src-Family Kinases: 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.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Proto-Oncogene Proteins c-hck: Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.Proto-Oncogene Proteins c-yes: 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).Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.src Homology Domains: 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.Proto-Oncogene Proteins pp60(c-src): 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.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Signal Transduction: 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.Phosphatidylinositol 3-Kinases: 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.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): 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.Pyrimidines: 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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Proto-Oncogene Proteins: 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.MAP Kinase Signaling System: 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.Enzyme Activation: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Phosphotyrosine: 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.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Focal Adhesion Kinase 1: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Protein Binding: 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.Calcium-Calmodulin-Dependent Protein Kinases: 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)Intracellular Signaling Peptides and Proteins: 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.Protein Kinase C: 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.Crk-Associated Substrate Protein: Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.Phosphoproteinsp38 Mitogen-Activated Protein Kinases: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cells, Cultured: 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.Adaptor Proteins, Signal Transducing: 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 enzymesMitogen-Activated Protein Kinase 1: 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.Focal Adhesion Kinase 2: 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.Phospholipase C gamma: 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.ThiazolesAmino Acid Sequence: 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.Molecular Sequence Data: 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.Transfection: 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.Proto-Oncogene Proteins c-abl: 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.Mitogen-Activated Protein Kinases: 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).Cell Adhesion: Adherence of cells to surfaces or to other cells.Genes, src: 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.Extracellular Signal-Regulated MAP Kinases: 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.JNK Mitogen-Activated Protein Kinases: 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.Precipitin Tests: 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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Recombinant Fusion Proteins: 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.Mitogen-Activated Protein Kinase Kinases: 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.Mitogen-Activated Protein Kinase 3: 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.Protein Structure, Tertiary: 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.3T3 Cells: 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.Membrane Microdomains: Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Blotting, Western: 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.Mutation: 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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Cyclic AMP-Dependent Protein Kinases: 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.Immunoblotting: 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.Proto-Oncogene Proteins c-cbl: 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.Proto-Oncogene Proteins c-akt: 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.Oncogene Protein pp60(v-src): 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.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Protein Tyrosine Phosphatases: 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.Mice, Knockout: 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.Cortactin: A microfilament protein that interacts with F-ACTIN and regulates cortical actin assembly and organization. It is also an SH3 DOMAIN containing phosphoprotein, and it mediates tyrosine PHOSPHORYLATION based SIGNAL TRANSDUCTION by PROTO-ONCOGENE PROTEIN PP60(C-SRC).Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.COS Cells: 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).)Receptor, Epidermal Growth Factor: 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.p21-Activated Kinases: 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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Antigens, CD45: 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.Benzodioxoles: Compounds based on benzene fused to oxole. They can be formed from methylated CATECHOLS such as EUGENOL.Models, Biological: 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.MAP Kinase Kinase Kinases: 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).Kinetics: The rate dynamics in chemical or physical systems.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Paxillin: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Tumor Cells, Cultured: 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.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Membrane Proteins: 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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Protein Tyrosine Phosphatase, Non-Receptor Type 11: 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.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Starfish: Echinoderms having bodies of usually five radially disposed arms coalescing at the center.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Apoptosis: 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.Calcium: 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.