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 1.14.16.2.
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 3.1.4.3), 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.
BENZOIC ACID amides.
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]s.edu, 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 ...
IPVIEPSGPELVVKPGETVTLRCVGNGSVEWDGPISPHWTLYSDGPSSVLTTNNATFQNTRTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAKEVVVFEDQDALLPCLLTDPVLEAGVSLVRLRGRPLLRHTNYSFSPWHGFIIHRAKFIQGQDYQCSALMGGRKVMSISIRLKVQKVIPGPPALTLVPAELVRIRGEAAQIVCSASNIDVDFDVFLQHNTTKLAIPQRSDFHDNRYQKVLTLSLGQVDFQHAGNYSCVASNVQGKHSTSMFFRVVESAYLDLSSEQNLIQEVTVGEGLNLKVMVEAYPGLQGFNWTYLGPFSDHQPEPKLANATTKDTYRHTFTLSLPRLKPSEAGRYSFLARNPGGWRALTFELTLRYPPEVSVIWTSINGSGTLLCAASGYPQPNVTWLQCAGHTDRCDEAQVLQVWVDPHPEVLSQEPFQKVTVQSLLTAETLEHNQTYECRAHNSVGSGSWAFIPISAGARTHPPDEFLFTP ...
(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.
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
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 ...
... in tyrosine-protein kinase receptors; and in the programmed cell death protein 1 (PD1). Immunoglobulin V-set, subgroup InterPro ... V-set domains are found in diverse protein families, including immunoglobulin light and heavy chains; in several T-cell ... receptors such as CD2 (Cluster of Differentiation 2), CD4, CD80, and CD86; in myelin membrane adhesion molecules; in junctional ...
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 ...
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 ...
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". ...
"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 ... Clustered Pcdhs proteins are detected throughout the neuronal soma, dendrites and axons and are observed in synapses and growth ... Schreiner and Weiner showed that Pcdhα and γ proteins can form multimeric complexes. If all three classes of Pcdhs could engage ...
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 ...
Nusse R, Xu YK (1998). "The Frizzled CRD domain is conserved in diverse proteins including several receptor tyrosine kinases". ... Frizzled proteins include cysteine-rich domain that is conserved in diverse proteins, including several receptor tyrosine ... Frizzled is a family of G protein-coupled receptor proteins[2] that serves as receptors in the Wnt signaling pathway and other ... include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal-specific kinase (NSK2), and ROR1 and ROR2. The ...
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 ...
"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 ...
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 Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome. Molecular cell, 65(2), 347-360. [13] Xiong, ... Role of Mammalian Vacuolar Protein-sorting Proteins in Endocytic Trafficking of a Non-ubiquitinated G Protein-coupled Receptor ... There are many predicted phosphorylation sites in the non-transmembrane regions with various protein kinases including AGC, ... Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Nat Commun 10, 2055 ( ...
"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- ...
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have ... the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor ... 1995). "cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases". Oncogene. 10 (5): 897- ... Ciossek T, Ullrich A (1997). "Identification of Elf-1 and B61 as high affinity ligands for the receptor tyrosine kinase MDK1". ...
Eph receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinases (RTKs). Since ephrin ligands ( ... a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases". Cell. 82 (3): 359-370. doi:10.1016/0092-8674(95) ... Ephrins (also known as ephrin ligands or Eph family receptor interacting proteins) are a family of proteins that serve as the ... The ephrin protein family of class A and class B guides ligands with the EphB family cell-surface receptors to provide a steady ...
"The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". The Journal of Biological ... "Fyn kinase-directed activation of SH2 domain-containing protein-tyrosine phosphatase SHP-2 by Gi protein-coupled receptors in ... "SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1". The Journal of Biological ... nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases ...
All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein ... Sato, A; Iwama A; Takakura N; Nishio H; Yancopoulos G D; Suda T (Aug 1998). "Characterization of TEK receptor tyrosine kinase ... Sato A, Iwama A, Takakura N (1998). "Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human ... ligands for the endothelial-specific receptor tyrosine kinase Tie2". J. Biol. Chem. 273 (29): 18514-21. doi:10.1074/jbc.273.29. ...
The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases. EPH receptors typically ... a new member of the EPLG gene family encoding ligands of EPH-related protein-tyrosine kinase receptors". Genomics. 41 (1): 17- ... 1996). "Elk-L3, a novel transmembrane ligand for the Eph family of receptor tyrosine kinases, expressed in embryonic floor ... as opposed to the cell with the receptor. Upon receptor-ligand interaction the tyrosine residues become phosphorylated and ...
1997). "A family of proteins that inhibit signalling through tyrosine kinase receptors". Nature. 386 (6621): 181-6. Bibcode: ... are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase- ... Signal-regulatory protein gamma is a protein that in humans is encoded by the SIRPG gene. SIRPG has also recently been ... The protein encoded by this gene is a member of the signal-regulatory protein (SIRP) family, and also belongs to the ...
Proto-oncogene tyrosine-protein kinase Yes is a non-receptor tyrosine kinase that in humans is encoded by the YES1 gene. This ... Non-receptor type protein-tyrosine kinases closely related to src and yes compose a multigene family". Int. Symp. Princess ... "Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family ... "Autophosphorylation activity and association with Src family kinase of Sky receptor tyrosine kinase". Biochem. Biophys. Res. ...
"In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation". ... Fc fragment of IgG receptor IIb (coded by FCGR2B gene) is a low affinity inhibitory receptor for the Fc region of ... Inhibition of the MAP kinase pathway, together with the anti-apoptotic kinase Akt can negatively affect proliferation and ... allows fast internalization of the receptor in myeloid cells. Both forms contain the Immunoreceptor Tyrosine-based Inhibitory ...
Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 ( ... Roskoski (2005-12-23). "Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor". Biochemical ... Altered forms of this receptor may be associated with some types of cancer. KIT is a receptor tyrosine kinase type III, which ... receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein". ...
Examples of membrane receptors include G Protein-Coupled Receptors and Receptor Tyrosine Kinases. Intracellular receptors are ... Examples of membrane receptors include G Protein-Coupled Receptors and Receptor Tyrosine Kinases. Intracellular receptors are ... Examples of membrane receptors include G Protein-Coupled Receptors and Receptor Tyrosine Kinases. Intracellular receptors are ... By looking at three major types of receptors, (G protein coupled receptors, receptor tyrosine kinases, and ion channel ...
"Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP". The Journal of ... "Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP". The Journal of ... This gene encodes a protein which contains a C-terminal domain able to interact with the angiotensin II receptor type 2 (AT2) ... receptor-interacting proteins, in health and disease, with special emphasis on its role in carcinogenesis". Gene. 626: 54-63. ...
1996). "In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcgammaRII) phosphorylation ... "Fc gamma receptors differ in their structural requirements for interaction with the tyrosine kinase Syk in the initial steps of ... Low affinity immunoglobulin gamma Fc region receptor II-a is a protein that in humans is encoded by the FCGR2A gene. FCGR2A has ... 1997). "Influence of tyrosine phosphorylation on protein interaction with FcgammaRIIa". Biochim. Biophys. Acta. 1357 (3): 348- ...
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ... The CD20 proteins are sticking out of the cell membrane, and rituximab, the Y-shaped antibody, is binding to the CD20 proteins. ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... In contrast, when the B cell lacked this asymmetric protein cluster, it was killed only 40% of the time.[36][37] ...
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 ... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive ...
Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ... Fig 2. Schematic diagram of a GABAA receptor protein ((α1)2(β2)2(γ2)) which illustrates the five combined subunits that form ... The GABAA receptors are made up of subunits which form a receptor complex. Humans have 19 receptor subunits and are classified ... The synaptic anchoring protein Gephyrin is indirectly linked to the GABAA receptors. ...
... binding to cAMP-dependent protein kinase (PKA).[111] Moclobemide is chemically unrelated to irreversible MAOI antidepressants ... See also: Receptor/signaling modulators • Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake ... Substrates→Products: Phenylalanine→Tyrosine. *Inhibitors: 3,4-Dihydroxystyrene. TH. *Substrates→Products: Tyrosine→L-DOPA ( ... The elimination half-life is around 2 hours.[8][118] It is moderately bound to plasma proteins, especially albumin.[8] However ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... For example, strychnine acts as an allosteric inhibitor of the glycine receptor in the mammalian spinal cord and brain stem. ... The active site is a region on an enzyme which a particular protein or substrate can bind to. The active site will only allow ... Strychnine binds to an alternate site that reduces the affinity of the glycine receptor for glycine, resulting in convulsions ...
"Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired ... Complement receptor deficiency. *v. *t. *e. Genetic disorder, protein biosynthesis: Transcription factor/coregulator ...
1992). "The lymphocyte-specific tyrosine protein kinase p56lck is endocytosed in Jurkat cells stimulated via CD2.". J. Immunol. ... Tamén recibiu o nome de antíxeno de superficie de células T T11/Leu-5, LFA-2, receptor LFA-3, receptor de eritrocitos e ... to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation pathways dependent on protein kinase C and ... Wilkins A, Yang W, Yang J (2003). "Structural biology of the cell adhesion protein CD2: from molecular recognition to protein ...
... who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, ... Serine/threonine/tyrosine phosphorylation[edit]. Addition of a negatively charged phosphate group can lead to major changes in ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... The nociceptin/nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol.[110] ...
Type 3: Kinase-linked and related receptors (see "Receptor tyrosine kinase" and "Enzyme-linked receptor") - They are composed ... G protein-coupled receptors (metabotropic receptors) - This is the largest family of receptors and includes the receptors for ... GABA receptors: GABA-A, GABA-C. GABA. Cl− , HCO−3 [11]. Glutamate receptors: NMDA receptor, AMPA receptor, and Kainate receptor ... receptors, G protein-linked (metabotropic) hormone receptors, and enzyme-linked hormone receptors.[1] Intracellular receptors ...
positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... receptor binding. • neurotrophin TRKB receptor binding. • growth factor activity. • GO:0001948 protein binding. ... positive regulation of receptor binding. • regulation of protein localization to cell surface. • regulation of receptor ...
