, Sánchez MP (1997). "The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three ... Chan J, Watt VM (Aug 1991). "eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases". Oncogene. 6 (6 ... This gene encodes a member of the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related ...
"The adaptor protein Nck links receptor tyrosine kinases with the serine-threonine kinase Pak1". The Journal of Biological ... ARG-binding protein 2γ, hepatitis B virus X protein, STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl ... PAK proteins, a family of serine/threonine p21-activated kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as ... Shin YJ, Kim YB, Kim JH (September 2013). "Protein kinase CK2 phosphorylates and activates p21-activated kinase 1". Molecular ...
"Interaction between G proteins and tyrosine kinases upon T cell receptor.CD3-mediated signaling". J. Biol. Chem. 270 (51): ... Shraga-Levine Z, Sokolovsky M (2000). "Functional coupling of G proteins to endothelin receptors is ligand and receptor subtype ... 1996). "The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families ... "Interaction of the G-protein G11alpha with receptors and phosphoinositidase C: the contribution of G-protein palmitoylation and ...
Nusse R, Xu YK (1998). "The Frizzled CRD domain is conserved in diverse proteins including several receptor tyrosine kinases". ... include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal-specific kinase (NSK2), and ROR1 and ROR2. The ... Frizzled proteins include cysteine-rich domain that is conserved in diverse proteins, including several receptor tyrosine ... Sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in ...
Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene is ... Chan J, Watt VM (August 1991). "eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases". Oncogene. 6 ... Tyrosine kinase receptors, All stub articles, Membrane protein stubs). ... Ephrin type-B receptor 2 is a protein that in humans is encoded by the EPHB2 gene. Ephrin receptors and their ligands, the ...
Kamakura S, Moriguchi T, Nishida E (1999). "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. ... The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. Several transcript variants have been ... ETS domain-containing protein Elk-4 is a protein that in humans is encoded by the ELK4 gene. This gene is a member of the Ets ... "Entrez Gene: ELK4 ELK4, ETS-domain protein (SRF accessory protein 1)". Chai Y, Chipitsyna G, Cui J, Liao B, Liu S, Aysola K, ...
January 2017). "A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome". Molecular Cell. 65 (2): 347 ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2019-05-12. "PSICQUIC View". ... CCDC60 is a candidate for phosphorylation by Protein kinase C. The initial methionine residue is predicted to be cleaved from ... "coiled-coil domain-containing protein 60 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-03-04. ...
Ronsin C, Muscatelli F, Mattei MG, Breathnach R (May 1993). "A novel putative receptor protein tyrosine kinase of the met ... 1997). "Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility". J. Clin. Invest. 99 ... 2004). "Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid ... It is related to the c-MET receptor tyrosine kinase. MST1R has been shown to interact with Grb2. GRCh38: Ensembl release 89: ...
"A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome". Molecular Cell. 65 (2): 347-360. doi: ... to map the PPIs between human receptor tyrosine kinases (RTKs) and phosphatases. By examining RNA-seq data from The Cancer ... This report was based on the two protein-protein interaction (PPI) approaches, the membrane yeast two-hybrid (MYTH) and the ... Zinc finger CCHC-type containing 18 (ZCCHC18) is a protein that in humans is encoded by ZCCHC18 gene. It is also known as Smad- ...
Kamakura S, Moriguchi T, Nishida E (1999). "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. ... which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and ... This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the ... downstream signaling processes of various receptor molecules including receptor tyrosine kinases, and G protein-coupled ...
"A family of proteins that inhibit signalling through tyrosine kinase receptors". Nature. 386 (6621): 181-6. Bibcode:1997Natur. ... This protein was also reported to participate in the recruitment of tyrosine kinase SYK. Alternatively spliced transcript ... This protein was found to interact with TYROBP/DAP12, a protein bearing immunoreceptor tyrosine-based activation motifs. ... are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase- ...
... adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. Most studies have looked at ... A number of tyrosine kinase inhibitors that target c-Src tyrosine kinase (as well as related tyrosine kinases) have been ... is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ...
Receptor tyrosine kinase inhibitors, Tissue agnostic antineoplastic agents). ... decreased protein level, decreased calcium, increased total cholesterol, increased creatinine, and decreased sodium) dry mouth ... Selpercatinib is a kinase inhibitor, meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from ...
Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription. Antiviral and ... CpG motifs-by pattern recognition receptors, such as membrane bound toll like receptors or the cytoplasmic receptors RIG-I or ... and they showed its active site contains tyrosine residues. Tan's laboratory isolated sufficient amounts of human beta ... cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 ...
CDC42, protein tyrosine kinase, phosphoinositide 3-kinase, and Src-family kinases then activate Arp2/3. This causes the ... Then, the bacteria induce their internalization into host cells via a receptor-mediated invasion mechanism.[citation needed] ... This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called ... Both rOmpA and rOmpB are members of a family of surface cell antigens (Sca) which are autotransporter proteins; they act as ...
"The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase ... Holsinger LJ, Ward K, Duffield B, Zachwieja J, Jallal B (2002). "The transmembrane receptor protein tyrosine phosphatase DEP1 ... Ren Y, Busch RK, Perlaky L, Busch H (May 1998). "The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with ... Ren Y, Busch RK, Perlaky L, Busch H (1998). "The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with ...
Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ... "Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop ... "A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle". ... "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ...
For example, the Na⁺-K⁺ pump interacts directly with Src, a non-receptor tyrosine kinase, to form a signaling receptor complex ... receptor (IP3R) in different intracellular compartments. Protein-protein interactions play a very important role in Na⁺-K⁺ pump ... membrane protein can also relay extracellular ouabain-binding signalling into the cell through regulation of protein tyrosine ... signals through ouabain-triggered protein phosphorylation events include activation of the mitogen-activated protein kinase ( ...
It acts as a highly selective allosteric inhibitor of non-receptor tyrosine-protein kinase 2 (TYK2). The chemical structure of ... October 2021). "Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 ... Non-receptor tyrosine kinase inhibitors, Triazoles, Cyclopropyl compounds, Pyridazines, Methoxy compounds, Carboxamides, All ...
... and with a hepatocyte growth factor-regulated tyrosine kinase substrate (HGS). The interactions with cytoskeletal proteins and ... HAP1 also interacts with other factors involved in vesicular trafficking including GABAA receptor, Rho-GEF, and HGS. Li XJ, Li ... Huntingtin-associated protein 1 (HAP1) is a protein which in humans is encoded by the HAP1 gene. This protein was found to bind ... This gene encodes a protein that interacts with huntingtin, with two cytoskeletal proteins (dynactin and pericentriolar ...
Leukemia 9:900-907 (1995) Lyn tyrosine kinase is essential for erythropoietin-induced differentiation of J2E erythroid cells. ... Blood 111: 1946-1950 (2008) Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin- ... appropriate Lyn activity is essential for normal erythropoiesis and Epo receptor signalling. Blood 122: 262-271 (2013) A ... EMBO Journal 18:5559-5566 (1999) Maturation of erythroid cells and erythroleukemia development are affected by the kinase ...
Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases (RTKs). These include all receptors for ... Project at the Institute of Medical Biology aimed at identifying all oncogenic alterations in all protein tyrosine kinase (PTK ... Among many other achievements, he and his team have co-discovered two groups of receptor tyrosine kinases. In some tumours, ( ... some receptor tyrosine kinases tend to be over-active, due to genetic changes. Ullrich is also Principal Investigator of ...
Tyrosine Kinases are a sub-class of the protein-kinase. Phosphorylation of proteins is a necessary step in transduction of ... The tyrosine kinase based transductions are enzymatic transferences of a phosphate group from an ATP molecule to a protein in ... Protein Kinases might get stuck in ' off ' position and inhibit the cell reproduction for good, or on the contrary might get ... The protein KIR2DL3 transduces inhibitory signals upon the ligand binding via an immune tyrosine-based inhibitory motif (ITIM) ...
"A receptor for activated C kinase is part of messenger ribonucleoprotein complexes associated with polyA-mRNAs in neurons". The ... Heterogeneous nuclear ribonucleoprotein G is a protein that in humans is encoded by the RBMX gene. This gene belongs to the ... "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity ... "Entrez Gene: RBMX RNA binding motif protein, X-linked". Hofmann Y, Wirth B (Aug 2002). "hnRNP-G promotes exon 7 inclusion of ...
Srinivasan S, Mahowald AP, Fuller MT (April 2012). "The receptor tyrosine phosphatase Lar regulates adhesion between Drosophila ... Mahowald was concerned as to why organisms have multiple, very similar, genes that encode for the same proteins with only a few ... but their genetic information cannot be organized and separated into chromosomes due to inhibition of cyclin-dependent kinase ... In Drosophila testicles, the Leukocyte-antigen-related (LAR) receptor tyrosine phosphatase targets selection and synapse ...