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.CDC2 Protein Kinase: 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.Cyclin-Dependent Kinases: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Mice, Inbred C57BLReceptor-Like Protein Tyrosine Phosphatases, Class 4: A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.GRB2 Adaptor Protein: 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).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.rac1 GTP-Binding Protein: A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 3.6.1.47.Peptide Mapping: 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.Receptors, Antigen, T-Cell: 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.Indoles: 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.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Protein Tyrosine Phosphatase, Non-Receptor Type 6: 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.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Protein Processing, Post-Translational: 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.Type C Phospholipases: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Receptors, IgE: Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).Time Factors: Elements of limited time intervals, contributing to particular results or situations.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Proteins: 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.Janus Kinase 2: 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.Ribosomal Protein S6 Kinases: 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.Receptor-Like Protein Tyrosine Phosphatases, Class 3: A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Proto-Oncogene Proteins c-kit: 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.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Vanadates: 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.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.Cell Degranulation: The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.T-Lymphocytes: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Cell Survival: 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.Receptors, Antigen, B-Cell: 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.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Gene Expression Regulation: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Down-Regulation: 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.Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.Proto-Oncogene Proteins c-crk: Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. c-crk protein is closely related to ONCOGENE PROTEIN V-CRK and includes several alternatively spliced isoforms.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.STAT3 Transcription Factor: 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.cdc42 GTP-Binding Protein: A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Cell Adhesion Molecules: 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.DNA Primers: 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.DNA-Binding Proteins: 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.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Receptor, Macrophage Colony-Stimulating Factor: A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.Octoxynol: Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy-1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Octoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Cell Line, Transformed: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Retinoblastoma-Like Protein p130: A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. RBL2 contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and E2F5 TRANSCRIPTION FACTOR. RBL2 also interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Rats, Sprague-Dawley: 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.I-kappa B Kinase: A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.RNA, Messenger: 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.Epidermal Growth Factor: 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.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Proto-Oncogene Proteins c-vav: Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.Cloning, Molecular: 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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Fusion Proteins, bcr-abl: 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.Cell Transformation, Neoplastic: 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.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Receptors, Platelet-Derived Growth Factor: 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.rap1 GTP-Binding Proteins: A genetically related subfamily of RAP GTP-BINDING PROTEINS that share homology with RAS PROTEINS. They bind to Ras effectors but do not activate them, therefore they may antagonize the effects of RAS PROTEINS. This enzyme was formerly listed as EC 3.6.1.47.Peptides: 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.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Receptor-CD3 Complex, Antigen, T-Cell: Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.Neural Cell Adhesion Molecule L1: A member of the immunoglobulin superfamily of neuronal cell adhesion molecules that is required for proper nervous system development. Neural cell adhesion molecule L1 consists of six Ig domains, five fibronectin domains, a transmembrane region and an intracellular domain. Two splicing variants are known: a neuronal form that contains a four-amino acid RSLE sequence in the cytoplasmic domain, and a non-neuronal form that lacks the RSLE sequence. Mutations in the L1 gene result in L1 disease. Neural cell adhesion molecule L1 is predominantly expressed during development in neurons and Schwann cells; involved in cell adhesion, neuronal migration, axonal growth and pathfinding, and myelination.Serine: 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.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Benzamides: BENZOIC ACID amides.Dystrophin-Associated Proteins: A group of proteins that associate with DYSTROPHIN at the CELL MEMBRANE to form the DYSTROPHIN-ASSOCIATED PROTEIN COMPLEX.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Neurons: 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.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)PiperazinesLigands: 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)Fertilization: The fusion of a spermatozoon (SPERMATOZOA) with an OVUM thus resulting in the formation of a ZYGOTE.Sulfonamides: A group of compounds that contain the structure SO2NH2.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.

Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. (1/4322)

Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell receptor (TCR), endogenous Cbl-b becomes rapidly tyrosine-phosphorylated. In heterogeneous COS-1 cells, Cbl-b was phosphorylated on tyrosine residues by both Syk- (Syk/Zap-70) and Src- (Fyn/Lck) family kinases, with Syk kinase inducing the most prominent effect. Syk associates and phosphorylates Cbl-b in Jurkat T cells. A Tyr-316 Cbl-binding site in Syk was required for the association with and for the maximal tyrosine phosphorylation of Cbl-b. Mutation at a loss-of-function site (Gly-298) in Cbl-b-N disrupts its interaction with Syk. Cbl-b constitutively binds Grb2 and becomes associated with Crk-L upon TCR stimulation. The Grb2- and the Crk-L-binding regions were mapped to the C-terminus of Cbl-b. The Crk-L-binding sites were further determined to be Y655DVP and Y709KIP, with the latter being the primary binding site. Taken together, these results implicate that Cbl-b is involved in TCR-mediated intracellular signaling pathways.  (+info)

Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530. (2/4322)

Elevated levels of Src kinase activity have been reported in a number of human cancers, including colon and breast cancer. We have analysed four human breast tumor cell lines that exhibit high levels of Src kinase activity, and have determined that these cell lines also exhibit a high level of a phosphotyrosine phosphatase activity that recognizes the Src carboxy-terminal P-Tyr530 negative regulatory site. Total Src kinase activity in these cell lines is elevated as much as 30-fold over activity in normal control cells and specific activity is elevated as much as 5.6-fold. When the breast tumor cells were grown in the presence of the tyrosine phosphatase inhibitor vanadate, Src kinase activity was reduced in all four breast tumor cell lines, suggesting that Src was being activated by a phosphatase which could recognize the Tyr530 negative regulatory site. In fractionated cell extracts from the breast tumor cells, we found elevated levels of a membrane associated tyrosine phosphatase activity that preferentially dephosphorylated a Src family carboxy-terminal phosphopeptide containing the regulatory tyrosine 530 site. Src was hypophosphorylated in vivo at tyrosine 530 in at least two of the tumor cell lines, further suggesting that Src was being activated by a phosphatase in these cells. In preliminary immunoprecipitation and antibody depletion experiments, we were unable to correlate the major portion of this phosphatase activity with several known phosphatases.  (+info)

C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. (3/4322)

Increased expression of the insulin-like growth factor-I receptor (IGF-IR) protein-tyrosine kinase occurs in several kinds of cancer and induces neoplastic transformation in fibroblast cell lines. The transformed phenotype can be reversed by interfering with the function of the IGF-IR. The IGF-IR is required for transformation by a number of viral and cellular oncoproteins, including SV40 large T antigen, Ras, Raf, and Src. The IGF-IR is a substrate for Src in vitro and is phosphorylated in v-Src-transformed cells. We observed that the IGF-IR and IR associated with the C-terminal Src kinase (CSK) following ligand stimulation. We found that the SH2 domain of CSK binds to the tyrosine-phosphorylated form of IGF-IR and IR. We determined the tyrosine residues in the IGF-IR and in the IR responsible for this interaction. We also observed that fibroblasts stimulated with IGF-I or insulin showed a rapid and transient decrease in c-Src tyrosine kinase activity. The results suggest that c-Src and CSK are involved in IGF-IR and IR signaling and that the interaction of CSK with the IGF-IR may play a role in the decrease in c-Src activity following IGF-I stimulation.  (+info)

Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. (4/4322)

Collagen-related peptide (CRP), a collagen homologue, induces platelet activation through a tyrosine kinase-dependent pathway, leading to sequential tyrosine phosphorylation of Fc receptor (FcR) gamma-chain, Syk, and phospholipase C-gamma2. Here we report that CRP and the platelet low affinity immune receptor FcgammaRIIA stimulate tyrosine phosphorylation of the T cell adapter SLP-76, whereas the G protein-coupled receptor agonist thrombin induces only minor tyrosine phosphorylation. This suggests that SLP-76 has a specific role downstream of receptors that signal via an immunoreceptor tyrosine-based activation motif. Immunoprecipitation studies demonstrate association of SLP-76 with SLAP-130, Vav, Fyn, Lyn, and the FcR gamma-chain in CRP-stimulated platelets. Several of these proteins, including SLP-76, undergo tyrosine phosphorylation in in vitro kinase assays performed on SLP-76 immunoprecipitates. Tyrosine phosphorylation of all of these proteins in the in vitro kinase assay was abrogated by the Src family kinase inhibitor PP1, suggesting that it is mediated by either Fyn or Lyn. The physiological significance of this is uncertain, however, since tyrosine phosphorylation of SLP-76 in vivo is not altered in either Fyn- or Lyn-deficient platelets. CRP stimulation of Syk-deficient platelets demonstrated that in vivo tyrosine phosphorylation of SLP-76 is downstream of Syk. The absence of Syk in the SLP-76 immunoprecipitates raises the possibility that another protein is responsible for bringing SLP-76 to Syk. Candidates for this include those proteins that co-immunoprecipitate with SLP-76, including the FcR gamma-chain. Tyrosine phosphorylation of PLC-gamma2 and Ca2+ mobilization is markedly attenuated in SLP-76-deficient platelets following CRP stimulation, suggesting that the adapter plays a critical role in the regulation of the phospholipase. The increase in tyrosine phosphorylation of SLAP-130 in response to CRP is also inhibited in SLP-76-deficient platelets, placing it downstream of SLP-76. This work identifies SLP-76 as an important adapter molecule that is regulated by Syk and lies upstream of SLAP-130 and PLC-gamma2 in CRP-stimulated platelets.  (+info)

Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. (5/4322)

In order to evaluate the involvement of c-yes and c-erbB-2 oncogene products, and p53 tumor suppressor protein in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 79 mammary tumors were analyzed immunohistochemically using antibodies against human c-yes p62 and c-erbB-2 products and p53. These 79 tumors were divided into 2 groups: 32 benign (2 adenosis, 7 simple adenomas, 14 complex adenomas, and 9 benign mixed mammary tumors) and 47 malignant tumors (26 simple adenocarcinomas, 7 complex adenocarcinomas, 5 solid carcinomas, 2 sclerosing carcinomas, 6 malignant mixed mammary tumors, and 1 malignant myoepithelioma). As a result of immunostaining, 40.6% (13/32) of the benign tumors and 21.3% (10/47) of the malignant tumors expressed the c-Yes oncogene product, ErbB-2 expression was detected in 50% (16/32) of the benign tumors and in 19.1% (9/47) of the malignant tumors. P53 expression was detected in 16% (4/25) of the benign tumors and in 30.6% (11/36) of the malignant tumors. Co-expression of c-Yes and ErbB-2, ErbB-2 and p53, and all 3 products was detected in 6, 1 and 7 tumors, respectively.  (+info)

Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase. (6/4322)

We report here that cultured airway smooth muscle cells contain transcripts of endothelial differentiation gene 1 (EDG-1), a prototypical orphan Gi-coupled receptor whose natural ligand is sphingosine 1-phosphate (S1P). This is consistent with data that showed that S1P activated both c-Src and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) in a pertussis toxin (PTX)-sensitive manner in these cells. An essential role for c-Src was confirmed by using the c-Src inhibitor, PP1, which markedly decreased p42/p44 MAPK activation. We have also shown that phosphoinositide 3-kinase (PI-3K) inhibitors (wortmannin and LY294002) decreased p42/p44 MAPK activation. An essential role for PI-3K was supported by experiments that showed that PI-3K activity was increased in Grb-2 immunoprecipitates from S1P-stimulated cells. Significantly, Grb-2 associated PI-3K activity was decreased by pretreatment of cells with PTX. Finally, we have shown that the co-stimulation of cells with platelet-derived growth factor (PDGF) and S1P (which failed to stimulate DNA synthesis) elicited a larger p42/p44 MAPK activation over a 30 min stimulation compared with each agonist alone. This was associated with a S1P-dependent increase in PDGF-stimulated DNA synthesis. These results demonstrate that S1P activates c-Src and Grb-2-PI-3K (intermediates in the p42/p44 MAPK cascade) via a PTX-sensitive mechanism. This action of S1P is consistent with the stimulation of EDG-1 receptors. S1P might also function as a co-mitogen with PDGF, producing a more robust activation of a common permissive signal transduction pathway linked to DNA synthesis.  (+info)

In situ detection of activated Bruton's tyrosine kinase in the Ig signaling complex by phosphopeptide-specific monoclonal antibodies. (7/4322)

Bruton's tyrosine kinase (Btk) is a critical transducer of signals originating from the B cell antigen receptor (BCR). Dosage, sequential phosphorylation, and protein interactions are interdependent mechanisms influencing Btk function. Phosphopeptide-specific mAbs recognizing two distinct phosphotyrosine modifications were used to quantify Btk activation by immunofluorescent techniques during B cell stimulation. In a population of cultured B cells stimulated by BCR crosslinking and analyzed by flow cytometry, transient phosphorylation of the regulatory Btk tyrosine residues (551Y and 223Y) was detected. The kinetics of phosphorylation of the residues were temporally distinct. Tyrosine 551, a transactivating substrate site for Src-family kinases, was maximally phosphorylated within approximately 30 seconds of stimulation as monitored by flow cytometry. Tyrosine 223, an autophosphorylation site within the SH3 domain, was maximally phosphorylated at approximately 5 minutes. Btk returned to a low tyrosine phosphorylation level within 30 minutes, despite persistent elevation of global tyrosine phosphorylation. Colocalization of activated Btk molecules with the crosslinked BCR signaling complex was observed to coincide with the period of maximal Btk tyrosine phosphorylation when stimulated B cells were analyzed with confocal microscopy. The results of these in situ temporal and spatial analyses imply that Btk signaling occurs in the region of the Ig receptor signaling complex, suggesting a similar location for downstream targets of its activity.  (+info)