EGFR-specific tyrosine kinase inhibitors such as gefitinib have shown limited therapeutic success. This resistance is proposed ... Upon activation, "low-affinity" IL-2 receptors are replaced by "high-affinity" IL-2 receptors consisting of α, β, and γ chains ... the Wnt signaling pathway leads to stabilization of β-catenin through inactivation of a protein complex containing the tumor ... HER2 kinase inhibitors, such as lapatinib, have also demonstrated clinical efficacy in HER2 overexpressing breast cancers by ...
FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a ... Thakker DR, Standifer KM (2003). „Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation.". ... Nociceptinski receptor (NOP, orfaninski FQ receptor, kapa tip 3 opioidni receptor) je protein koji je kod čoveka kodiran OPRL1 ... opioidnom receptoru sličan 1) genom.[1] Nociceptinski receptor je G protein-spregnuti receptor čiji prirodni ligand je poznat ...
"Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3". ... Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker. ... This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, ...
2000). "The protein tyrosine kinase family of the human genome". Oncogene 19 (49): 5548-5557. PMID 11114734. doi:10.1038/sj.onc ... Zwick, E. Bange, J. Ullrich, A. (2001). "Receptor tyrosine kinase signalling as a target for cancer intervention strategies". ... G protein-spregnuti receptor (Hedgehog, Wnt) • RTK (TGF beta, MAPK/ERK) • Notch • JAK-STAT • Akt/PKB • Fas apoptoza • Hippo • ... OPM protein 2k1k Receptor tirozinske kinaze (RTK) su receptori ćelijske površine visokog-afiniteta za mnoge polipeptidne ...
The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... receptor tyrosine kinases". EMBO J. 15 (2): 290-298. doi:10.1002/j.1460-2075.1996.tb00359.x. PMC 449944. PMID 8617204.. ...
Receptor protein serine/threonine kinase (EC 2.7.11.30). *Bone morphogenetic protein receptors *BMPR1 ... tyrosine 3-monooxygenase) kinase (EC 2.7.11.6). *STK4. Myosin-heavy-chain kinase (EC 2.7.11.7). *Aurora kinase *Aurora A kinase ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene ...
... and the Fyn protein-tyrosine kinase". Molecular Biology Reports. 26 (3): 173-7. doi:10.1023/A:1006954206151. PMID 10532312.. ... "Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living ... protein binding. • identical protein binding. • actin binding. • protein kinase binding. • small GTPase binding. • Rac GTPase ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ...
positive regulation of protein tyrosine kinase activity. • positive regulation of protein targeting to membrane. • modulation ... type 5 metabotropic glutamate receptor binding. • type 8 metabotropic glutamate receptor binding. • signaling receptor activity ... negative regulation of protein processing. • protein destabilization. • activation of protein kinase activity. • calcium- ... ATP-dependent protein binding. • metal ion binding. • tubulin binding. • protein binding. • identical protein binding. • copper ...
protein tyrosine kinase binding. Cellular component. • cytoplasm. • cell junction. • cytoskeleton. • focal adhesion. • cell ... a CD36 receptor agonist) versus thrombin treatment, which may implicate CASS4 mediated signaling in platelet hyperreactivity.[ ... positive regulation of protein tyrosine kinase activity. • positive regulation of substrate adhesion-dependent cell spreading. ... "Entrez Gene: Cas scaffolding protein family member 4".. *^ a b Tikhmyanova N, Little JL, Golemis EA (April 2010). "CAS proteins ...
CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ... UMich Orientation of Proteins in Membranes protein/pdbid-2hac - Zeta-zeta dimer of T cell receptor ... This allows cytoplasmic kinases of the Syk family (ZAP-70) to bind to the ITAM and activated ZAP-70 phosphorylates tyrosines on ... Zap70 - a Syk family kinase that binds to ITAM sequences upon tyrosine phosphorylation by Lck and Fyn, and phosphorylates LAT ...
cellular protein metabolic process. • insulin receptor signaling pathway. • positive regulation of protein kinase B signaling. ... positive regulation of insulin receptor signaling pathway. • positive regulation of peptidyl-tyrosine phosphorylation. • ... protein serine/threonine kinase activator activity. • receptor ligand activity. Cellular component. • extracellular region. • ... positive regulation of protein serine/threonine kinase activity. • carbohydrate metabolic process. • regulation of receptor ...
... it reduces neuron firing rate and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT ... Receptors. Varies greatly across species;. Human receptors: hTAAR1[2] and hTAAR2[2]. ... It is possible to assemble phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines, tyrosine and ... Phenethylamine has been shown to bind to two human trace amine-associated receptors, hTAAR1 and hTAAR2, as an agonist.[2] ...
In terms of intracellular signaling, GHB inhibits mitogen activated protein (MAP) kinase action via the GABAB receptor ... Tyrosine→Melanin. *Albinism: Ocular albinism (1). *Oculocutaneous albinism (Hermansky-Pudlak syndrome). *Waardenburg syndrome ... Ren, X.; Mody, I. (2003). "Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABAB receptor ... GABAA and GABAC and the G-protein couple receptors GABAB. The GABAB receptor has been found to be the most important of the ...
positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... positive regulation of receptor binding. • regulation of protein localization to cell surface. • regulation of receptor ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ...
Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... FMS-like tyrosine kinase 3 ligand (FLT3L). *Leukemia/leukocyte inhibitory factor (LIF) ... Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte.[1] They are protein ...
Tyrosine kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Dacomitinib ... 2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et Biophysica Acta (BBA ... See also: Discovery and development of Bcr-Abl tyrosine kinase inhibitors. Nilotinib was developed by Novartis.[3] It was ... Structurally related to imatinib,[18] It is 10-30 fold more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity ...
Dan R Robinson, Yi-Mi Wu ja Su-Fang Lin, The protein tyrosine kinase family of the human genome, 20 November 2000, Volume 19, ... Beyond receptor ligands". Cancer Science 99 (2): 214-20. PMID 18271917. doi:10.1111/j.1349-7006.2007.00676.x. Cite uses ... "Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification". FASEB J. ... "Peptide inhibitors of protein kinases-discovery, characterisation and use". Biochimica et Biophysica Acta (BBA) - Proteins and ...
The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor.[7] Upon ligand binding, the receptor undergoes ... and subsequent activation of protein kinase A. ACTH influences steroid hormone secretion by both rapid short-term mechanisms ... Postorgasmic illness syndrome (POIS), through production of tyrosine hydroxylase and dopamine β-hydroxylase, which two enzymes ... A family of related receptors mediates the actions of these hormones, the MCR, or melanocortin receptor family. These are ...
... the depth of complexity and compound mutations present in amplified therapeutic targets such as receptor tyrosine kinase genes ... October 2017). "Multiplexed quantification of proteins and transcripts in single cells". Nature Biotechnology. 35 (10): 936-939 ... In 2017, two approaches were introduced to simultaneously measure single-cell mRNA and protein expression through ...
... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ... positive regulation of tyrosine phosphorylation of STAT protein. • regulation of receptor activity. • interleukin-15-mediated ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ... The β chain of IL-15R recruits and also activates protein tyrosine kinases of the Src family including Lck, Fyn and Lyn kinase ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... GO:0004672 protein kinase activity GO:0004713 protein tyrosine kinase activity GO:0005515 protein binding GO:0005524 ATP ...
Met receptor tyrosine kinase: enhanced signaling through adapter proteins.. Furge KA1, Zhang YW, Vande Woude GF. ... The Met receptor tyrosine kinase is the prototypic member of a small subfamily of growth factor receptors that when activated ... and the large adapter protein Gab1. These adapter proteins in turn recruit several signal transducing proteins to form an ... Analysis of how these adapter proteins bind to the Met receptor and what signal transducers they recruit have led to more ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Tyrosine protein kinase, EGF/ERB/XmrK receptor (IPR016245). Short name: Tyr_kinase_EGF/ERB/XmrK_rcpt ... GO:0006468 protein phosphorylation GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway ...
View protein in PROSITE. PS00107, PROTEIN_KINASE_ATP, 1 hit. PS50011, PROTEIN_KINASE_DOM, 1 hit. PS00109, PROTEIN_KINASE_ ... View protein in PROSITE. PS00107, PROTEIN_KINASE_ATP, 1 hit. PS50011, PROTEIN_KINASE_DOM, 1 hit. PS00109, PROTEIN_KINASE_ ... Receptor protein-tyrosine kinaseSequence analysis. Automatic assertion according to sequence analysisi ... Receptor protein-tyrosine kinaseARBA annotation. Automatic assertion according to rulesi ...
Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs.. Hines J1, Gough JD, ... Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proc Natl Acad Sci U S ... Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proc Natl Acad Sci U S ... Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. Proc Natl Acad Sci U S ...
Eph receptor inhibitor ALW-II-41-27 is a novel Eph receptor tyrosine kinase inhibitor. ... High Purity Kinase Inhibitors on Signaling Pathways. Trusted by 10,000+ Scientists since 2006 Search. ...
View protein in PROSITE. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 hit. ... View protein in PROSITE. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 hit. ... View protein in InterPro. IPR030118 FLT3. IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR001245 Ser-Thr/Tyr_kinase ... View protein in InterPro. IPR030118 FLT3. IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR001245 Ser-Thr/Tyr_kinase ...
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ... ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProt ... Protein Feature View of PDB entries mapped to a UniProtKB sequence * Number of PDB entries for B4DHN3: no matching PDB entries ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ... ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein] UniProt ... This protein in other organisms (by gene name): P04626 - Homo sapiens 33 * B2RZG3 - Homo sapiens no matching PDB entries ...
Receptor tyrosine-protein kinase erbB-2. Details. Name. Receptor tyrosine-protein kinase erbB-2. Kind. protein. Organism. Human ... Receptor tyrosine-protein kinase erbB-2. P04626. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. ...
Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within ... The mechanisms by which most receptor protein-tyrosine kinases (RTKs) transmit signals are now well established. ... the cytoplasmic domains of the receptors. This tidy picture … ... Receptor Protein-Tyrosine Kinases / genetics * Receptor Protein ... Deceiving appearances: signaling by "dead" and "fractured" receptor protein-tyrosine kinases Bioessays. 2001 Jan;23(1):69-76. ...