Lu demonstrated that glycolytic enzyme pyruvate kinase M2 (PKM2) acts as a protein kinase and phosphorylates histone H3 to ... In addition, he showed that activation of growth factor receptors, expression of K-Ras G12V and B-Raf V600E, and hypoxia induce ... where it binds to and activates tyrosine-phosphorylated -catenin and c-Myc, resulting in expression of glycolytic genes and ... "Metabolic Kinases Moonlighting as Protein Kinases". Trends in Biochemical Sciences. 43 (4): 301-310. doi:10.1016/j.tibs.2018.01 ...
"Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation ... His work in the field of cell signalling showed how RAS and other signalling proteins are involved in transmitting signals from ... His track record includes the discovery of the N-Ras oncogene , the identification of farnesylation of Ras proteins, and the ... Hancock, JF; Magee, AI; Childs, JE; Marshall, CJ (June 1989). "All ras proteins are polyisoprenylated but only some are ...
Minkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors ... afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth factor receptor 2 (Her2) and ... Receptor tyrosine kinase inhibitors, Chloroarenes, Fluoroarenes, Quinazolines, Phenol ethers, Tetrahydrofurans, Aromatic amines ... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ...
... are phosphorylated upon activation of a variety of receptors that signal via protein tyrosine kinases. Through interactions ... 2002). "CIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases". J. Biol. Chem. 277 (42): 39666-72. ... Signal transduction protein CBL-C is a protein that in humans is encoded by the CBLC gene. CBL proteins, such as CBLC, ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode: ...
... candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases ... Hirai H, Matsuda S (September 1999). "Interaction of the C-terminal domain of delta glutamate receptor with spectrin in the ... protein kinase A and protein kinase C phosphorylation sites and modulates Ca2+-dependent cleavage of spectrin and protein- ... Herrmann H, Wiche G (1987). "Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 ...
... the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation". Immunity. 13 (6): 817-27 ... Phosphoinositide 3-kinase adapter protein 1 is an enzyme that in humans is encoded by the PIK3AP1 gene. GRCh38: Ensembl release ... "Entrez Gene: PIK3AP1 phosphoinositide-3-kinase adaptor protein 1". Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using ... 2005). "Identification of B cell adaptor for PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases". FEBS ...
"Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat". Human Molecular Genetics. 9 (4): 645-51 ... This results in the lowered expression of reelin protein, essential for proper cortex lamination and cerebellum development. ... August 1996). "Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in ... of the leptin receptor, capable of weighing up to 1 kilogram (2.2 lb) - more than twice the average weight. Obese Zucker rats ...
... are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating ... and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for ... This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial ... Liu Y, Virshup DM, White RL, Hsu LC (November 2002). "Regulation of BRCA1 phosphorylation by interaction with protein ...
A notable class of kinase drug targets is the receptor tyrosine kinases which are essential enzymes that regulate cell growth; ... Protein kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... "Peptide inhibitors of protein kinases-discovery, characterisation and use". Biochimica et Biophysica Acta (BBA) - Proteins and ... For example, some protein kinase inhibitors have chemical structures that are similar to ATP, one of the substrates of these ...
... forms and is involved in some of the same signaling pathways but is a protein tyrosine-kinase. CRK (gene) has been shown to ... "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its ... The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase ... Adapter molecule crk is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. This ...
... "p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated ... Leitges M, Gimborn K, Elis W, Kalesnikoff J, Hughes MR, Krystal G, Huber M (June 2002). "Protein kinase C-delta is a negative ... SHIP1 can also interact with other inhibitory receptors and contribute to negative signaling. Overall, the protein functions as ... pathways independently on its catalytic activity by serving as a bridge for other proteins thereby regulate protein-protein ...
1994). "Activation and serine phosphorylation of the p56lck protein tyrosine kinase in response to antigen receptor cross- ... 1995). "Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig alpha/Ig beta immunoreceptor tyrosine activation ... 1994). "Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45". J. ... 1995). "Identification of the tyrosine phosphatase PTP1C as a B cell antigen receptor-associated protein involved in the ...
Ford OH, Gregory CW, Kim D, Smitherman AB, Mohler JL (November 2003). "Androgen receptor gene amplification and protein ... April 2016). "Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic ... The PIM kinase family is another potential target for selective inhibition. A number of related drugs are under development. It ... Loss of the retinoblastoma (RB) protein induces androgen receptor deregulation in castration-resistant prostate cancer by ...
Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The ... Yokoo T, Kitamura M (May 1996). "Antioxidant PDTC induces stromelysin expression in mesangial cells via a tyrosine kinase-AP-1 ... "Induction of the rat prodynorphin gene through Gs-coupled receptors may involve phosphorylation-dependent derepression and ... "Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s)". The Journal of General Virology. 80 ( ...
... proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton". The Journal of Cell Biology. ... "Abl interactor 1 promotes tyrosine 296 phosphorylation of mammalian enabled (Mena) by c-Abl kinase". The Journal of Biological ... Protein enabled homolog is a protein that in humans is encoded by the ENAH gene. ENAH has been shown to interact with ABI1, ZYX ... Ermekova KS, Zambrano N, Linn H, Minopoli G, Gertler F, Russo T, Sudol M (December 1997). "The WW domain of neural protein FE65 ...
Ras protein - reading frame - receptor (biochemistry) - receptor antagonist - receptor protein-tyrosine kinase - recombinant ... protein subunit - protein synthesis - protein targeting - protein translocation - protein-tyrosine kinase - protein-tyrosine- ... prostaglandin receptor - protein - protein biosynthesis - Protein Data Bank - protein design - protein expression - protein ... fusion oncogene protein G protein - G protein-coupled receptor - G3P - GABA - GABA receptor - GABA-A receptor - gag-onc fusion ...
Amyloid Precursor Protein+Tau+VEGF Receptor 1+Alpha-synuclein+Natriuretic Peptide Receptor A/GC-A+Ni (1). ... BMP4+VEGF Receptor 2+VEGF Receptor 1+TGF beta Receptor I+AMPK alpha 1+AMPK alpha 2+BMPR1A+BMPR1B+BMP (1). ... BMP4+VEGF Receptor 2+TGF beta Receptor I+BMPR1A+BMPR1B+BMPR2+ALK-1+Activin Receptor Type IA+Activin (1). ... ALK+LTK+VEGF Receptor 2+FGFR1+Met (c-Met)+TIE2+Activin A Receptor Type IB/ALK-4+H-ERG+SMEK2 (1). ...
Non-receptor tyrosine-protein kinase TYK2 (human). Find diseases associated with this biological target and compounds tested ...
Identified as a definitive diagnostic marker, key driver and therapeutic target for chordoma, a malignant tumor that arises from remnant notochordal cells lodged in the vertebrae ...
... which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer ... The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, ... The EGFR family: not so prototypical receptor tyrosine kinases. Cold Spring Harb Perspect Biol. 2014 Apr 1;6(4):a020768. doi: ... The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the ...
N2 - Protein tyrosine kinase-7 (PTK7) is a receptor protein tyrosine kinase (RPTK)-like molecule that contains a catalytically ... AB - Protein tyrosine kinase-7 (PTK7) is a receptor protein tyrosine kinase (RPTK)-like molecule that contains a catalytically ... Protein tyrosine kinase-7 (PTK7) is a receptor protein tyrosine kinase (RPTK)-like molecule that contains a catalytically ... abstract = "Protein tyrosine kinase-7 (PTK7) is a receptor protein tyrosine kinase (RPTK)-like molecule that contains a ...
Her4 protein (1131-ER) is manufactured by R&D Systems. Reproducible results in bioactivity assays. Learn More... ... Proto-oncogene-like protein c-ErbB-4; receptor tyrosine-protein kinase erbB-4; Tyrosine kinase-type cell surface receptor HER4 ... as a carrier protein to our recombinant proteins. Adding a carrier protein enhances protein stability, increases shelf-life, ... Because ErbB3 contains a defective kinase domain, the kinase domain of ErbB2 is responsible for initiating the tyrosine ...
We present the first case of simultaneous muscle-specific kinase antibody positive myaesthenia gravis and relapsing-remitting ... Receptor Protein-Tyrosine Kinases / immunology* * Receptors, Cholinergic / immunology* * Tomography, X-Ray Computed ... Muscle-specific kinase antibody positive myaesthenia gravis and multiple sclerosis co-presentation: a case report and ... We present the first case of simultaneous muscle-specific kinase antibody positive myaesthenia gravis and relapsing-remitting ...
... many are protein ligands that bind and modulate transmembrane receptor tyrosine kinases. [7] Known negative regulators are ... The candidate region contains a gene that encodes VEGF receptor 3 (VEGFR-3). Cervicofacial lymphatic VM further occurs in ... by the combined effects of a large number of positive and negative signals simultaneously transduced by numerous receptors. ...