Growth factor-mediated Fyn signaling regulates alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression in rodent neocortical neurons. (8/4322)

Src-family protein tyrosine kinases (PTKs) transduce signals to regulate neuronal development and synaptic plasticity. However, the nature of their activators and molecular mechanisms underlying these neural processes are unknown. Here, we show that brain-derived neurotrophic factor (BDNF) and platelet-derived growth factor enhance expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor 1 and 2/3 proteins in rodent neocortical neurons via the Src-family PTK(s). The increase in AMPA receptor levels was blocked in cultured neocortical neurons by addition of a Src-family-selective PTK inhibitor. Accordingly, neocortical cultures from Fyn-knockout mice failed to respond to BDNF whereas those from wild-type mice responded. Moreover, the neocortex of young Fyn mutants exhibited a significant in vivo reduction in these AMPA receptor proteins but not in their mRNA levels. In vitro kinase assay revealed that BDNF can indeed activate the Fyn kinase: It enhanced tyrosine phosphorylation of Fyn as well as that of enolase supplemented exogenously. All of these results suggest that the Src-family kinase Fyn, activated by the growth factors, plays a crucial role in modulating AMPA receptor expression during brain development.  (+info)

BioAssay record AID 242624 submitted by ChEMBL: Inhibition of fluorescent (GpYEEI) binding to Src protein tyrosine kinase SH2 domain.
TY - JOUR. T1 - Csk-binding protein controls red blood cell development via regulation of Lyn tyrosine kinase activity. AU - Plani-Lam, Janice H. C.. AU - Slavova-Azmanova, Neli S.. AU - Kucera, Nicole. AU - Louw, Alison. AU - Satiaputra, Jiulia. AU - Singer, Peter. AU - Lam, Kong Peng. AU - Hibbs, Margaret L.. AU - Ingley, Evan. PY - 2017/2/1. Y1 - 2017/2/1. N2 - Erythropoiesis is controlled principally through erythropoietin (Epo) receptor signaling, which involves Janus kinase 2 (JAK2) and Lyn tyrosine kinase, both of which are important for regulating red blood cell (RBC) development. Negative regulation of Lyn involves C-Src kinase (Csk)-mediated phosphorylation of its C-terminal tyrosine, which is facilitated by the transmembrane adaptor Csk-binding protein (Cbp). Although Cbp has significant functions in controlling Lyn levels and activity in erythroid cells in vitro, its importance to primary erythroid cell development and signaling has remained unclear. To address this, we assessed the ...
TY - JOUR. T1 - Docking-based substrate recognition by the catalytic domain of a protein tyrosine kinase, C-terminal Src kinase (Csk). AU - Lee, Sungsoo. AU - Ayrapetov, Marina K.. AU - Kemble, David J.. AU - Parang, Keykavous. AU - Sun, Gongqin. PY - 2006/3/24. Y1 - 2006/3/24. N2 - Protein tyrosine kinases are key enzymes of mammalian signal transduction. Substrate specificity is a fundamental property that determines the specificity and fidelity of signaling by protein tyrosine kinases. However, how protein tyrosine kinases recognize the protein substrates is not well understood. C-terminal Src kinase (Csk) specifically phosphorylates Src family kinases on a C-terminal Tyr residue, which down-regulates their activities. We have previously determined that Csk recognizes Src using a substrate-docking site away from the active site. In the current study, we identified the docking determinants in Src recognized by the Csk substrate-docking site and demonstrated an interaction between the docking ...
Вид документа : Однотомное издание Шифр издания : K Автор(ы) : Pessa-Morikawa T. Заглавие : G proteins and Src-family protein tyrosine kinases in T lymphocytes:Regulation during differentation a.cell activation Выходные данные : Helsinki: Finn.soc.of sciences a.letters, 1993 Колич.характеристики :III,72 c: ил Серия: Commentationes phys.-math.et chem.-med., ISSN 0788-5717;N144 Примечания : ; Библиогр.:с.54-72 ISBN, Цена 951-653-253-5: Б.ц. ГРНТИ : ; 34.39.27 УДК : Ключевые слова (Своб.индексиров.): 0 ; протеин тирозинкиназы Перейти к источнику в Интернете: G proteins and Src-family protein tyrosine kinases in T lymphocytes:Regulation during differentation a.cell activation, Перейти к источнику в Интернете: , Перейти к источнику в Интернете: , ...