... study to inhibit the subsequent ability of insulin to stimulate the tyrosine phosphorylation of an expressed insulin receptor ... Activation of the endogenous protein kinase Cs in human kidney fibroblast (293) cells was found in the present ... Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612 Biochemistry. 1997 Oct ... However, unlike the wild-type protein, activation of protein kinase C did not inhibit the insulin-stimulated tyrosine ...
Systematic reviews of Receptor tyrosine-protein kinase erbB-2. Receptor tyrosine-protein kinase erbB-2 in N Eng J Med, Lancet, ... Chemical Information on Receptor tyrosine-protein kinase erbB-2. Protein Structural Information on Receptor tyrosine-protein ... on Receptor tyrosine-protein kinase erbB-2. Online Mendelian Inheritence in Man (OMIM) on Receptor tyrosine-protein kinase erbB ... ChemSpider on Receptor tyrosine-protein kinase erbB-2. CTD (Comparative Toxicogenomics Database) on Receptor tyrosine-protein ...
Antibodies for proteins involved in non-receptor tyrosine protein kinase pathways, according to their Panther/Gene Ontology ... Antibodies for proteins involved in non-receptor tyrosine protein kinase pathways; according to their Panther/Gene Ontology ...
... the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. ... the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor ... the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor ... the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor ...
"Receptor Protein-Tyrosine Kinases" by people in this website by year, and whether "Receptor Protein-Tyrosine Kinases" was a ... Receptor Protein-Tyrosine Kinases*Receptor Protein-Tyrosine Kinases. *Kinases, Receptor Protein-Tyrosine ... Tyrosine Kinase Receptors. *Protein-Tyrosine Kinase Receptor. *Receptor, Protein-Tyrosine Kinase. *Receptors, Protein-Tyrosine ... "Receptor Protein-Tyrosine Kinases" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ...
Tyrosine-protein kinase receptor FLT4 explanation free. What is Tyrosine-protein kinase receptor FLT4? Meaning of Tyrosine- ... protein kinase receptor FLT4 medical term. What does Tyrosine-protein kinase receptor FLT4 mean? ... Looking for online definition of Tyrosine-protein kinase receptor FLT4 in the Medical Dictionary? ... Tyrosine-protein kinase receptor FLT4 , definition of Tyrosine-protein kinase receptor FLT4 by Medical dictionary https:// ...
Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2.. [ ... The Tie1 receptor tyrosine kinase was isolated over a decade ago, but so far no ligand has been found to activate this receptor ... Here, we have examined the potential of angiopoietins, ligands for the related Tie2 receptor, to mediate Tie1 activation. We ... In conclusion, we show that Tie1 phosphorylation is induced by multiple angiopoietin proteins and that the activation is ...
Research Report on United States Tyrosine Protein Kinase Receptor Market Report 2017. The Report includes market price, demand ... Figure Merck Tyrosine Protein Kinase Receptor Sales Growth Rate (2012-2017). Figure Merck Tyrosine Protein Kinase Receptor ... Figure Product Picture of Tyrosine Protein Kinase Receptor. Figure United States Tyrosine Protein Kinase Receptor Market Size ( ... Figure Manufacturing Process Analysis of Tyrosine Protein Kinase Receptor. Figure Tyrosine Protein Kinase Receptor Industrial ...
Different Protein Tyrosine Kinases Are Required for B Cell Antigen Receptor-mediated Activation of Extracellular Signal- ... Different Protein Tyrosine Kinases Are Required for B Cell Antigen Receptor-mediated Activation of Extracellular Signal- ... Regulated kinase, c-Jun NH2-terminal Kinase 1, and p38 Mitogen-activated Protein Kinase Aimin Jiang, Andrew Craxton, Tomohiro ... Regulated kinase, c-Jun NH2-terminal Kinase 1, and p38 Mitogen-activated Protein Kinase ...
Antiproliferative Activity of the RAD51 Inhibitor IBR2 with Inhibitors of Receptor Tyrosine Kinases and Microtubule Protein. ... Antiproliferative Activity of the RAD51 Inhibitor IBR2 with Inhibitors of Receptor Tyrosine Kinases and Microtubule Protein ...
G Protein-Coupled Receptor Kinase-5 Attenuates Atherosclerosis by Regulating Receptor Tyrosine Kinases and 7-Transmembrane ... G Protein-Coupled Receptor Kinase-5 Attenuates Atherosclerosis by Regulating Receptor Tyrosine Kinases and 7-Transmembrane ... G Protein-Coupled Receptor Kinase-5 Attenuates Atherosclerosis by Regulating Receptor Tyrosine Kinases and 7-Transmembrane ... G Protein-Coupled Receptor Kinase-5 Attenuates Atherosclerosis by Regulating Receptor Tyrosine Kinases and 7-Transmembrane ...
The Macrophage-Stimulating Protein receptor aka. MSP-R or RON belongs to the c-MET family of receptor tyrosine kinases. The ... Therapeutic implications of an antibody to the human macrophage-stimulating protein receptor tyrosine kinase (RON). Daniel S. ... Therapeutic implications of an antibody to the human macrophage-stimulating protein receptor tyrosine kinase (RON) ... Therapeutic implications of an antibody to the human macrophage-stimulating protein receptor tyrosine kinase (RON) ...
Pillars Article: The CD4 Receptor Is Complexed in Detergent Lysates to a Protein-Tyrosine Kinase (Pp58) from Human T ... Pillars Article: The CD4 Receptor Is Complexed in Detergent Lysates to a Protein-Tyrosine Kinase (Pp58) from Human T ... Pillars Article: The CD4 Receptor Is Complexed in Detergent Lysates to a Protein-Tyrosine Kinase (Pp58) from Human T ... Pillars Article: The CD4 Receptor Is Complexed in Detergent Lysates to a Protein-Tyrosine Kinase (Pp58) from Human T ...
Subunit Structure, Autophosphorylation, and Tyrosine-Specific Protein Kinase Activity of Hepatic Insulin Receptors in Fetal, ... Subunit Structure, Autophosphorylation, and Tyrosine-Specific Protein Kinase Activity of Hepatic Insulin Receptors in Fetal, ... Subunit Structure, Autophosphorylation, and Tyrosine-Specific Protein Kinase Activity of Hepatic Insulin Receptors in Fetal, ... Subunit Structure, Autophosphorylation, and Tyrosine-Specific Protein Kinase Activity of Hepatic Insulin Receptors in Fetal, ...
... with 101 pages available at USD 3500 for single User PDF at ... Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor ... Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor ... Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor ...
A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm ... A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm ... We have identified a receptor protein tyrosine kinase, Sek, that has high relative levels of expression in rhombomeres 3 and 5 ... A receptor protein tyrosine kinase implicated in the segmental patterning of the hindbrain and mesoderm ...
Inhibition of tyrosine protein kinase receptor TIE-2 with 1 mM ATP and biotinylated lck peptide. ...
AlphaLISA no-wash assay kit for detection and quantitation of Human epidermal growth factor receptor 2 (ErbB-2, NEU, or HER2) ... Receptor Tyrosine-Protein Kinase ERbB-2 (HER2) AlphaLISA Detection Kit, 5,000 Assay Points ... is a type I membrane glycoprotein that is a member of the ERBB family of tyrosine kinase receptors. It serves as a receptor for ... It is an orphan receptor with no known ligand, as it acts as a heterodimer with other members of the EGF receptors family. HER2 ...
  • Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. (ebi.ac.uk)
  • Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. (ebi.ac.uk)
  • Src kinase regulation by phosphorylation and dephosphorylation. (ebi.ac.uk)
  • We generated two phosphoPROTACs that couple the tyrosine phosphorylation sequences of either the nerve growth factor receptor, TrkA (tropomyosin receptor kinase A), or the neuregulin receptor, ErbB3 (erythroblastosis oncogene B3), with a peptide ligand for the E3 ubiquitin ligase von Hippel Lindau protein. (nih.gov)
  • These phosphoPROTACs recruit either the neurotrophic signaling effector fibroblast growth factor receptor substrate 2α or the survival-promoting phosphatidylinositol-3-kinase, respectively, to be ubiquitinated and degraded upon activation of specific receptor tyrosine kinases and phosphorylation of the phosphoPROTACs. (nih.gov)
  • In addition, we show that activation of phosphoPROTACs is entirely dependent on their kinase-mediated phosphorylation, as phenylalanine-containing null variants are inactive. (nih.gov)
  • Activation of the endogenous protein kinase Cs in human kidney fibroblast (293) cells was found in the present study to inhibit the subsequent ability of insulin to stimulate the tyrosine phosphorylation of an expressed insulin receptor substrate-1. (nih.gov)
  • This inhibition was also observed in an in vitro phosphorylation reaction if the insulin receptor and its substrate were both isolated from cells in which the protein kinase C had been activated. (nih.gov)
  • To test whether serine phosphorylation of the insulin receptor substrate-1 was contributing to this process, serine 612 of this molecule was changed to an alanine. (nih.gov)
  • The insulin-stimulated tyrosine phosphorylation and the associated phosphatidylinositol 3-kinase activity of the expressed mutant were found to be comparable to those of the expressed wild-type substrate. (nih.gov)
  • However, unlike the wild-type protein, activation of protein kinase C did not inhibit the insulin-stimulated tyrosine phosphorylation of the S612A mutant nor its subsequent association with phosphatidylinositol 3-kinase. (nih.gov)
  • We show that a soluble Ang1 chimeric protein, COMP-Ang1, stimulates Tie1 phosphorylation in endothelial cells with similar kinetics and angiopoietin dose dependence when compared with Tie2. (sigmaaldrich.com)
  • When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner. (sigmaaldrich.com)
  • In conclusion, we show that Tie1 phosphorylation is induced by multiple angiopoietin proteins and that the activation is amplified via Tie2. (sigmaaldrich.com)
  • and the colony-stimulating factor-1 receptor (CSF-1R) in macrophages, by reducing CSF-1-induced tyrosyl phosphorylation. (ahajournals.org)
  • It antagonized MSP-induced phosphorylation of RON, mitogen-activated protein kinase (MAPK), and AKT in several cancer cell lines. (aacrjournals.org)
  • The ability of the tyrphostins to inhibit the EGFRK activity in cardiac membranes was determined by monitoring tyrosine phosphorylation of either the 170 kDa protein or immunoprecipitated EGF receptor at 0° and room temperature, respectively. (amrita.edu)
  • A polymer, the tails of the intracellular domains of the two receptors are in contact with one another, activating the function of their protein kinases, Phosphorylation results in the assembly of the tail of the receptor's intracellular domain into a signaling complex. (creativebiomart.net)
  • The newly phosphorylated tyrosine site immediately becomes the binding site for intracellular signaling proteins, and there may be 10 to 20 different intracellular signaling proteins that are activated after binding to the receptor phosphorylation site. (creativebiomart.net)
  • Phosphorylation of specific tyrosine residues within an activating receptor provides a binding site for proteins containing the SH2 domain and the phosphotyrosine binding (PTB) domain. (creativebiomart.net)
  • Phosphorylation and activation of these two proteins that bind to the receptor triggers a signal transduction pathway. (creativebiomart.net)
  • Syk-deficient cells abolished the tyrosine phosphorylation phospholipase C (PLC) -gamma, resulting in no inositol, 1,4,5-tris … More phosphate (IP3) generation, as well as calcium moblization upon receptor stimulation. (nii.ac.jp)
  • Publications] Shimomura,R.: 'Phosphorylation sites of myelin basic protein by a catalytic fragment of non-receptor type protein-tyrosine kinase p72syk and comparison with those by insulin receptor kinase. (nii.ac.jp)
  • We found that FcR engagement by immune complexes induced the phosphorylation of Syk, a protein tyrosine kinase acting immediately downstream of FcRs. (pasteur.fr)
  • Therefore, protein tyrosine phosphorylation by Syk represents a novel pathway for the induction of DC maturation. (pasteur.fr)
  • Protein kinase C activation induces tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDA receptor. (ox.ac.uk)
  • The aim of this study was to test whether this effect could be mediated by direct tyrosine phosphorylation of the NR2A or NR2B subunits of the receptor. (ox.ac.uk)
  • An increase in tyrosine phosphorylation of both NR2A (76 +/- 11% above control) and NR2B (41 +/- 11%) was observed. (ox.ac.uk)
  • PMA treatment also produced an increase in the phosphorylation of serine 890 on the NR1 subunit, a known PKC site, at 5 min with phosphorylation returning to near basal levels by 10 min while tyrosine phosphorylation of NR2A and NR2B was sustained for up to 15 min. (ox.ac.uk)
  • These results suggest that the modulation of NMDA receptor function seen with PKC activation may be the result of tyrosine phosphorylation of NR2A and/or NR2B. (ox.ac.uk)
  • Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. (nih.gov)
  • May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. (nih.gov)
  • Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation. (wikipedia.org)
  • In summary, this is the first statement demonstrating that AZD1208 inhibits growth of liposarcoma cells and that this activity is usually mediated through Pim-3 kinase, STAT-3, mTOR, S6 and AMPK expression and ACY-241 phosphorylation pathways. (biogeology.org)
  • AZD1208 Reduces Phosphorylation of STAT-3 in 93T449 Individual Liposarcoma Cells and Pharmacological Inhibition of STAT-3 Network marketing leads to Reduced amount of the Cell Success Evidence suggests a job of STAT-3 proteins phosphorylation/activation in cancers cell success [29]. (biogeology.org)
  • We hence searched for to explore whether STAT-3 is normally portrayed and phosphorylated in 93T449 cells and whether AZD1208 modulates STAT-3 proteins appearance and phosphorylation in the cells. (biogeology.org)
  • Nevertheless, treatment with AZD1208 significantly decreased phosphorylation of STAT-3 without impacting its total proteins appearance in 93T449 cells. (biogeology.org)
  • The activation of signal transduction through the FcγRI receptor, as measured by the respiratory burst, is associated with the tyrosine phosphorylation and catalytic activation of the syk kinase. (elsevier.com)
  • The present invention provides methods for use of IL-21 in combination with a tyrosine kinase inhibitor (TKI) in treatment of diseases in which inhibition of phosphorylation via TK inhibition and modulation of immune function play a clinically beneficial role. (freepatentsonline.com)
  • We focus here on the content and diversity of protein kinases present in worms, together with an assessment of other classes of proteins that regulate protein phosphorylation. (pnas.org)
  • Finally, the richness of phosphorylation-dependent signaling pathways in worms is further supported with the identification of 185 protein phosphatases and 128 phosphoprotein-binding domains (SH2, PTB, STYX, SBF, 14-3-3, FHA, and WW) in the worm genome. (pnas.org)
  • Reversible protein phosphorylation plays a central role in regulating basic functions of all eukaryotes such as DNA replication, cell cycle control, gene transcription, protein translation, and energy metabolism. (pnas.org)
  • Protein phosphorylation is also required for more advanced functions in higher eukaryotes such as cell, organ, and limb differentiation, cell survival, synaptic transmission, cell-substratum and cell-cell communication, and to mediate complex interactions with the external environment. (pnas.org)
  • Because aberrant protein phosphorylation is commonly the cause of cancer and other human diseases, a comprehensive knowledge of the key enzymes that regulate these functions can provide the basis for novel therapeutic intervention strategies. (pnas.org)
  • Here, we present a comparative analysis of the enzymes and adaptor molecules that are the key components of the protein phosphorylation signaling network present in C. elegans . (pnas.org)
  • Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1 /ERK2 and MAPK3 /ERK1. (rcsb.org)
  • We show that Jaks are activated by tyrosine phosphorylation in cells that are briefly exposed to the PTP inhibitor pervanadate (PV), resulting in tyrosine phosphorylation and functional activation of Stat6 (in addition to other Stats). (monash.edu)
  • 2003) and that the overexpression of Gia2 enhances the stimulation of p42/p44 MAPK by PDGF, associated with a PDGFb receptor kinase-catalyzed tyrosine phosphorylation of Gia2 (Alderton et al. (strath.ac.uk)
  • 2001). The tyrosine phosphorylation of endogenous Gia2 might prevent reformation of the inactive Gabg complex, thereby prolonging the lifetime of active G-protein subunits, including Gbg. (strath.ac.uk)
  • The integrative signal mechanism is distinct from the transactivation of RTK by GPCR agonists, which involves stimulation of the tyrosine phosphorylation of the RTK. (strath.ac.uk)
  • The mechanisms by which most receptor protein-tyrosine kinases (RTKs) transmit signals are now well established. (nih.gov)
  • Cases have now been identified in which RTKs lack kinase activity, but, despite being "dead" appear to have roles in signal transduction. (nih.gov)
  • Even stranger are the cases in which genes encoding RTKs produce protein products consisting of only a portion of the kinase domain. (nih.gov)
  • Eph-related receptor tyrosine kinases (RTKs) have been implicated in intercellular communication during embryonic development. (pnas.org)
  • We could demonstrate that the carboxyl termini of the Eph-related RTKs EphA7, EphB2, EphB3, EphB5, and EphB6 interact with the PDZ domain of the ras-binding protein AF6. (pnas.org)
  • Our observations add the PDZ domain to the group of conserved protein modules such as Src-homology-2 (SH2) and phosphotyrosine-binding (PTB) domains that regulate signal transduction through their ability to mediate the interaction with RTKs. (pnas.org)
  • The effects of many growth factors and cytokines are mediated by high-affinity binding to receptor tyrosine kinases (RTKs) resulting in autophosphorylation of the cytoplasmic domain ( 1 ). (pnas.org)
  • Modular structures involved in binding of activated RTKs identified so far include Src-homology-2 (SH2) and phosphotyrosine-binding (PTB) domains, which both bind specifically to phosphorylated tyrosine residues in a sequence-specific fashion ( 2 ). (pnas.org)
  • In an attempt to identify yet-unknown proteins capable of interacting with Eph-related RTKs, we performed two-hybrid screenings. (pnas.org)