Leukemia, myelogenous, chronic, BCR-ABL positive; Drug resistance; Drug monitoring, neoplasm; Receptor Protein-Tyrosine Kinases ... Receptor Protein-Tyrosine Kinases; Pyrimidines/therapeutic use; Antineoplastic agents/administration & dosage; Monitoring; ... Nilotinib is a BCR-ABL kinase, c-KIT, platelet-derived growth factor receptor (PDGFR) and ephrin receptor inhibitor.(17) It ... Importance of monitoring and early switch to second generation tyrosine kinase inhibitors for the prognosis of patients with ...
ErbB-3 class receptor binding GO:0043125 Interacting selectively and non-covalently with the protein-tyrosine kinase receptor ... Protein tyrosine kinase activity GO:0004713 Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine ... Protein tyrosine kinase activity GO:0004713 Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine ... Protein tyrosine kinase activity GO:0004713 Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine ...
Potentiation of B‐Cell Antigen Receptor‐mediated Signal Transduction by the Heterologous src Family Protein Tyrosine Kinase, ... Potentiation of B‐Cell Antigen Receptor‐mediated Signal Transduction by the Heterologous src Family Protein Tyrosine Kinase, ... Potentiation of B‐Cell Antigen Receptor‐mediated Signal Transduction by the Heterologous src Family Protein Tyrosine Kinase, ... Potentiation of B‐Cell Antigen Receptor‐mediated Signal Transduction by the Heterologous src Family Protein Tyrosine Kinase, ...
Pkinase_Tyr; Protein tyrosine kinase. pfam14575. Location:648 → 720. EphA2_TM; Ephrin type-A receptor 2 transmembrane domain. ... Pkinase_Tyr; Protein tyrosine kinase. pfam14575. Location:40 → 112. EphA2_TM; Ephrin type-A receptor 2 transmembrane domain. ... Pkinase_Tyr; Protein tyrosine kinase. pfam14575. Location:40 → 112. EphA2_TM; Ephrin type-A receptor 2 transmembrane domain. ... Pkinase_Tyr; Protein tyrosine kinase. pfam14575. Location:536 → 608. EphA2_TM; Ephrin type-A receptor 2 transmembrane domain. ...
Proto-oncogene tyrosine-protein kinase receptor Ret (RET). Target Class. Kinase. Family. Receptor Tyrosine Kinase. Official ... Related Group Members: Receptor Tyrosine Kinase ? DiscoveRx offers cell-based assays that target other members of this gene ...
108091007921 receptor tyrosine kinases Proteins 0.000 description 1 * 102000027656 receptor tyrosine kinases Human genes 0.000 ... 102000018899 Glutamate Receptors Human genes 0.000 description 1 * 108010027915 Glutamate Receptors Proteins 0.000 description ... 102000034433 acetylcholine receptors Human genes 0.000 description 2 * 108020000715 acetylcholine receptors Proteins 0.000 ... 108091007928 VEGF receptors Proteins 0.000 description 1 * 102000009484 Vascular Endothelial Growth Factor Receptors Human ...
"Tyrosine Protein Kinase Receptor Market" report is to provide the newest industry data and Tyrosine Protein Kinase Receptor ... Global Tyrosine Protein Kinase Receptor Market 2017: Merck, Takara Bio Company, Sino Biological Inc, R&D Systems. The purpose ... allowing consumers to identify the Tyrosine Protein Kinase Receptor market Application, Type, Manufacturers and Regions, ... Tyrosine Protein Kinase Receptor market Forecast up to 2022.. View full press release ...
Receptor tyrosine kinase (RTK) adaptor proteins. 2885 (GRB2). BRITE hierarchy. SSDB. Ortholog. Paralog. Gene cluster. GFIT. ... 01521 EGFR tyrosine kinase inhibitor resistance. 2885 (GRB2). 01522 Endocrine resistance. 2885 (GRB2). 09180 Brite Hierarchies ... 04660 T cell receptor signaling pathway. 2885 (GRB2). 04662 B cell receptor signaling pathway. 2885 (GRB2). 04664 Fc epsilon RI ... 09182 Protein families: genetic information processing. 04131 Membrane trafficking [BR:hsa04131]. 2885 (GRB2). Membrane ...
... and anaplastic lymphoma kinase (ALK) are mutually exclusiv... ... Mutations in epidermal growth factor receptor (EGFR), KRAS, ... Entrectinib and its major metabolite inhibit tropomyosin receptor tyrosine kinases (TRKs), proto-oncogene tyrosine-protein ... The role of human EGFR2 (HER2), a member of the ERBB family of tyrosine kinase receptors, has been studied for NSCLC. The first ... Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non- ...
Protein EphA4 receptor tyrosine kinases [47774] (1 species). *. Species Mouse (Mus musculus) [TaxId:10090] [47775] (1 PDB entry ... d1b0xa_ a.60.1.2 (A:) EphA4 receptor tyrosine kinases {Mouse (Mus musculus)} ... 4-5 helices; bundle of two orthogonally packed alpha-hairpins; involved in the interactions with DNA and proteins. ... Class a: All alpha proteins [46456] (226 folds). *. Fold a.60: SAM domain-like [47768] (14 superfamilies). ...
Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature 1992; 355:78-80.. 55. Ozawa ... Alternatively, CSE may interact with the SCF receptor c-Kit, a member of type III receptor tyrosine kinase family found on MC. ... Stimulation of high affinity IgE Fc receptors (FcεRI) on MCs activates the tyrosine kinases, Lyn and Syk, and causes tyrosine ... Ca(2+)-dependent and Ca(2+)-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic ...
Kamakura, S., Moriguchi, T. & Nishida, E. Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. ... Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem 271, 16586-16590 (1996). ... Big mitogen-activated kinase regulates multiple members of the MEF2 protein family. Journal of Biological Chemistry 275, 18534- ... Big mitogen-activated protein kinase 1 protects cultured rat aortic smooth muscle cells from oxidative damage. Journal of ...
SYK is a non-receptor protein tyrosine kinase that is widely expressed in hematopoietic cells; ... Precisio Kinase, baculovirus infected Sf9 cells, ≥ 70% SDS-PAGE, buffered aqueous glycerol solution); ... SYK is a non-receptor protein tyrosine kinase that is widely expressed in hematopoietic cells. It is involved in coupling ... PRECISIO® Kinase, recombinant, expressed in baculovirus infected Sf9 cells, ≥70% (SDS-PAGE), buffered aqueous glycerol solution ...
Specialization: Cell signaling in particular in receptor tyrosine kinases, protein modification; Mouse and cell culture-based ... Specialization: Uncovering the role of the genetic mutations in the extracellular matrix protein ACLP/AEBP1 in Ehlers-Danlos ... Specialization: Regulatory mechanisms underlying the interactions between the metabolic pathway of protein N-glycosylation and ... Specialization: Virology; Identifying and characterizing host proteins that are cleaved by viral proteases ...
Klein, R., Parada, L.F., Coulier, F., and Barbacid, M. (1989). trkB, a novel tyrosine protein kinase receptor expressed during ... and a truncated receptor, TrkB.T1. While TrkB.T1 lacks the canonical tyrosine kinase domain, BDNF binding to this receptor is ... The full-length receptor, TrkB.FL, possesses a tyrosine kinase domain that autophosphorylates with BDNF binding, ... The two isoforms are distinguishable given that the full-length receptor contains exons for the tyrosine kinase domain, while ...
Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein ... Orthologous to human SHC2 (SHC adaptor protein 2).. Go Annotations in Tabular Form (Text View) (GO Graph) Filter annotations by ... SHC (Src homology 2 domain containing) transforming protein 2. MGI:106180 Go Annotations as Summary Text (Tabular View) (GO ... tyrosine kinase signaling pathway. Predicted to be active in plasma membrane. Is expressed in several structures, including ...
Receptor tyrosine kinases (RTKs) function through protein kinase entities located in the intracellular domain of each protomer ... The cell-surface receptors possessing intrinsic tyrosine kinase activity (RTK) minimally require a dimeric state for their full ... Receptor tyrosine kinases generally act by forming phosphotyrosine-docking sites on their own endodomains that propagate ... The Trk family is composed of three principal members (A, B and C), also termed neurotrophin tyrosine kinase receptors (NTRK1, ...
Tyrosine kinase receptor indistinguishable from the c-met protein. Giordano, S., Ponzetto, C., Di Renzo, M. F., Cooper, C. S. ...
The KIT gene provides instructions for making a member of a protein family called receptor tyrosine kinases. Learn about this ... The KIT gene provides instructions for making a member of a protein family called receptor tyrosine kinases. Receptor tyrosine ... Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor. Biochem Biophys Res Commun. 2005 Nov 11;337(1):1-13. ... The KIT protein is found in the cell membrane of certain cell types where a specific protein, called stem cell factor, attaches ...