TY - JOUR. T1 - Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release. AU - Cheng, Haiying. AU - Straub, Susanne G.. AU - Sharp, Geoffrey W G. PY - 2007/3. Y1 - 2007/3. N2 - Both neurotransmitter release and insulin secretion occur via regulated exocytosis and share a variety of similar regulatory mechanisms. It has been suggested that Src family tyrosine kinases inhibit neurotransmitter release from neuronal cells (H. Ohnishi, S. Yamamori, K. Ono, K. Aoyagi, S. Kondo, and M. Takahashi. Proc Natl Acad Sci USA 98: 10930-10935, 2001). Thus the potential role of Src family kinases in the regulation of insulin secretion was investigated in this study. Two structurally different inhibitors of Src family kinases, SU-6656 and PP2, but not the inactive compound, PP3, enhanced Ca 2+-induced insulin secretion in both rat pancreatic islets and INS-1 cells in a concentration-dependent and time-dependent manner. Furthermore, Src family kinase-mediated insulin secretion appears to ...
We have demonstrated that in the H526 SCLC cell line, Lck activity is required for SCF-stimulated MAPK activation using two complementary techniques: (a) although activation of both Kit and MAPK were sensitive to inhibition by the tyrosine kinase inhibitor PP1, MAPK inhibition occurred at a lower PP1 concentration; this greater sensitivity to PP1 could be partially reversed by overexpression of Lck; and (b) inducible expression of a kinase-inactive DN Lck protein blocked SCF-mediated MAPK activation in a dose-dependent fashion. Although these observations run contrary to the dogma that receptor tyrosine kinases activate the Ras-MAPK pathway directly, they are consistent with a large body of data that demonstrates the importance of Src kinases in signaling from class-III RTKs, including the PDGFR, CSF-1R, and Kit. In murine fibroblasts expressing the PDGFR or the CSF-1R, interaction with their respective ligands recruits Src family kinases to the activated receptors and results in an increase in ...
The kinetics of CHC phosphorylation in activated T cells was slow compared with the total protein tyrosine phosphorylation in cell lysates (not depicted). This delay suggested that other signaling events are initiated before CHC phosphorylation. We had previously found that the activation of c-Src kinase or Lyn kinase, a Src kinase family member, was required for CHC phosphorylation after EGFR and BCR stimulation, respectively (20, 21). To address whether the activity of a Src family kinase was necessary for CHC phosphorylation in activated T cells, we treated Jurkat cells with various concentrations of the Src family kinase inhibitor PP1 before stimulation with soluble anti-CD3 Ab. At increasing concentrations of PP1, but not the serine/threonine kinase inhibitor H7, the level of inducible CHC phosphorylation was diminished (Fig. 2 A). Additionally, in the presence of PP1, the basal level of CHC phosphorylation in Jurkat cells before the induction of TCR internalization was also decreased, ...
Protein-tyrosine kinase C-terminal Src kinase (Csk) was originally purified as a kinase for phosphorylating Src and other Src family kinases. The phosphorylation of a C-terminal tyrosine residue of Src family kinases suppresses their kinase activity. Therefore, most physiological studies regarding Csk function have been focused on Csk as a negative regulator of Src family tyrosine kinases and as a potential tumor suppressor. Paradoxically, the protein levels of Csk were elevated in some human carcinomas. In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus ...
... and is currently a target of anti-invasive therapies. These outcomes indicate that although raised Src kinase activity is usually needed to focus on actin-associated meats to pre-invadopodia, controlled Src activity is certainly needed for invadopodia matrix and growth destruction activity. Our results explain a previously unappreciated function for proto-oncogenic Src in allowing the intrusive activity of constitutively energetic Src alleles. represents the true amount of cells analyzed within each experimental group. Antibodies and traditional western blotting Traditional western blotting of cell lysates was executed as referred to (Rothschild et al., 2006). The pursuing antibodies had been utilized: 4F11, Src clone GD11 (Upstate); -actin (Calbiochem); Living Shades GFP duplicate JL-8 (BD); Cort-pY421, Src-pY418 (Biosource); bird Src duplicate EC10 (Millipore) and Yes, Fyn (Cell Signaling). Plasmids The SrcCGFP ...