  • G protein-coupled receptors (GPCRs) can utilize receptor tyrosine kinases (RTKs) to mediate important cellular responses such as proliferation, differentiation and survival. (eurekaselect.com)
  • Depending on the receptor and cell type, GPCR signaling involves activation of several different RTKs. (eurekaselect.com)
  • RTK BRET-2 assays monitor, in living cells, the specific interaction between RTKs and their effector proteins, which control the activation of specific downstream signaling pathways. (aspetjournals.org)
  • A total of 22 BRET assays have been established for nine RTKs derived from four subfamilies [erythroblastic leukemia viral (v-erb-b) oncogene homolog (ErbB), platelet-derived growth factor (PDGF), neurotrophic tyrosine kinase receptor (TRK), vascular endothelial growth factor (VEGF)] monitoring the interactions with five effectors (Grb2, p85, Stat5a, Shc46, PLCγ1). (aspetjournals.org)
  • Receptor tyrosine kinases (RTKs) represent a broad class of cell surface receptors that transduce signals across the cell membrane and regulate cell proliferation, survival, differentiation and migration ( Schlessinger, 2000 ). (aspetjournals.org)
  • Protein receptor tyrosine kinases (RTKs) are the largest class of enzyme-linked receptors, both receptors and enzymes that bind to ligands and phosphorylate tyrosine residues of target proteins. (creativebiomart.net)
  • All RPTKs are composed of three components: an extracellular domain containing a ligand binding site, a single transmembrane hydrophobic alpha helix region, and an intracellular domain containing tyrosine protein kinase (RTKs) activity. (creativebiomart.net)
  • Receptor tyrosine kinase (RTKs) is a high affinity cell surface receptor for many polypeptide growth factors, cytokines and hormones. (creativebiomart.net)
  • Receptor tyrosine-protein kinase Her2 (ErbB2) is a member of the ERBB family of receptor tyrosine kinases (RTKs). (nature.com)
  • The protein encoded by this gene is a member of the ALK/LTK receptor family of receptor tyrosine kinases (RTKs) whose ligand is unknown. (wikipedia.org)
  • Closely related to the insulin receptor family of RTKs. (wikipedia.org)
  • SU6668 is a cell-permeable indolinone compound that acts as a potent ATP-competitive inhibitor against RTKs (receptor tyrosine kinases) Kit, PDGFR, VEGFR2 (Flk-1KDR), FGFR1 activity in vitro (IC50 0.01, 0.1, 3.9, and 3.8 M, respectively) and PDGFVEGFbFGF-mediated angiogenesis and tumor development. (csnpharm.com)
  • ALW-II-41-27 is a novel Eph receptor tyrosine kinase inhibitor. (adooq.com)
  • IC 50 = 2 nmol/L). We found IMC-41A10 to be a potent inhibitor of receptor and downstream signaling, cell migration, and tumorigenesis. (aacrjournals.org)
  • Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. (uni-wuerzburg.de)
  • This increase was blocked by pretreatment with the selective PKC inhibitor chelerythrine, with the tyrosine kinase inhibitor Lavendustin A or with the Src family tyrosine kinase inhibitor PP2. (ox.ac.uk)
  • Tyrphostin AG1433 is a tyrosine kinases inhibitor and also a selective PDGFRβ and VEGFR-2 (Flk-1/KDR) inhibitor with IC50s of 5.0 μM and 9.3 μM, respectively. (csnpharm.com)
  • Erlotinib HCl is a directly acting inhibitor of human EGFR tyrosine kinase with an IC50 of 2 nM. (csnpharm.com)
  • BI-4020 is a noncovalent, new-generation, wild-type EGFR sparing, macrocyclic tyrosine kinase inhibitor. (csnpharm.com)
  • 1. A method of treating renal cell carcinoma or metastatic melanoma comprising co-administering to a patient a composition comprising IL-21 polypeptide and a composition comprising a tyrosine kinase inhibitor. (freepatentsonline.com)
  • Böhmer FD, Karagyozov L, Uecker A, Serve H, Botzki A, Mahboobi S, Dove S (2003) A single amino acid exchange inverts susceptibility of related receptor tyrosine kinases for the ATP site inhibitor STI-571. (springer.com)
  • With evidence supporting a critical role for PDGF in arterial repair and restenosis following angioplasty, we investigated the ability of a selective inhibitor of the PDGFr-tyrosine kinase (TK) to block restenosis following angioplasty. (ahajournals.org)
  • The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [ PMID: 15078142 ], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [ PMID: 15320712 ]. (ebi.ac.uk)
  • Receptor tyrosine kinase inhibitors as potent weapons in war against cancers. (ebi.ac.uk)
  • Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an increase in the phosphotyrosine content of many cellular proteins. (monash.edu)
  • The aim of this study was to investigate the role of platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) in the proliferation of human glioblastoma cells as a prerequisite for a new therapeutic approach to the treatment of malignant brain tumors with selective tyrosine kinase inhibitors such as imatinib. (springer.com)
  • The mitogen-activated protein kinase (MAPK) pathway is the canonical signaling pathway for many receptor tyrosine kinases, such as the Epidermal Growth Factor Receptor. (mdpi.com)
  • We will not only review the well-known members of the family, such as kinase suppressor of Ras (KSR), but also put a special focus on the function of the recently identified or less studied scaffolders, such as fibroblast growth factor receptor substrate 2, flotillin-1 and mitogen-activated protein kinase organizer 1. (mdpi.com)
  • 2004). The important feature of this model is that agents that disrupt GPCR function (e.g. pertussis toxin (PTX) and the C-terminal tail of GRK2, which sequesters Gbg subunits) block the growth factor-stimulated activation of various effector modules, such as p42/p44 mitogen activated protein kinase (p42/p44 MAPK) (Luttrell et al. (strath.ac.uk)
  • Following ligand binding and autophosphorylation, Met transmits intercellular signals using a unique multisubstrate docking site present within the C-terminal end of the receptor. (nih.gov)
  • Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. (rcsb.org)
  • GP30 is a potential ligand for this receptor. (rcsb.org)
  • Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within the cytoplasmic domains of the receptors. (nih.gov)
  • Moreover, this PDZ domain also interacts with C-terminal sequences derived from other transmembrane receptors such as neurexins and the Notch ligand Jagged. (pnas.org)
  • The Tie1 receptor tyrosine kinase was isolated over a decade ago, but so far no ligand has been found to activate this receptor. (sigmaaldrich.com)
  • The ligand for c-MET - Hepatocyte Growth Factor (HGF) as well as RON's ligand, MSP are members of the kringle-domain plasminogen-related protein family. (aacrjournals.org)
  • It is an orphan receptor with no known ligand, as it acts as a heterodimer with other members of the EGF receptors family. (perkinelmer.com)
  • RON ligand, macrophage-stimulating protein (MSP), was originally found to modulate the function of certain macrophage by a variety of means. (aacrjournals.org)
  • Pfleger and Eidne, 2006 ) and developed new whole-cell receptor tyrosine kinase assays, which enabled us to monitor in living cells the ligand-induced recruitment of downstream effector proteins to various members of the RTK superfamily. (aspetjournals.org)
  • The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. (researchandmarkets.com)
  • In many ways, extracellular ligand binding typically causes or stabilizes receptor dimerization. (creativebiomart.net)
  • The ligand-activated form of EphB2, which belongs to the Tyr family of protein kinases, interacts with multiple proteins, including GTPase-activating protein (RASGAP) through its SH2 domain. (biomol.com)
  • May act as a receptor for wnt ligand WNT5A which may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443). (nih.gov)
  • Ligand-induced conformational changes induce autophosphorylation on the tyrosine residue of the C-terminal domain, which serves as a platform for protein-protein interactions mediated by Src-domains resulting in the transfer of signaling through the PI3K/Akt pathways 8 . (nature.com)
  • The RET proto-oncogene product is a receptor tyrosine kinase representing the signal-transducing molecule of a multisubunit surface receptor complex for the glial cell line-derived neurotrophic factor (GDNF), in which a novel glycosyl-phosphatidylinositol (PI)-linked protein (termed GDNFR-alpha) acts as the ligand-binding component. (biomedsearch.com)
  • G Protein receptors and tyrosine kinase receptors both work to mediate cell communication by binding a signaling molecule, which is also called a ligand. (player.fm)
  • G proteins receptors are located in the cell membrane which is where an extracellular ligand binds to it. (player.fm)
  • Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. (rcsb.org)
  • We further observed that co-expression of LRIG1 with EGF receptor suppresses cellular receptor levels, shortens receptor half-life, and enhances ligand-stimulated receptor ubiquitination. (elsevier.com)
  • Restenosis following angioplasty occurs as a consequence of catheter-induced SMC migration, proliferation, matrix production, vasospasm, and remodeling, 1 2 events driven by inappropriate growth factor ligand and receptor expression. (ahajournals.org)
  • 8 9 Additionally, PDGFr activity, as determined by the state of receptor autophosphorylation, increases several days postinjury and persists for several weeks, 10 11 providing a functional link between expression of PDGFr/ligand mRNA 9 and proteins 10 11 and potential biological influence on arterial stenosis. (ahajournals.org)
  • Ligand-mediated dimerization of the Met receptor tyrosine kinase by the bacterial invasion protein InlB. (helmholtz-hzi.de)
  • rat chicken Human Zebrafish Caenorhabditis elegans Drosophila In common with other receptor tyrosine kinase family members, RYK is composed of three domains, an N-terminal, extracellular ligand-binding domain, a transmembrane spanning domain and a C-terminal intracellular domain. (wikipedia.org)
  • Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (ebi.ac.uk)
  • A mutational analysis revealed that six C-terminal residues of the receptors are involved in binding to the PDZ domain of AF6 in a sequence-specific fashion. (pnas.org)
  • Phosphotyrosine residues serve as binding sites for downstream signaling proteins that establish a complex network of interactions within the cell. (pnas.org)
  • These interactions are dependent on the RTK kinase activity and autophosphorylation of specific tyrosine residues in the carboxyl terminus. (aspetjournals.org)
  • Epidermal growth factor receptor (EGFR) BRET structure-function studies identify the tyrosine residues 1068, 1114, and 1148 as the main residues mediating the interaction of EGFR with the adapter protein Grb2. (aspetjournals.org)
  • Many of the RTK-effector protein interactions depend on the autophosphorylation of specific tyrosine residues in the intracellular carboxyl terminus of an RTK. (aspetjournals.org)
  • Since the RTK receptor phosphorylates multiple tyrosine residues, they can activate a variety of signal transduction pathways. (creativebiomart.net)
  • It binds RASGAP through the juxtamembrane tyrosines residues, and also interacts with PRKCABP and GRIP1 This type I membrane protein is expressed in brain, heart, lung, kidney, placenta, pancreas, liver and skeletal muscle. (biomol.com)