... is a protein tyrosine kinase. Ligand binding to the PDGFR leads to tyrosine phosphorylation of numerous intracellular proteins ... Ligand binding to the PDGFR leads to tyrosine phosphorylation of numerous intracellular proteins, including the receptor itself ... PDGF-AA binds to αα receptors, PDGF-AB binds to αα and αβ receptors, and PDGF-BB binds to αα, αβ, and ββ receptors. This ... PDGF-AA binds to αα receptors, PDGF-AB binds to αα and αβ receptors, and PDGF-BB binds to αα, αβ, and ββ receptors. This ...
Non-receptor tyrosine-protein kinase TYK2 [5-1181] TargetNon-receptor tyrosine-protein kinase TYK2 [5-1181](Mus musculus). TBA ... TargetNon-receptor tyrosine-protein kinase TYK2 [5-1181](Mus musculus). TBA. Curated by ChEMBL. ... TargetNon-receptor tyrosine-protein kinase TYK2 [5-1181](Mus musculus). TBA. Curated by ChEMBL. ... TargetNon-receptor tyrosine-protein kinase TYK2 [5-1181](Mus musculus). TBA. Curated by ChEMBL. ...
  • Initial studies with the EGFR tyrosine kinase inhibitors (TKIs) gefitnib (Iressa) and erlotinib (Tarceva) demonstrated biologic and clinical activity in only a relatively limited subset of lung cancers. (medscape.com)
  • We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. (elsevier.com)
  • Tyrosine kinase inhibitors are a type of targeted therapy. (cancer.net)
  • Treatment with tyrosine kinase inhibitors, including dasatinib (Sprycel), midostaurin (PKC412, recently approved by the FDA for the treatment of systemic mastocytosis), and less commonly imatinib (Gleevec) and nilotinib (Tasigna), may be considered for patients with mast cells that have a mutation in the c-kit tyrosine kinase receptor. (cancer.net)
  • A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
  • 2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. (guidetopharmacology.org)
  • We are using new mouse models of prostate cancer for testing the efficacy of novel PIM1 kinase inhibitors in treating prostate cancer and reversing therapeutic resistance. (northwestern.edu)
  • The clinical success of multitargeted kinase inhibitors has stimulated efforts to identify promiscuous drugs with optimal selectivity profiles. (proteopedia.org)
  • Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. (proteopedia.org)
  • The paucity of Kit staining in malignant mesothelioma suggests these tumors are unlikely to respond to currently available tyrosine kinase inhibitors. (duke.edu)
  • Nonsmall-cell lung cancer accounts for 85% of all cases of the disease, and patients who respond to epidermal growth-factor receptor (EGFR) kinase inhibitors generally have the adenocarcinoma subtype of the disease. (medscape.com)
  • Then we asked if there were any existing protein kinase inhibitors that could inhibit the growth of squamous cell lung cancers harboring DDR2 mutations," he added. (medscape.com)
  • The EGFR gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. (medlineplus.gov)
  • Lung cancers with EGFR gene mutations tend to respond to treatments that specifically target the overactive epidermal growth factor receptor protein that allows cancer cells to constantly grow and divide. (medlineplus.gov)
  • The EGFR family: not so prototypical receptor tyrosine kinases. (medlineplus.gov)
  • Most studies have looked at the receptor tyrosine kinases and examples of these are platelet derived growth factor receptor (PDGFR) pathway and epidermal growth factor receptor (EGFR). (wikipedia.org)
  • Mutations in epidermal growth factor receptor ( EGFR ), KRAS, and anaplastic lymphoma kinase ( ALK ) are mutually exclusive in patients with NSCLC, and the presence of one mutation in lieu of another can influence response to targeted therapy. (medscape.com)
  • Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. (elsevier.com)
  • It is related to epidermal growth factor receptor (EGFR) and has high homology with other members of the EGFR family, which include ErbB-1, ErbB-3 and ErbB-4 as well. (indianjcancer.com)
  • HER2 (human epidermal growth factor receptor 2) is a transmembrane tyrosine kinase receptor and a member of the ErbB protein family (ie, the epidermal growth factor receptor [EGFR] family). (medscape.com)
  • The patient did not harbor an EGFR mutation, Dr. Meyerson pointed out, but was subsequently found to have a DDR2 kinase domain mutation. (medscape.com)
  • Non-small cell lung cancer (NSCLC): Participants whose tumors have a known sensitizing epidermal growth factor receptor (EGFR) mutation must also have experienced disease progression (during or after treatment) or have an intolerance to treatment with an EGFR tyrosine kinase inhibitor(s). (who.int)
  • The main purpose of this study is to evaluate the safety and efficacy of Apatinib in combination with Gefitinib as compared to placebo in combination with Gefitinib in participants with stage B-IV Non-squamous non-small-cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation (Del19 and L858R). (centerwatch.com)
  • Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). (wikipedia.org)
  • Lyn is activated by stimulation of B-cell receptor, which leads to the recruitment and phosphorylation of Zap70-related nRTK, Syk. (wikipedia.org)
  • The most common theme in nRTKs and RTK regulation is tyrosine phosphorylation. (wikipedia.org)
  • With few exceptions, phosphorylation of tyrosines in the activation loop of nRTKs leads to an increase in enzymatic activity. (wikipedia.org)
  • hex) release and mitogen-activated protein kinase (MAPK) phosphorylation. (ispub.com)
  • This process, called phosphorylation, leads to the activation of a series of proteins in multiple signaling pathways. (medlineplus.gov)
  • Ligand binding to the PDGFR leads to tyrosine phosphorylation of numerous intracellular proteins, including the receptor itself. (bdbiosciences.com)
  • Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis. (drugbank.com)
  • Our studies suggest that full activity of Nyk/Mer kinase requires phosphorylation of all three tyrosine residues in the kinase domain (Tyr-749, Tyr-753, and Tyr-754) and that Nyk kinase activity is modulated by the level of autophosphorylation in the kinase domain. (elsevier.com)
  • Activation of these receptors results in phosphorylation and subsequent activation of a series of kinases, including Rho family members, like Rac and CDC42, MLKs, and MEKKs. (biolegend.com)
  • We found that activation of the Met receptor for hepatocyte growth factor results in the tyrosine phosphorylation of β4, which is instrumental for integrin-mediated recruitment of the tyrosine phosphatase Shp2. (rupress.org)
  • When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). (proteopedia.org)
  • Serine or tyrosine phosphorylation can affect protein interactions (Yip et al. (atlasgeneticsoncology.org)
  • In both cell types, antigen recognition triggers the tyrosine phosphorylation of two key adaptor proteins, LAT and SLP-76. (technion.ac.il)
  • Epidermal growth factor receptor binds to at least seven different ligands. (medlineplus.gov)
  • The binding of a ligand to epidermal growth factor receptor allows the receptor to attach to another nearby epidermal growth factor receptor protein (dimerize), turning on (activating) the receptor complex. (medlineplus.gov)
  • In summary, extracellular signal-regulated kinase activation is required for many transcription factor responses to lysophosphatidic acid and epidermal growth factor, however it is not synergistic. (ersjournals.com)
  • Overexpression of the epidermal growth factor receptor family genes, which include ErbB-1, 2, 3 and 4, has been implicated in a number of cancers. (indianjcancer.com)
  • The alpha and gamma subunits are members of the kallikrein protein family, and while the role of the alpha subunit is unknown, the gamma subunit is an epidermal growth factor (EGF) binding protein and has a role in the functions of the beta subunit. (intechopen.com)
  • Genentech) is a recombinant humanized monoclonal antibody that targets an epitope in the extracellular domain of the human epidermal growth factor receptor 2 (HER2) protein. (elsevier.com)
  • Genistein inhibits protein tyrosine kinases including epidermal growth factor receptor kinase, binds to PPAR γ and estrogen receptors and acts as an agonist at GPER. (fishersci.com)
  • PTP1B dephosphorylates and inactivates a number of receptor protein tyrosine kinases, including the EGF (epidermal growth factor) and PDGF (platelet-derived growth factor) receptors and therefore can exert a suppressive action on growth factor cell signaling (Haj et al. (atlasgeneticsoncology.org)
  • In B cells, SYK plays a crucial role in intracellular signal transduction induced by oxidative stress as well as antigen receptor engagement.SYK has been shown to act as a potential tumor suppressor in breast cancer. (sigmaaldrich.com)
  • Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. (medlineplus.gov)
  • We report here that p53 uses a novel binding mechanism to regulate the transcription of epithelial cell kinase (ECK), a receptor protein-tyrosine kinase implicated in signal transduction. (cdc.gov)
  • HER2 is a member of a family of four transmembrane receptor tyrosine kinases that regulate cell growth, survival, and differentiation via multiple signal transduction pathways. (elsevier.com)
  • Unlike the receptor tyrosine kinases (RTKs), the second subgroup of tyrosine kinases, the non-receptor tyrosine kinases are cytosolic enzymes. (wikipedia.org)
  • HASM cells grown in vitro proliferate in response to a variety of stimuli, including G protein-coupled receptor (GPCR) agonists as well as peptide growth factors acting via receptor tyrosine kinases (RTKs) 1 , 2 . (ersjournals.com)