  • The 1,070-amino acid PTK7 polypeptide deduced from the cDNA sequence constitutes receptor protein tyrosine kinase (RPTK), but has several unusual residues in some of the highly conserved tyrosine kinase motifs. (elsevier.com)
  • The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. (wikipedia.org)
  • c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (wikipedia.org)
  • abstract = "Recent evidence suggests that signals transmitted by receptor tyrosine kinases (RTK) and G-protein coupled receptors (GPCR) are integrated to promote efficient growth factor stimulation of cellular responses (Waters et al. (strath.ac.uk)
  • This allows tyrosine in the cytoplasmic portion of each receptor monomer to be transphosphorylated by its chaperone to propagate signals through the plasma membrane. (creativebiomart.net)
  • Stimulation of B lymphocytes through their antigen receptor (BCR) result in rapid increases and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. (nii.ac.jp)
  • A catalytic protein-tyrosine kinase domain found on the cytoplasmic beta-portion of the insulin receptor. (lexic.us)
  • Proteins Kinase R (PKR) can be a broadly performing restriction aspect that phosphorylates the translation initiation aspect eIF2 in response to cytoplasmic double-stranded RNA (dsRNA), producing a stop to translation initiation and viral replication [7]. (biogeology.org)
  • The protein-tyrosine kinase activity of the purified cytoplasmic domain can be activated nearly 10-fold by 3 mM Mn 2+ in the presence or absence of 5 mM Mg 2+ . (elsevier.com)
  • We conclude that Mn 2+ ions, although they bind weakly, induce an activating conformational change in the secondary structure of the human insulin receptor cytoplasmic domain. (elsevier.com)
  • The protein-tyrosine kinase activity of the purified cytoplasmic domain can be activated nearly 10-fold by 3 mM Mn2+ in the presence or absence of 5 mM Mg2+. (elsevier.com)
  • The signal is eventually sent to a g protein which is located on the membrane, but on the cytoplasmic side. (player.fm)
  • The docking sites for both Jak1 and Stat6 reside in the cytoplasmic domain of the IL-4 receptor α- chain (IL-4Rα). (monash.edu)
  • By varying the autophosphorylation sequence of a phosphoPROTAC, it is conceivable that other receptor tyrosine kinase/effector pairings could be similarly exploited to achieve other biological effects. (nih.gov)
  • Autophosphorylation of Tyr-614 in the juxtamembrane region of the receptor generates a multi-docking-site for these interactions. (pnas.org)
  • The ontogeny of the structural and functional characteristics of insulin receptors is determined by examining insulin binding, subunit structure, autophosphorylation, and tyrosine-specific protein kinase activity in partially purified solubilized liver receptors from fetal (∼21 days postconception), neonatal (1- and 7-day-old), and adult rats. (diabetesjournals.org)
  • Insulin-stimulated autophosphorylation of insulin receptors was similar in the different groups. (diabetesjournals.org)
  • the PDGFr was purified from human VSMC and the final ATP concentration was 20 μmol/L. Inhibition of PDGFr-dependent activities, including in situ receptor autophosphorylation, mitogenesis, cell number, and viability were as described. (ahajournals.org)
  • 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)
  • HER2 interacts with other members of the EGFR family and functions as a co-receptor for epidermal growth factor or equivalent ligands. (ganfyd.org)
  • B.B., U.H., T.K., and K.S., unpublished data), which both bind specifically to the transmembrane subgroup of Eph-receptor ligands ( 5 , 6 ). (pnas.org)
  • Here, we have examined the potential of angiopoietins, ligands for the related Tie2 receptor, to mediate Tie1 activation. (sigmaaldrich.com)
  • Zurück zum Zitat Hafizi S, Dahlbäck B: Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. (springermedizin.de)
  • Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily. (springermedizin.de)
  • Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. (biomol.com)
  • The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. (biomol.com)
  • Few ligands for the extracellular regions of RPTPs are known, relegating most to the status of orphan receptors. (rupress.org)
  • 3 PDGF ligands, established as potent mitogens, chemotactic agents, and inducers of matrix synthesis, produce effects by dimerization and activation of PDGF-receptor (PDGFr) subunits. (ahajournals.org)
  • Results of immunocytochemical and in situ hybridization studies of human restenotic lesions 12 13 reveal the presence of PDGF-A and -B ligands and PDGFβr from 6 to 56 days following PTCA and the correspondent absence of proteins and mRNA in nonlesioned sites. (ahajournals.org)
  • The expression of both ligands and receptor in regions of vascular repair provides evidence that autocrine/paracrine loops promoting PDGF-driven cellular activities, occur in human restenotic lesions. (ahajournals.org)
  • Interactions have been described for the activated Eph-family members EphA2, EphA4, and EphB1 and the SH2-domain-containing proteins p85 subunit of phosphatidylinositol 3-kinase, the adapter protein SLAP, Grb2, Grb10, and Fyn ( 8 - 11 ). (pnas.org)
  • Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1 , leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. (rcsb.org)
  • 12 By phosphorylating IκBα, GRK5 may increase proatherogenic nuclear factor-κB (NF-κB) signaling downstream of Toll-like receptor 4 (TLR4) and tumor necrosis factor receptor-1 (TNFR1). (ahajournals.org)
  • These adaptor proteins associate RTK activation with downstream signal transduction pathways, such as the MAP kinase signaling cascade. (creativebiomart.net)
  • Downstream of the receptors, this pathway involves the activation of a kinase cascade that culminates in a transcriptional response and affects processes, such as cell migration and adhesion. (mdpi.com)
  • Moreover, a synthetic peptide containing this phosphoserine and its nearby tyrosine was found to be phosphorylated by the insulin receptor to a much lower extent than the same peptide without the phosphoserine. (nih.gov)
  • Activation of protein kinase C was found to stimulate by 10-fold the ability of a cytosolic kinase to phosphorylate this synthetic peptide as well as the intact insulin receptor substrate-1. (nih.gov)
  • These results indicate that activation of protein kinase C stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell, posing a potential mechanism for insulin resistance in some models of obesity. (nih.gov)
  • Specific 125 l-labeled insulin binding to these receptor preparations in the presence of different insulin concentrations was higher in fetal and neonatal rats compared with that in the adult rats. (diabetesjournals.org)
  • With fixed amounts of protein, the tyrosine-specific protein kinase activity in the presence of different insulin concentrations (1 × 10 −8 to 1 × 10 −6 M) was significantly higher in the fetal and neonatal rats than in adult rats. (diabetesjournals.org)
  • However, when expressed as a function of insulin-binding activity, the insulin-stimulated tyrosine-specific protein kinase activity in fetal and neonatal rats appears to be similar to that in adult rats because of decreased insulin binding in the latter group. (diabetesjournals.org)
  • These results demonstrate the structural and functional similarities of hepatic insulin receptors in fetal, neonatal, and adult rats. (diabetesjournals.org)
  • The relative differences in insulin-mediated biological functions in fetal and adult rat livers as reported previously are due to alterations ina step(s) distal to activation of insulin-receptor kinase. (diabetesjournals.org)
  • Results: Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). (uni-wuerzburg.de)
  • The divalent cation-binding properties of the human insulin receptor tyrosine kinase domain were examined kinetically and by electron paramagnetic resonance and circular dichroic spectroscopy. (elsevier.com)
  • Rosen, Ora M. / Mn 2+ -binding properties of a recombinant protein-tyrosine kinase derived from the human insulin receptor . (elsevier.com)
  • This group represents a group of known and predicted receptor-type tyrosine-protein kinases, including the EGF and ERB receptors, and the melanoma-inducing oncogene product XmrK. (ebi.ac.uk)
  • Abnormal expression of HER2 protein is thought to result in excess growth stimulation, converting HER2 into an oncogene . (ganfyd.org)
  • Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1) pipeline Target constitutes close to 23 molecules. (reportsweb.com)
  • Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1)-Receptor tyrosine-protein kinase erbB-3 or HER3 is a membrane bound protein encoded by the ERBB3 gene. (reportsweb.com)
  • It also reviews key players involved in Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsweb.com)
  • Additionally, the report provides an overview of key players involved in Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1) targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
  • The report analyses the pipeline products from therapy areas Oncology under development targeting Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1). (globalmarketsdirect.com)
  • The tyrosine kinase Met, the product of the c-met proto-oncogene and the receptor for hepatocyte growth factor/scatter factor (HGF/SF), mediates signals critical for cell survival and migration. (helmholtz-hzi.de)
  • The HER2 protein , also known amongst other names as, ErbB2 or neu, and coded for by the ERBB2 gene at 17q12 derives its name from human epidermal growth factor receptor 2 , indicating its similarity to epidermal growth factor receptor (EGFR). (ganfyd.org)
  • The AlphaLISA ® Human epidermal growth factor receptor 2 (ErbB-2, NEU, or HER2) Detection Kit is designed for detection and quantitation of human ErbB-2 in serum, buffered solution or cell culture medium in a homogeneous (no-wash steps, no separation steps) assay. (perkinelmer.com)
  • Human epidermal growth factor receptor 2 (ERBB2, NEU, or HER2) is a type I membrane glycoprotein that is a member of the ERBB family of tyrosine kinase receptors. (perkinelmer.com)
  • It serves as a receptor for the epidermal growth factor (EGF) family of growth factors. (perkinelmer.com)
  • Dr. Bipin G. Nair and Tarun B Patel, "Regulation of cardiac adenylyl cyclase by Epidermal Growth Factor (EGF): Role of EGF receptor protein tyrosine kinase activity", Biochemical pharmacology, vol. 46, pp. 1239-1245, 1993. (amrita.edu)
  • Previous genetic and biochemical studies indicate that Kekkon-1, a transmembrane protein containing leucine-rich repeats and an immunoglobulin-like domain in its extracellular region, acts as a feedback negative regulator of epidermal growth factor (EGF) receptor signaling in Drosophila melanogaster development. (elsevier.com)
  • 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)
  • Search proteins in UniProtKB for this molecule. (uniprot.org)
  • The latest report Ephrin Type B Receptor 4 - Pipeline Review, H1 2019, outlays comprehensive information on the Ephrin Type B Receptor 4 (Hepatoma Transmembrane Kinase or Tyrosine Protein Kinase TYRO11 or EPHB4 or EC 2.7.10.1) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchandmarkets.com)
  • once a signal molecule binds to the extracellular domain of the receptor, two monomeric receptor molecules form on the membrane. (creativebiomart.net)