  • Next, luteolin was found to decrease the protein levels of all three TAM RTKs in the A549 and A549/CisR cells in a dose‑dependent manner. (spandidos-publications.com)
  • TAM RTKs also play important roles in immune regulation, since they function as phagocytic receptors in normal tissues ( 3 , 4 ). (spandidos-publications.com)
  • In addition, structural features of TAM RTKs in the extracellular, transmembrane and cytoplasmic kinase domains are very similar ( 3 ), which allow them to share various ligands including growth arrest-specific 6 (Gas6), protein S, tubby and tulip. (spandidos-publications.com)
  • Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). (prospecbio.com)
  • We found that multiple alternate receptors provided protection from FGFR inhibition, including receptor tyrosine kinases (RTKs), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), and hepatocyte growth factor receptor (MET). (elsevier.com)
  • and transmembrane receptor protein tyrosine kinase signaling pathway. (nih.gov)
  • Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. (jax.org)
  • Zika virus is able to evade the immune response with the help of NS proteins inhibiting the signaling pathway responsible for activation of IFN and ISG. (medscape.com)
  • The LH receptor/cAMP/PKA signaling pathway leads to the induction of specific genes (broken lines) in the androstenedione biosynthetic pathway. (endotext.org)
  • In grownup AML, IL-6 additionally upregulates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in stem cells and blood cell progenitors. (chores4kids.com)
  • The prM and E proteins facilitate viral attachment to the host cell membrane AXL receptor, a transmembrane receptor tyrosine kinase protein. (medscape.com)
  • Unlike receptor tyrosine kinases, nRTKs lack receptor-like features such as an extracellular ligand-binding domain and a transmembrane-spanning region. (wikipedia.org)
  • These gene changes result in a receptor protein that is constantly turned on (constitutively activated), even when it is not bound to a ligand. (medlineplus.gov)
  • Ligand binding results in receptor dimerization, with the PDGF type (AA, AB or BB) influencing the resulting PDGFR subunit composition (αα, αβ, or ββ). (bdbiosciences.com)
  • Co-receptors stabilize interactions between the TCR and its ligand, the peptide-major histocompatibility complex (pMHC), and enhance Ca 2+ signaling and T cell activation. (mdpi.com)
  • When the portion of DDR1 that sits outside of the cell membrane binds to another specific protein, known as its ligand, the kinase portion inside the cell becomes activated and can fuel cell growth. (cancer.gov)
  • Bone marrow cells from pAML sufferers expressing excessive ranges of IL-6 and IL-6 receptors had been cultured in human bone marrow stromal cells (HS-5 cells), which replicate the patterns of bone marrow stromal cell expression akin to secretion of IL-6, IL-1β, the ligand for receptor-type protein-tyrosine kinase (KIT), and macrophage/granulocyte colony-stimulating elements M-CSF, G-CSF, and GM-CSF. (chores4kids.com)
  • DDR2, which is a receptor tyrosine kinase that binds collagen as its endogenous ligand, has been previously reported to promote cell migration, proliferation, and survival. (medscape.com)
  • When antigen binds to T-cell receptor, Lck becomes autophosphorylated and phosphorylates the zeta chain of the T-cell receptor, subsequently another nRTK, Zap70, binds to this T-cell receptor and then participates in downstream signaling events that mediate transcriptional activation of cytokine genes. (wikipedia.org)
  • The structure of the catalytic domain can be divided into a small and a large lobe, where ATP binds to the small lobe and the protein substrate binds to the large lobe. (wikipedia.org)
  • The KIT protein is found in the cell membrane of certain cell types where a specific protein, called stem cell factor, attaches (binds) to it. (medlineplus.gov)
  • That is, PDGF-AA binds to αα receptors, PDGF-AB binds to αα and αβ receptors, and PDGF-BB binds to αα, αβ, and ββ receptors. (bdbiosciences.com)
  • When it finds the protein, the antibody binds to the cancer cell, effectively turning it into a target. (medicalnewstoday.com)
  • Phospho-CSF-1R/M-CSF-R (Tyr723) (49C10) Rabbit mAb specifically binds to phosphorylated M-CSF receptors, but not other phosphorylated protein tyrosine kinases. (cellsignal.com)
  • The p75NTR is a pan-neurotrophin receptor and, in addition to NGF, binds to other neurotrophins, such as BDNF, NT-3, and NT-4/5. (intechopen.com)
  • The protein, DDR1, is a cell-growth protein that binds to collagen proteins, which have a fiber-like structure. (cancer.gov)
  • The extracellular domain binds to the monomorphic region of MHC class II to increase the affinity of the T cell receptor to the antigen peptide-MHC class II complex [ 3 , 4 ]. (biomedcentral.com)
  • For example, specific domains that target enzymes to the cytoplasmic part of cytokine receptors (Jak family) or two domains: an integrin-binding domain and a focal adhesion-binding domain (Fak family). (wikipedia.org)
  • CD2 cytoplasmic domain binding protein. (embl.de)
  • Upon activation of Axl by Gas6 binding, tyrosine residues of the cytoplasmic tyrosine kinase domain are autophosphorylated ( 6 ), which in turn activate several signaling pathways mediating cell growth, survival, proliferation, migration and inhibition of apoptosis ( 3 , 7 ). (spandidos-publications.com)
  • Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. (proteopedia.org)
  • A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. (wikipedia.org)
  • One of the important domain of nRTKs is the tyrosine kinase catalytic domain, which is about 275 residues in length. (wikipedia.org)
  • c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (wikipedia.org)
  • The determination of the first protein sequence (insulin) was a landmark achievement that confirmed proteins were composed of a specific order of amino acid residues and lead to the development of methods, many eventually automated, for the rapid sequence analysis of a wide variety of proteins. (researchgate.net)
  • We also studied a series of Nyk mutants in which the three tyrosine residues were replaced individually, in pairs, or all together by phenylalanine. (elsevier.com)
  • Targeted therapy is a treatment that targets the disease's specific genes, proteins, or the tissue environment unique to mastocytosis that contribute to its growth and survival. (cancer.net)
  • To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors involved in your mastocytosis. (cancer.net)
  • The affected genes include the oncogenic transcription factor Fra2 (located on 2p23), the HLH protein Id2 (2p25), and the oncogenic tyrosine kinase CSF1-receptor (5q33.1). (mdc-berlin.de)
  • One observation that's particularly illustrative may be the altered amount of transcription of over 900 genes (2-fold transformation in appearance), following deletion of (a PPIP5K homologue) in person in the inositol phosphate kinase signaling family members. (immune-source.com)
  • The researchers conducted a systematic screening in which all protein tyrosine kinase genes were analyzed for somatic mutations in 290 specimens of squamous cell cancer. (medscape.com)
  • We found mutations in several kinase genes, including the DDR2 gene, and mutations were found in 11 of the 290 squamous cell cases, for a total of 3% to 4%," said Dr. Meyerson. (medscape.com)
  • This antibody has been reported to inhibit PDGF receptor-binding and mitogenic effects of PDGF-AB and -BB. (bdbiosciences.com)
  • Conversely, some co-receptors can dampen Ca 2+ signaling and inhibit T cell activation. (mdpi.com)
  • Some cancer therapies, such as imatinib (Gleevec) and erlotinib (Tarceva) , inhibit the activity of overly active tyrosine kinases. (cancer.gov)
  • Here we report the systematic discovery of molecules that potently inhibit both tyrosine kinases and phosphatidylinositol-3-OH kinases, two protein families that are among the most intensely pursued cancer drug targets. (proteopedia.org)
  • When cells were pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI) anchored receptors or with herbimycin-A to inhibit tyrosine-kinase activity, little morphological change was noted when chrysotile was added. (cdc.gov)
  • These medications inhibit cytokines, which are proteins that promote inflammation. (medlineplus.gov)
  • Abcam: antibodies, proteins, kits. (abcam.com)
  • Antibodies are proteins made by white blood cells. (medicalnewstoday.com)
  • Both chrysotile and crocidolite asbestos increased kinase activities associated with p60 Src or p120 focal adhesion kinase (FAK) factor as indicated by immunoprecipitations with selective monoclonal antibodies. (cdc.gov)
  • The Research Pack contains all you need for mouse proBDNF research: Antibodies to proBDNF and its receptor, and recombinant proteins all in one economical package! (alomone.com)
  • We have found antibodies against these cytokine receptors that are especially good in treating psoriasis. (medlineplus.gov)
  • (1) This gene fusion codes for a chimeric protein, BCR-ABL, which is associated with the uncontrolled activity of ABL tyrosine kinase (TK). (scielo.br)
  • Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers. (nih.gov)
  • pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. (wikipedia.org)
  • It belongs to a family of Src family kinases and is similar to the v-Src (viral Src) gene of Rous sarcoma virus. (wikipedia.org)
  • Two transcript variants encoding the same protein have been found for this gene. (wikipedia.org)
  • The KIT gene provides instructions for making a member of a protein family called receptor tyrosine kinases. (medlineplus.gov)
  • KIT gene mutations associated with GISTs create a protein that no longer requires binding of the stem cell factor protein to be activated. (medlineplus.gov)
  • More than 80 percent of individuals with systemic mastocytosis have a mutation in the KIT gene that replaces the protein building block (amino acid) aspartic acid with the amino acid valine at position 816 in the protein (Asp816Val or D816V). (medlineplus.gov)
  • This and other KIT gene mutations result in production of altered proteins that are constitutively activated. (medlineplus.gov)
  • Next, JNK proteins translocate to the nucleus where they interact with transcription factors including c-Jun and p53 to modulate gene expression resulting in apoptosis, cell migration, proliferation, or inflammation. (biolegend.com)
  • Ectopic expression of Axl was observed to attenuate the antiproliferative effect of luteolin, while knockdown of the Axl protein level using a gold nanoparticle-assisted gene delivery system increased its cytotoxicity. (spandidos-publications.com)
  • [1] , [2] The gene is located on chromosome 17q21 and encodes a 185 kDa protein. (indianjcancer.com)
  • We have a strong interest in genomics and gene regulation, oncogenic kinases as potential molecular therapeutic targets and the use of in vivo lineage tracing to define the fates of specific cell populations in tumorigenesis. (northwestern.edu)
  • Real-time PCR on EDTA blood targeting the gene for the major outer membrane protein lip L32 of human pathogenic Leptospira spp. (cdc.gov)
  • HER2-positive status is indicated by evidence of protein overexpression or gene amplification. (medscape.com)
  • Up to now, research in to the biology of inositol phosphate kinases continues to be well-served by hereditary research, including gene knock-outs both in microorganisms and cultured cells. (immune-source.com)
  • c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. (wikipedia.org)
  • DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in molecular function (MF) terms. (researchsquare.com)
  • SRC_CHICK ] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. (proteopedia.org)
  • In hematopoietic cells, the MAPK extracellular signal-regulated kinase-5 (ERK5), through the transcription factor MEF2, induces expression of miR-23 that inhibits KEAP-1 mRNA leading to NRF2 activation 11 . (nature.com)
  • One key proliferative signalling mediator is the extracellular signal-regulated kinase (ERK), a member of the mitogen-activation protein kinase (MAPK) family, and both LPA and EGF signal through ERK in many cell types 6 , 7 . (ersjournals.com)
  • Part of the MAPK family, c-Jun N-terminal kinases, or JNKs, respond to inflammatory cytokines, growth factors, and other cellular stress. (biolegend.com)
  • We investigated the role of mitogen-activated protein kinase (MAPK) family, a critical enzyme in cellular signaling, in normal and abnormal renal development. (nii.ac.jp)
  • Extracellular signal-regulated kinase (ERK), p38 MAPK (p38), and MAPK phosphatase-1 (MKP-1) are strongly expressed in the developing kidney, and JNK is detected predominantly in the adult kidney. (nii.ac.jp)
  • IgG1 bispecific antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity targeting HER2 and HER3 receptors. (ncats.io)
  • The role of human EGFR2 (HER2), a member of the ERBB family of tyrosine kinase receptors, has been studied for NSCLC. (medscape.com)
  • HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including lung, breast, gastric and colorectal cancers. (miscw.com)
  • 2+: Equivocal for HER2 protein expression - Complete membrane staining that is either nonuniform or weak in intensity but has circumferential distribution in at least 10% of cells. (medscape.com)
  • 0 or 1+: Negative for HER2 protein expression. (medscape.com)
  • The signaling pathways stimulated by the KIT protein control many important cellular processes such as cell growth and division (proliferation), survival, and movement (migration). (medlineplus.gov)
  • As a result, the KIT protein and the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of ICCs, leading to GIST formation. (medlineplus.gov)
  • Activation of the inhibitory guanine nucleotide-binding protein and of ERK signalling pathways were required for most transcription factor responses to LPA. (ersjournals.com)
  • 2 These tumors produce an altered form of the MET protein, which is a receptor tyrosine kinase that activates a wide range of cellular signaling pathways that can lead to cancer growth. (businesswire.com)
  • Nerve growth factor has two receptors, p75NTR and tyrosine kinase A (Trk A), whose signaling pathways can be synergic, antagonistic or independent of each other [ 5 ]. (intechopen.com)
  • It induces the NFκB and c-Jun kinase transduction pathways with varying effects depending on the pathway. (intechopen.com)
  • Within the multitude of signaling pathways aberrantly regulated in CLL the homeostatic axis composed by the chemokine receptor CCR7 and its ligands is the main driver for directing immune cells to home into the LN. In this literature review, we address the roles of CCR7 in the pathophysiology of CLL, and how this chemokine receptor is of critical importance to develop more rational and effective therapies for this malignancy. (frontiersin.org)
  • Moreover, the CyTOF evaluation indicated that distinct genomic subtypes of pAML having excessive IL-6 and IL-6 receptor ranges have frequent pathways of receptor-mediated inflammatory signaling. (chores4kids.com)
  • Focused sequencing recognized 5 recurrent areas of somatic mutations, together with numerous translocations and rearrangements that activated frequent STAT-mediated sign transduction and phosphoinositide-3-kinase-protein (PI3K) signaling pathways. (chores4kids.com)
  • [ 1 ] Activation of this class of cellular receptors is known to result in increased activity of a variety of molecular pathways associated with tumor growth and progression. (medscape.com)
  • Our group studies the regulatory mechanisms that govern adaptor protein signaling pathways. (technion.ac.il)
  • We present the first case of simultaneous muscle-specific kinase antibody positive myaesthenia gravis and relapsing-remitting multiple sclerosis to be reported in the English literature along with the inherent diagnostic and treatment challenges. (nih.gov)
  • Of 19 cases of myaesthenia with relapsing-remitting multiple sclerosis, nine (47%) were acetylcholine receptor antibody negative, but there were no previously published cases with muscle-specific kinase antibody. (nih.gov)
  • MC may be activated immunologically by cross-linking of multivalent antigen (allergen) with specific IgE antibody attached to the MC membrane via its high affinity receptor, FcεRI. (ispub.com)
  • The first prong helps the antibody to locate a unique protein called receptor tyrosine kinase ROR1, which is present on the surface of cancer cells but not healthy cells. (medicalnewstoday.com)
  • One reason for Prof. Rader deciding to engineer a bi-specific antibody based on receptor tyrosine kinase ROR1 is because, as he and his co-authors note in their paper, the protein "is expressed by numerous cancers and is largely absent from postnatal healthy cells and tissues. (medicalnewstoday.com)
  • The same membrane was stripped and reprobed with Phospho-Tyrosine Monoclonal Antibody (P-Tyr-100) (lower). (cellsignal.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in tissue homogenates, cell lysates and other biological fluids. (1elisakits.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in samples from tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (1elisakits.com)
  • Renowned as the #1 antibody event in the industry, this year's agenda boasts 15 dedicated topic streams, 3 unmissable training course add-on options and will bring together more than 700 of the antibody and protein community. (cshlpress.org)
  • The TAM family of receptor protein tyrosine kinases comprises three known members, namely Tyro3, Axl, and Mer. (edu.au)
  • In a similar manner, in H460 and H460/CisR cells, the protein levels of Axl and Tyro3 were decreased following luteolin treatment. (spandidos-publications.com)
  • The TAM receptor tyrosine kinase (RTK) family, consisting of Tyro3, Axl, MerTK is a subfamily of RTK, which has been reported to be involved in cell growth, proliferation, metastasis and resistance to chemotherapy ( 2 ) in various types of cancers. (spandidos-publications.com)
  • MERTK, a member of the TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases, has complex and diverse roles in cell biology. (elsevier.com)
  • T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca 2+ ) concentration. (mdpi.com)
  • The receptor contains seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular splited tyrosine kinase domain. (prospecbio.com)
  • The other family of medications targets an intracellular signaling molecule that is a tyrosine kinase. (medlineplus.gov)
  • Protein tyrosine kinase-7 (PTK7) is a receptor protein tyrosine kinase (RPTK)-like molecule that contains a catalytically inactive tyrosine kinase domain. (elsevier.com)
  • Nyk/Mer receptor tyrosine kinase is a new member of the Ufo/Axl tyrosine kinase family and is characterized by its neural cell adhesion molecule-like extracellular domain. (elsevier.com)