  • Park, SK, Lee, HS & Lee, S-T 1996, ' Characterization of the human full-length PTK7 cDNA encoding a receptor protein tyrosine kinase-like molecule closely related to chick KLG ', Journal of Biochemistry , vol. 119, no. 2, pp. 235-239. (elsevier.com)
  • To start the process, a signalling molecule attaches to two tyrosine kinase receptors. (player.fm)
  • Analysis of how these adapter proteins bind to the Met receptor and what signal transducers they recruit have led to more substantial models of HGF/SF-Met signal transduction and have uncovered new potential pathways that may be involved into Met mediated tumor cell invasion and metastasis. (nih.gov)
  • Here we introduce phospho-dependent proteolysis targeting chimeras (phosphoPROTACs), a method to couple the conditional degradation of targeted proteins to the activation state of particular kinase-signaling pathways. (nih.gov)
  • We demonstrate the ability of these phosphoPROTACs to suppress the short- and long-term effects of their respective activating receptor tyrosine kinase pathways both in vitro and in vivo. (nih.gov)
  • They control the assembly of larger protein complexes that are involved in building, shaping, and directing specific RTK signaling pathways (illustrated in Fig. 1a ) ( Schlessinger, 2000 ). (aspetjournals.org)
  • These results suggest that pathways involving Eph-ephrin signalling may be important in the progression of colon cancer and that therapies that target this receptor may find application in anti-cancer treatments. (biomedcentral.com)
  • the interaction suppresses ERBB2 kinase activity (PubMed:26517842). (rcsb.org)
  • Finally, cytosolic extracts from the livers of ob/ob mice showed an 8-fold increase in a kinase activity capable of phosphorylating this synthetic peptide, compared to extracts of livers from lean litter mates. (nih.gov)
  • Activation of the co-receptor complex transduces a signal, which in turn, stimulates tyrosine kinase activity in the intracellular domain. (ganfyd.org)
  • In contrast to the association of EphB3 to the PDZ domain of AF6, the interaction with full-length AF6 clearly depends on the kinase activity of EphB3, suggesting a regulated mechanism for the PDZ-domain-mediated interaction. (pnas.org)
  • The binding of the PDZ domain does not depend on the catalytic activity of the receptors. (pnas.org)
  • In contrast, the kinase activity of EphB3 is required for high-affinity binding of full-length AF6, suggesting a novel regulated mechanism for PDZ-domain-mediated interactions. (pnas.org)
  • A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity. (umassmed.edu)
  • GRK5 activity in monocytes also reduced migration promoted by the 7-transmembrane receptor for monocyte chemoattractant protein-1 CC chemokine receptor-2. (ahajournals.org)
  • Conclusion- GRK5 attenuates atherosclerosis through multiple cell type-specific mechanisms, including reduction of SMC and endothelial cell NF-κB activity and desensitization of receptor-specific signaling through the monocyte CC chemokine receptor-2, macrophage CSF-1R, and the SMC platelet-derived growth factor receptor-β. (ahajournals.org)
  • 16 Lastly, GRK5 phosphorylates the platelet-derived growth factor receptor-β (PDGFRβ) and thereby alters signaling through this proatherogenic receptor tyrosine kinase in vascular smooth muscle cells (SMCs)-by reducing PDGFRβ-triggered inositol phosphate signaling, reducing PDGFRβ catalytic activity, and enhancing PDGFRβ-dependent Src activation. (ahajournals.org)
  • To our knowledge, this is the first demonstration that antibody-mediated inhibition of RON receptor tyrosine kinase activity negatively influences the proliferation of colon cancer cells in vitro and in vivo . (aacrjournals.org)
  • Employing purified protein phosphotyrosine phosphatase, and benzylidene derivatives (tyrphostins: compounds 11 and 12) that selectively inhibit EGF receptor protein tyrosine kinase (EGFRK) activity, the role of EGFRK in EGF-mediated stimulation of cardiac adenylyl cyclase was investigated. (amrita.edu)
  • Compounds 11 and 12, in a concentration-dependent manner, inhibited EGF receptor tyrosine kinase activity. (amrita.edu)
  • Thus, we conclude that protein tyrosine kinase activity of the EGF receptor is essential for the stimulation of cardiac adenylyl cyclase by EGF. (amrita.edu)
  • A limited number of whole-cell assays allow monitoring of receptor tyrosine kinase (RTK) activity in a signaling pathway-specific manner. (aspetjournals.org)
  • Other proteins that interact with the activating receptor act as adaptor proteins and have no intrinsic enzymatic activity by themselves. (creativebiomart.net)
  • In contrast, has also been shown to have very little tyrosine kinase activity in vitro. (nih.gov)
  • These drugs target either the homo- or heterodimerization of Her2 receptors or the receptors' RTK activity, both of them being critical for the proliferation of cancer cells. (nature.com)
  • In vitro kinase assays demonstrate that the specific kinase activity of syk increased eightfold after FcγRI cross-linking. (elsevier.com)
  • We propose that receptor-associated constitutive PTP activity functions to down-regulate persistent, receptor- linked kinase activity. (monash.edu)
  • Diliberto PA, Gordon GW, Yu CL, Earp HS, Herman B (1992) Platelet-derived growth factor (PDGF) alpha receptor activation modulates the calcium mobilizing activity of the PDGF beta receptor in Balb/c3T3 fibroblasts. (springer.com)
  • It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. (wikipedia.org)
  • However, in contrast to other receptor tyrosine kinases the C-terminal domain of RYK is devoid of detectable kinase activity. (wikipedia.org)
  • 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)
  • TYRO3 signaling plays an important role in various processes such as neuron protection from excitotoxic injury, platelet aggregation, cytoskeleton reorganization, inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. (marketresearchhub.com)
  • Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis. (ahajournals.org)
  • Thus, Stat6 activation by PV is an IL-4Rα-mediated, Jak1-dependent event that is independent of receptor dimerization. (monash.edu)
  • Structural basis of MET receptor dimerization by the bacterial invasion protein InlB and the HGF/SF splice variant NK1. (helmholtz-hzi.de)
  • 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 ErbB receptor family includes four members: ErbB1 (EGFR), ErbB2 (Her2), ErbB3, and ErbB4. (nature.com)
  • Abgent has over fifteen years of experience producing recombinant proteins in E. coli and mammalian cells (CHO and HEK293, etc), and we have added a powerful yeast expression platform to our menu of services. (abgent.com)
  • thus, it is of interest to know which effector functions of these cells can be triggered by these receptors when they interact with particles or surfaces covered with denatured proteins. (oalib.com)
  • By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. (biomol.com)
  • 17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30. (semanticscholar.org)
  • Violin plots show distribution of expression levels for Tyrosine-protein kinase receptor (SMED30029811) in cells (dots) of each of the 12 neoblast clusters. (stowers.org)
  • Expression of Tyrosine-protein kinase receptor (SMED30029811) in the t-SNE clustered sub-lethally irradiated X1 and X2 cells. (stowers.org)
  • Violin plots show distribution of expression levels for Tyrosine-protein kinase receptor (SMED30029811) in cells (dots) of each of the 10 clusters of sub-leathally irradiated X1 and X2 cells. (stowers.org)
  • Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment. (biomedsearch.com)
  • In the presence of GDNF-receptors derived from BMSC by PI-specific phospholipase C cleavage, GDNF efficiently bound RET-expressing AML blasts and was functionally active by reducing their clonogenic growth and triggering the monocytic maturation of leukemic cells. (biomedsearch.com)
  • In this report we show that γ-interferon (IFN) induces the expression of the nonreceptor protein tyrosine kinase, p72(syk), and that cross-linking the FcγRI receptor in IFN-differentiated U937 cells (U937IF cells) results in the activation of syk kinase. (elsevier.com)
  • These so-called MAPK scaffolding proteins are, thus, important coordinators of the signaling response in cells. (mdpi.com)
  • We observed that in co-transfected 203T cells, LBIG1 forms a complex with each of the ErbB receptors independent of growth factor binding. (elsevier.com)
  • Murine L929 cells, which do not express the γ common chain of the IL-4 receptor, support PV-mediated but not IL-4-dependent Stat6 activation. (monash.edu)
  • Denk PO, Knorr M (2002) Differential regulation of expression of PDGF receptors on corneal epithelial cells. (springer.com)
  • The human pathogen Listeria monocytogenes exploits Met signaling for invasion of host cells via its surface protein InlB. (helmholtz-hzi.de)
  • Using immunohistochemistry and Western analysis techniques with an EphB4-specific antibody, we also show that this receptor is expressed in the epithelial cells of the tumour tissue and either not at all, or in only low levels, in the normal tissue. (biomedcentral.com)
  • CGP 52411 inhibited the EGF-R protein-tyrosine kinase in vitro with high selectivity. (csnpharm.com)
  • This gene encodes a muscle-specific tyrosine kinase receptor. (nih.gov)
  • The related to receptor tyrosine kinase (RYK) gene encodes the protein Ryk. (wikipedia.org)
  • Posttranslational protein knockdown coupled to receptor tyrosine kinase activation with phosphoPROTACs. (nih.gov)
  • B ) Upon activation of the RTK, the phosphoPROTAC is phosphorylated, creating a binding site for the SH2- or PTB-domain-containing effector protein and its subsequent recruitment for ubiquitination by VHL and proteasomal degradation. (nih.gov)
  • Publications] Yamada,T.: 'Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM. (nii.ac.jp)
  • The early activation events that link receptor engagement and DC maturation are not well characterized. (pasteur.fr)
  • We have recently shown that potentiation of NMDA receptor function by protein kinase C (PKC) appears to be mediated via activation of non-receptor tyrosine kinases. (ox.ac.uk)
  • The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. (nih.gov)
  • For instance, the IGF-1 and FGF receptors use the G-protein, Gi to stimulate activation of p42/p44 MAPK in fibroblasts and skeletal muscle, respectively (Luttrell et al. (strath.ac.uk)
  • Background -Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. (ahajournals.org)
  • Full Met activation requires the additional C-terminal domains of InlB which induce heparin-mediated receptor clustering and potent signaling. (helmholtz-hzi.de)
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)
  • A gene on chromosome 5q35.3 that encodes a tyrosine kinase receptor for vascular endothelial growth factors (VEGF) C and D, which appear to play a role in lymphangiogenesis and maintenance of the lymphatic endothelium. (thefreedictionary.com)
  • Mutant p53 protein induces overexpression of HER2. (nature.com)
  • Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. (biomol.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)
  • Similarly, protein phosphotyrosine phosphatase obliterated the ability of EGF, but not isoproterenol, to stimulate adenylyl cyclase. (amrita.edu)
  • Tyrosine Protein Kinase Receptor TYRO3 (Tyrosine Protein Kinase BYK or Tyrosine Protein Kinase DTK or Tyrosine Protein Kinase RSE or Tyrosine Protein Kinase TIF or Tyrosine Protein Kinase SKY or TYRO3 or EC 2.7.10.1) pipeline Target constitutes close to 7 molecules. (marketresearchhub.com)
  • Tyrosine Protein Kinase Receptor TYRO3 (Tyrosine Protein Kinase BYK or Tyrosine Protein Kinase DTK or Tyrosine Protein Kinase RSE or Tyrosine Protein Kinase TIF or Tyrosine Protein Kinase SKY or TYRO3 or EC 2.7.10.1) - Tyrosine-protein kinase receptor TYRO3 is an enzyme encoded by the TYRO3 gene. (marketresearchhub.com)
  • Furthermore, this report also reviews key players involved in Tyrosine Protein Kinase Receptor TYRO3 (Tyrosine Protein Kinase BYK or Tyrosine Protein Kinase DTK or Tyrosine Protein Kinase RSE or Tyrosine Protein Kinase TIF or Tyrosine Protein Kinase SKY or TYRO3 or EC 2.7.10.1) targeted therapeutics development with respective active and dormant or discontinued projects. (marketresearchhub.com)
  • The global Tyrosine Protein Kinase Receptor TYRO3 market was valued at million US$ in 2018 and will reach million US$ by the end of 2025, growing at a CAGR of during 2019-2025. (researchreportcenter.com)
  • This report focuses on Tyrosine Protein Kinase Receptor TYRO3 volume and value at global level, regional level and company level. (researchreportcenter.com)
  • From a global perspective, this report represents overall Tyrosine Protein Kinase Receptor TYRO3 market size by analyzing historical data and future prospect. (researchreportcenter.com)
  • For each manufacturer covered, this report analyzes their Tyrosine Protein Kinase Receptor TYRO3 manufacturing sites, capacity, production, ex-factory price, revenue and market share in global market. (researchreportcenter.com)
  • The report Global Tyrosine Protein Kinase Receptor TYRO3 Market enlight crucial and distinct factors dominate the market growth forecast amount from 2018 to 2025. (sacramentotelescope.com)
  • These adapter proteins in turn recruit several signal transducing proteins to form an intricate signaling complex. (nih.gov)
  • Cellular interactions and signal transduction must be an important aspect of hindbrain segmentation, so we have screened for tyrosine kinases expressed in rhombomere-restricted patterns in the developing mouse embryo. (biologists.org)
  • An important signal transduction pathway contains the tyrosine kinase receptor c-met, which is required for the survival and proliferation of myoblasts during migration during muscle development. (creativebiomart.net)
  • which has a distinct structural character, that is the presence of the second src homology region 2 (SH2) instead of SH3, from other members of this group of PTK.Our efforts have in large part focused on the relationship between Syk in the context of surface receptor-initiated signal transduction in B cell and platelet because of their abundant localization. (nii.ac.jp)
  • The data suggest that p72(syk) is involved in signal transduction through the FcγRI receptor, involving the FcγRIγ subunit. (elsevier.com)
  • Then this signal is sent through a transduction pathway where the last target protein causes some response. (player.fm)
  • After the signal binds to the receptor, the receptor slightly changes shape and becomes active. (player.fm)
  • In this review, we summarize the recent advances in the research on MAPK/extracellular signal-regulated kinase (ERK) pathway scaffolders. (mdpi.com)
  • A kinase is a protein that phosphorylates other proteins. (player.fm)
  • For tyrosine kinase receptors, the kinase phosphorylates tyrosine. (player.fm)
  • Then, each tyrosine kinase receptor phosphorylates the domains of the tyrosine kinase receptor. (player.fm)
  • ROR1 and ROR2 are orphan receptor tyrosine kinases that are most closely related to MuSK and the Trk family of neurotrophin receptors. (creativebiomart.net)
  • Evaluation of type 1 growth factor receptor family expression in benign and malignant thyroid lesions. (semanticscholar.org)
  • Vascular Endothelial Growth Factor Receptor Family in Ascidians, Halocynthia roretzi (Sea Squirt). (mdpi.com)
  • Electron paramagnetic resonance spectra of the purified, acid-denatured kinase domain and assays of EDTA-treated kinase show that the purified protein does not possess residual, tightly bound Mn2+. (elsevier.com)
  • ErbB receptors are localized on the cell membrane surface as inactive monomers. (nature.com)
  • HER2 can be shed from the cell surface as a soluble protein (sHER2) via proteolytic cleavage by an unidentified protease. (perkinelmer.com)
  • The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. (rcsb.org)
  • HER2 can be blocked using a synthetic humanised monoclonal antibody called trastuzumab , although the mechanisms of action may be more complex than just receptor antagonism. (ganfyd.org)
  • The antibodies target the extracellular domain of the HER2 receptor. (perkinelmer.com)
  • The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2. (semanticscholar.org)
  • The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. (semanticscholar.org)
  • Out of those, 30-40% of breast cancer patients with overexpressed Her2 also have high levels of ER, while the rest exhibit diminished expressions of ER and PR hormone receptors, making them extremely resistant to targeting with antihormone therapy. (nature.com)
  • The Macrophage-Stimulating Protein receptor aka. (aacrjournals.org)
  • The macrophage-stimulating protein receptor (RON) belongs to the c-MET family of receptor tyrosine kinases ( 1 - 3 ). (aacrjournals.org)
  • Protein kinase function is evolutionarily conserved from Escherichia coli to human [ PMID: 12471243 ]. (ebi.ac.uk)
  • Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [ PMID: 12368087 ]. (ebi.ac.uk)
  • For example, the Src-family of protein-tyrosine kinases [ PMID: 15845350 ]. (ebi.ac.uk)
  • Then, the GDP binds to the g protein receptor. (player.fm)
  • To date, the information about signaling molecules mediating Eph-receptor-specific responses is still limited to a few family members. (pnas.org)
  • Ephrin Type B Receptor 4 (Hepatoma Transmembrane Kinase or Tyrosine Protein Kinase TYRO11 or EPHB4 or EC 2.7.10.1) pipeline Target constitutes close to 6 molecules. (researchandmarkets.com)
  • It also reviews key players involved in Ephrin Type B Receptor 4 (Hepatoma Transmembrane Kinase or Tyrosine Protein Kinase TYRO11 or EPHB4 or EC 2.7.10.1) targeted therapeutics development with respective active and dormant or discontinued projects. (researchandmarkets.com)
  • Additionally, the report provides an overview of key players involved in Ephrin Type B Receptor 4 (Hepatoma Transmembrane Kinase or Tyrosine Protein Kinase TYRO11 or EPHB4 or EC 2.7.10.1) targeted therapeutics development and features dormant and discontinued projects. (marketresearch.com)
  • The family has been classified in 8 major groups based on sequence comparison of their tyrosine (PTK) or serine/threonine (STK) kinase catalytic domains. (biomol.com)
  • previous studies have demonstrated that some components of the leukocyte cell membrane, cr3 (mac-1, cd11b/cd18) and p150/95, are able to bind to denatured proteins. (oalib.com)
  • We demonstrate that PTPα, an RPTP that dephosphorylates and activates src family kinases, forms a novel membrane-spanning complex with the neuronal GPI-anchored receptor contactin. (rupress.org)
  • The protein encoded by this gene is a receptor protein tyrosine kinase and type I transmembrane protein that belongs to the ROR subfamily of cell surface receptors. (nih.gov)
  • Based on molecular profiling breast carcinomas are divided into several subtypes depending on the expression of a number of cell surface receptors, e.g. (nature.com)
  • Despite lacking a transmembrane domain, GPI receptors can recruit intracellular src family tyrosine kinases to receptor complexes. (rupress.org)
  • Conclusion: Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. (uni-wuerzburg.de)
  • Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. (creativebiomart.net)
  • There are currently about 90 TK genes sequenced, 58 are of receptor protein TK (e.g. (biomol.com)
  • Src contains at least three flexible protein domains, which, in conjunction with myristoylation, can mediate attachment to membranes and determine subcellular localization. (wikipedia.org)
  • In the human glioblastoma cell lines U-87 MG, U-118 MG and U-373 MG different PDGF and PDGFR mRNAs were detected by RT-PCR, and the expression of the receptor proteins was demonstrated by immunostaining and flow cytometry. (springer.com)
  • Protein kinases are enzymes that transfer a phosphate group from a phosphate donor, generally the g phosphate of ATP, onto an acceptor amino acid in a substrate protein. (biomol.com)
  • The G protein is made up of three subunits: alpha, beta, and gamma. (player.fm)
  • Now the G protein is split into two parts: one part is the single alpha subunit and the other is the beta and gamma subunits. (player.fm)
  • The protein kinase complement of the human genome. (ebi.ac.uk)
  • Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. (ebi.ac.uk)
  • Pillars Article: The CD4 Receptor Is Complexed in Detergent Lysates to a Protein-Tyrosine Kinase (Pp58) from Human T Lymphocytes. (jimmunol.org)
  • Gas6, the protein product of the growth arrest specific gene 6, is present in human circulation at subnanomolar concentrations. (springermedizin.de)
  • G proteins coupled receptors are very important in the human body. (player.fm)
  • Here we tested whether the related human LRIG1 (also called Lig-1) protein can act as a negative regulator of EGF receptor and its relatives, ErbB2, ErbB3, and ErbB4. (elsevier.com)
  • Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. (helmholtz-hzi.de)
  • Tyrosine kinase receptors are enzyme linked receptors. (player.fm)
  • Enzyme linked receptors are receptors that are associated with an enzyme. (player.fm)
  • Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. (sigmaaldrich.com)
  • Reconstitute the lyophilized recombinant Cynomolgus Receptor protein-tyrosine kinase/CSF1R, His (HEK293-expressed) (rCynReceptor protein-tyrosine kinase/CSF1R, His) to 100 µg/mL using ddH 2 O. (medchemexpress.com)
  • Lyophilized recombinant Cynomolgus Receptor protein-tyrosine kinase/CSF1R, His (HEK293-expressed) (rCynReceptor protein-tyrosine kinase/CSF1R, His) is stored at -20°C. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer. (medchemexpress.com)
  • The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. (ebi.ac.uk)
  • Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. (ebi.ac.uk)
  • Protein kinases are enzymes that transfer a phosphate group from a phosphate donor, generally the. (biomol.com)
  • With state-of-the art molecular biology and protein biochemistry labs, we work with our clients to rapidly evaluate in parallel to identify the optimal expression system for candidate proteins. (abgent.com)
  • Glycosyl phosphatidylinositol (GPI)-linked receptors and receptor protein tyrosine phosphatases (RPTPs), both play key roles in nervous system development, although the molecular mechanisms are largely unknown. (rupress.org)
  • The molecular mechanisms by which mammalian receptor tyrosine kinases are negatively regulated remain largely unexplored. (elsevier.com)