  • Here, the molecule appears to orchestrate the alignment of collagen proteins into dense barriers that block immune cells from coming into tumors , the researchers reported in Nature on November 3. (cancer.gov)
  • Disease relevance of STAP2 STAP- 2 was identical to a recently cloned adaptor molecule, BKS, a substrate of BRK ( breast tumor kinase) tyrosine kinase, although its function is still unknown. (wikigenes.org)
  • This work would create new small molecule drugs that would cross inside the membrane rather than bind to an outside receptor. (bonesbrigaderecords.com)
  • CHIR 99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR 99021 specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases[2]. (dcchemicals.com)
  • ErbB-2 is a transmembrane growth factor receptor belonging to the type I receptor tyrosine kinase family of proteins. (indianjcancer.com)
  • Here, we describe cloning and expression analysis of the zebrafish fibroblast growth factor receptor 1 ( fgfr1). (zfin.org)
  • RM 2BEH161 - A molecular model of fibroblast growth factor receptor 2 (FGFR2), a protein which plays an important role in embryonic development and tissue repair by mediating cell devision, growth and differentiation. (alamy.com)
  • In this work, we examined the disruption of the enterohepatic fibroblast growth factor 15/19 (FGF15/19)-fibroblast growth factor receptor 4 (FGFR4) endocrine axis during bacterial infections of the enterohepatic system. (biomedcentral.com)
  • Signaling to hepatic target cells occurs through the interaction of FGF15/19 with the tyrosine kinase receptor fibroblast growth factor receptor 4 (FGFR4) and also requires the protein βKlotho. (biomedcentral.com)
  • Our laboratory has previously shown that some gefitinibinsensitive head and neck squamous cell carcinoma (HNSCC) cell lines exhibit dominant autocrine fibroblast growth factor receptor (FGFR) signaling. (elsevier.com)
  • Absence of SYK protein in primary breast tumors is correlated with poor outcomes. (sigmaaldrich.com)
  • Scientists have identified a protein that may help prevent immune cells from entering breast tumors and killing the cancer cells. (cancer.gov)
  • DDR1, which is a type of signaling protein called a receptor tyrosine kinase, is overproduced in some breast tumors, which suggests that it could be a potential target for treatment, the researchers explained. (cancer.gov)
  • kinase( Brk )) is a member of the non- receptor protein- tyrosine kinase family and is expressed in two- thirds of all breast tumors. (wikigenes.org)
  • A genetic mutation in the protein c-kit tyrosine kinase receptor - called a c-kit oncogene - is found in 25 to 30 percent of tumors. (whole-dog-journal.com)
  • Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP + a protein-L-tyrosine = ADP + a protein-L-tyrosine phosphate. (cathdb.info)
  • VEGFR-1 is expressed in two forms, predominantly on endothelial cells, giving rise to a full-length membrane bound receptor and a truncated soluble receptor. (abbiotec.com)
  • Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. (proteopedia.org)
  • Imagine a cell as a flexible bag with the outer surface as the cell membrane containing proteins that act as gate keepers to communicate, or sense, specific conditions outside the cell that in turn trigger a cascade of signaling inside the cell," said Vashisth. (bonesbrigaderecords.com)
  • After electrophoresis, protein were moved onto polyvinylidene fluoride (PVDF) membrane with 0.2 m pore size (EMD Millipore, Billerica, MA, USA). (ecologicalsgardens.com)
  • Rearranged during transfection (RET), kinase alterations, which include fusions and activating point mutation, lead to overactive RET signaling and uncontrolled cell growth. (medscape.com)
  • A third adaptor, Gads, bridges the recruitment of SLP-76 to LAT, and together these adaptors nucleate the formation of large signaling complexes that transmit antigen receptor signals into the cell. (technion.ac.il)
  • We characterized the role of SLP-76 in recruiting and activating specific kinases that regulate antigen receptor responsiveness. (technion.ac.il)
  • Here, TIRF microscopy was used to visualize the antigen receptor-induced co-clustering of Gads and LAT. (technion.ac.il)
  • The p75 receptor has been shown to act as a co-receptor in the presence of high affinity receptors and as an antagonist in their absence. (intechopen.com)
  • One current project involves the targeting of EphB4 receptor tyrosine kinase using an antagonist as a therapeutic strategy. (northwestern.edu)
  • Mechanisms of mitogen-activated protein kinase activation in experimental diabetes'J.Am.Soc.Nephrol. (nii.ac.jp)
  • Expression of mitogen-activated protein kinase family in rat renal development'Kidney Int. 58. (nii.ac.jp)
  • Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase are required for rat renal development'Kidney Int. (印刷中). (nii.ac.jp)
  • The purpose of this study was to explore potential sites for signal integration mediating synergism, focusing on extracellular signal-regulated kinase (ERK) and transcription factors involved in proliferation and inflammation as likely candidates. (ersjournals.com)
  • Shp2 binding to β4 enhances the activation of Src, which, in turn, phosphorylates the multiadaptor Gab1 predominantly on consensus sites for Grb2 association, leading to privileged stimulation of the Ras-extracellular signal-regulated kinase (ERK) cascade. (rupress.org)
  • Non-receptor tyrosine kinases regulate cell growth, proliferation, differentiation, adhesion, migration and apoptosis, and they are critical components in the regulation of the immune system. (wikipedia.org)
  • These results unravel a novel pathway whereby β4 directs tyrosine kinase-based signals toward adhesion-unrelated outcomes. (rupress.org)
  • Tissue culture supernatant is purified by either protein A/G or affinity purification methods. (bdbiosciences.com)
  • Compared to VEGFR-2 the Flt-1 receptor has a higher affinity for VEGF but a weaker signaling activity. (prospecbio.com)
  • The biological functions of sVEGFR-1 still are not clear, but it seems to be an endogenous regulator of angiogenesis, binding VEGF with the same affinity as the full-length receptor. (prospecbio.com)
  • BRK - 2 and BRK - 3, which constitute dual- affinity signaling receptor complexes for BMPs, are co- expressed in condensing precartilaginous cells, while BRK - 1 is weakly expressed in the limb. (wikigenes.org)
  • Interactions indicated with continuous lines are interactions related to methodologies like: two hybrid, protein complementation assay, affinity chromatography technology and similar methodologies that imply a physical interaction. (atlasgeneticsoncology.org)
  • Affinity purification of GPI anchored urokinase type plasminogen activator receptor from chrysotile exposed cells indicated that asbestos altered the profile of proteins and phosphoprotein complexes with this receptor. (cdc.gov)
  • The mutations responsible for piebaldism lead to a nonfunctional KIT protein. (medlineplus.gov)
  • Single mutations of Tyr-749 or Tyr-753 to phenylalanine reduced Nyk kinase activity toward exogenous substrate to 39 or 10% of that of the wild type Nyk, respectively, whereas the Tyr-754 mutant is completely inactive. (elsevier.com)
  • According to new data, DDR2 mutations are present in about 4% of lung squamous cell cancers, and are associated with sensitivity to the tyrosine kinase inhibitor dasatinib ( Sprycel ). (medscape.com)
  • In this study, Dr. Meyerson and colleagues attempted to identify new therapeutic targets by analyzing the tyrosine kinome of squamous cell cancer of the lung for possible kinase mutations. (medscape.com)
  • The role of the oncogenic serine/threonine kinase PIM1 in prostate cancer - PIM1 is coexpressed with c-MYC and dramatically enhances c-MYC-driven prostate tumorigenesis in a kinase-dependent manner. (northwestern.edu)
  • We show that one compound, PP121, blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases. (proteopedia.org)
  • Molecular targets acted on by products in development for blood pressure disorders include angiotensin receptors, tyrosine protein kinases and phosphodiesterases. (openpr.com)
  • This is an exciting opportunity to support some of our preliminary research that showed promise in new protein drug targets involved in several diseases," said Harish Vashisth, associate professor of chemical engineering and recipient of the NIH's Outstanding Investigator award. (bonesbrigaderecords.com)
  • Using the nucleotide-binding sites of proteins TNR kinases specifically at heart as drug-targets, several chemical libraries have already been curated that consist of substances either knownor forecasted and purified to homogeneity [8]. (immune-source.com)
  • Orthologous to human SHC2 (SHC adaptor protein 2). (jax.org)
  • Cbl (Casitas B-lineage Lymphoma) is a receptor tyrosine kinase adaptor protein with E3 ubiquitin ligase activity that regulates receptor and nonreceptor tyrosine kinases, resulting in their down-regulation. (bl.uk)
  • We have also identified novel candidate PIM1-interacting proteins in prostate epithelial cells. (northwestern.edu)
  • The dimerization of c-Src is mediated by the interaction of the myristoylated N-terminal region of one partner and the kinase domain of another partner. (wikipedia.org)
  • the crystal structure of an eph receptor sam domain reveals a mechanism for modular dimerization. (berkeley.edu)
  • Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) belongs to a family of five receptor tyrosine kinase receptors that are specific to a number of angiogenic factors including VEGF and PDGF, and are therefore thought to play a role in the angiogenic process. (abbiotec.com)
  • This article focuses on the use of targeted therapies in cervical cancer, specifically evaluating antiangiogenesis and endothelial growth factor receptor-related treatments. (jnccn.org)
  • Insulin receptor/protein tyrosine kinase (PTK) signaling can cause marked increases in this response. (endotext.org)
  • c-Cbl is a key protein in the alternate pathway of insulin signalling to glucose transporter type 4 (GLUT4) translocation in 3T3-L1 adipocytes. (bl.uk)
  • Drosophila sequences at chromosomal positions 25D( Brk 25D) and 43E( Brk 43E) are similar to the TGF beta type I receptor serine/ threonine kinases and are expressed broadly during embryogenesis. (wikigenes.org)
  • It is a natural taxane, and it prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition. (medscape.com)
  • c-Src should not be confused with CSK (C-terminal Src kinase), an enzyme that phosphorylates c-Src at its C-terminus and provides negative regulation of Src's enzymatic activity. (wikipedia.org)
  • This enzyme is one of three protein components that form the anthrax toxin produced by the bacterium Bacillus anthracis. (alamy.com)
  • Thirty-two non-receptor tyrosine kinases have been identified in human cells (EC (wikipedia.org)
  • Expression of mitogen-activated protein kinases in human renal dysplasia'Kidney Int. 61. (nii.ac.jp)
  • Single-pass transmembrane receptors (SPTMRs) are involved in essential processes of biophysical and pathological nature in the human. (izon.com)
  • Each protein is depicted as circle whose color refers to the human pathology where the interaction with PTP1B is found misregulated. (atlasgeneticsoncology.org)
  • have used HEK293 human embryonic kidney cell line, stimulated with a high EGF concentration and observed that overexpression of PTP1B reduces EGF-dependent ERK activation, by dephosphorylating phospho-tyrosines of the scaffold protein GAB1 . (atlasgeneticsoncology.org)
  • Therefore, TAM receptor activation and regulation can independently influence both oligodendrocyte survival and the microglial response after CNS damage. (edu.au)
  • our data imply that EPHA6 expression is beneficial for glioblastoma multiforme inhibition, particularly in combination with activation of BMP-2 signaling.These results suggest that EPHA6 expression or protein levels could be used as biomarkers for identification of subsets of glioblastoma multiforme patients who might benefit from BMP treatment. (nih.gov)
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)
  • NRF2 activation depends on its dissociation from the repressor protein KEAP1 and its subsequent translocation into the nucleus 2 . (nature.com)
  • By using a vaccinia virus expression system to express a constitutively activated form of Nyk, we identified the major sites of Nyk autophosphorylation in tryptic peptide IY 749 SGDY 753 Sy 754 R. Tyr-749, Tyr-753, and Tyr-754 in this peptide lie in the activation loop of the kinase domain. (elsevier.com)
  • Tyr-749, Tyr-753, and Tyr-754 in this peptide lie in the activation loop of the kinase domain. (elsevier.com)
  • Activation of activator protein‐1 is synergistic, and Rho activation by lysophosphatidic acid is required for synergism in both activator protein‐1 activation and mitogenesis. (ersjournals.com)
  • This activation requires interactions between TMD helices whose role in receptor activation becomes important. (izon.com)
  • High impact information on BRK 1/ HSPC300 Thus, AtSCAR proteins are likely to function in association with At BRK 1, and perhaps other Arabidopsis homologs of WAVE complex components, to regulate activation of the Arp2, 3 complex in vivo. (wikigenes.org)
  • PTK6( also known as Brk ) is a non- receptor protein tyrosine kinase, whose m... with the activation of its kinase activity by calcium/ ionomycin and its influence on K10 expression, all indicate. (wikigenes.org)
  • Furthermore, 17ß-estradiol increased RBP4 mRNA which was attributed to activation of oestrogen receptor alpha (ER-a). (bl.uk)
  • SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. (proteopedia.org)
  • CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. (rndsystems.com)
  • Adding a carrier protein enhances protein stability, increases shelf-life, and allows the recombinant protein to be stored at a more dilute concentration. (rndsystems.com)
  • In general, we advise purchasing the recombinant protein with BSA for use in cell or tissue culture, or as an ELISA standard. (rndsystems.com)
  • Recombinant VEGFR-1 comprises a 298 amino acid fragment (31-328) corresponding to the IgG-like domains 1-3 from the mature soluble VEGFR protein. (abbiotec.com)
  • Predicted to enable transmembrane-ephrin receptor activity. (nih.gov)
  • Predicted to enable receptor tyrosine kinase binding activity. (jax.org)
  • During Drosophila oogenesis, spatially restricted activity of the TORPEDO receptor tyrosine kinase first recruits follicle cells adjacent to the oocyte to a posterior cell fate and then specifies dorsal follicle cells. (elsevier.com)
  • The viral oncogene has an unregulated kinase activity which abrogates the need for cytokines and influences differentiation of haematopoietic progenitor cells. (embl.de)
  • All of the double and triple Tyr-Phe mutants reduced Nyk kinase activity to a level below the background. (elsevier.com)
  • We thought that by blocking the DDR1 tyrosine kinase activity, we could develop a potential treatment for triple-negative breast cancer," said Dr. An. (cancer.gov)
  • CHIR-99021 is a glycogen synthase kinase 3 beta inhibitor that has antiproliferative activity in vitro and in vivo. (dcchemicals.com)
  • Non-receptor tyrosine kinases do not contain only a tyrosine kinase domain, nRTKs also possess domains that mediate protein-protein, protein-lipid, and protein-DNA interactions. (wikipedia.org)
  • Some nRTKs without SH2 and SH3 domains possess some subfamily-specific domains used for protein-protein interactions. (wikipedia.org)
  • Their second research project will take an unconventional approach to target protein-protein interactions in proteins inside the cell, part of the G-protein coupled receptor family, that are important in touch, smell and sight and are implicated in many diseases. (bonesbrigaderecords.com)
  • PTP1B is involved in direct/enzymatic or indirect interactions with several proteins. (atlasgeneticsoncology.org)
  • Interactions are categorized according to OLS ( The Ontology Lookup Service ) and according to evidence collected in the major PPI databases (Protein-Protein Interaction Databases). (atlasgeneticsoncology.org)
  • The authors suggest that asbestos initiates endothelial cell phenotypic change through interactions with urokinase type plasminogen activator receptor containing complexes and that this change is mediated through tyrosine kinase cascades. (cdc.gov)
  • Another Src family member Lyn is involved in signaling mediated by B-cell receptor. (wikipedia.org)
  • Another nRTK, Btk, is also involved in signaling mediated by the B-cell receptor. (wikipedia.org)
  • Interacting selectively and non-covalently with a protein C-terminus, the end of any peptide chain at which the 1-carboxyl function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue. (cathdb.info)
  • This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)
  • This positioning allows the receptor to attach (bind) to other proteins, called ligands, outside the cell and to receive signals that help the cell respond to its environment. (medlineplus.gov)
  • In general, the endothelial cell's fate is determined by the combined effects of a large number of positive and negative signals simultaneously transduced by numerous receptors. (medscape.com)
  • An amino acid that occurs in endogenous proteins. (drugbank.com)
  • 2013) Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. (guidetopharmacology.org)
  • [3] It has 1255 amino acids and is a highly phosphorylated protein. (indianjcancer.com)
  • One of the studies will focus on better understanding the folding and binding mechanisms of novel peptides, a short string of amino acids that are building blocks of proteins and perform biological functions. (bonesbrigaderecords.com)
  • Infection-driven metabolic changes are characterized by an accelerated flux of glucose, lipids, proteins and amino acids that may result in net protein loss and diabetic-like hyperglycemia [ 1 , 2 ]. (biomedcentral.com)
  • The open reading frame includes 1305 bp and codes for a protein of 435 amino acids (Olivier et al. (atlasgeneticsoncology.org)
  • A number of actin-binding proteins, including spectrin, alpha-actinin and fimbrin, contain a 250 amino acid stretch called the actin binding domain (ABD). (embl.de)
  • Proteins containing only a single amino terminal CH domain. (embl.de)
  • Description: A sandwich quantitative ELISA assay kit for detection of Mouse Tubulin Polymerization Promoting Protein (TPPP) in samples from tissue homogenates or other biological fluids. (1elisakits.com)
  • Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). (cathdb.info)
  • BMP proteins are synthesized as large precursor molecules that are cleaved by proteolytic enzymes. (mclab.com)
  • HO-1 protein expression can be induced by ubiquitous stimuli not only cytokines and growth factors but also heme (its substrate) and antioxidant. (hindawi.com)
  • Our selection of a collection was influenced with the recognition the fact that substrate binding storage compartments of inositol phosphate kinases are extremely electropositive buy Protopanaxatriol [7,8,21,22]. (immune-source.com)