A wide range of extracellular signals are transduced by G protein-coupled receptors (GPCRs). When activated by ligands, GPCRs can activate associated heterotrimeric guanine nucleotide-binding proteins (G proteins), which in turn act on various effectors. Increasing evidence indicates that GPCRs also signal independently of heterotrimeric G proteins. Several GPCRs directly interact with Src-family kinases. Here, we discuss the evidence for direct interaction and activation of Src-family kinases by GPCRs and data that suggest that agonist dosage provides a mechanism by which GPCRs can switch between G protein-dependent and G protein-independent signaling.. ...
Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q up-regulated tyrosine kinase signaling through PDGFR signaling, which was blockable by
The non-receptor tyrosine kinase Src phosphorylates the newly discovered and described GTPase activating protein (GAP) ARHGAP42 that targets RhoA, among other Rho family GTPases, on tyrosine residue 376 which results in activation of ARHGAP42 which in turn de-activates GTP-bound (active) RhoA and correlates with increased cell motility that relies upon dynamic changes in the actin cytoskeleton and focal adhesions, changes involving RhoA signaling.
In the present study, we investigate the mechanism for the protein kinase A (PKA)-mediated activation of C-terminal Src kinase (Csk). Although isolated Csk kinase domain was phosphorylated at Ser364 by PKA to the same stoichiometry as wild-type Csk, significant activation of the isolated Csk kinase domain by PKA was observed only in the presence of the purified Src homology 3 domain (SH3 domain). Furthermore, the interaction between the SH3 and kinase domains was facilitated by PKA-mediated phosphorylation of the kinase domain, as evaluated by surface plasmon resonance. This suggests that an overall structural domain organization and interaction between the kinase and SH3 domains are important for the activity of Csk and its regulation by PKA.. ...
Ma Y.C., Huang X.Y.. Src tyrosine kinase is a critical signal transducer that modulates a wide variety of cellular functions. Misregulation of Src leads to cell transformation and cancer. Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are another group of signaling molecules that transduce signals from cell-surface receptors to generate physiological responses. Recently, it was discovered that G alpha s and G alpha i could directly stimulate Src family tyrosine kinase activity. This novel regulation of Src tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling mechanisms involved in ligand-induced receptor desensitization, internalization and other physiological processes.. Cell. Mol. Life Sci. 59:456-462(2002) [PubMed] [Europe PMC] ...
The identification of small molecules that alter T cell interactions with APCs represents an intriguing therapeutic strategy for autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE). Indeed, a recent study has highlighted the critical importance of T cell and APC contact duration in determining T cell fate in vivo and the development of T cell tolerance or activation (9). There are currently no known small molecules that reverse the T cell stop signal in clinical use, and the addition of such drugs to treat autoimmune diseases is particularly attractive given the high cost of biologic agents and the resultant burden on the healthcare system. In this study, we have identified at least three distinct classes of "reverse-stop" small molecules that impair TCR-induced T cell arrest but not random T cell motility: 1) Src family tyrosine kinase inhibitors, 2) microtubule depolymerizing agents, and 3) PGs. These compounds act in contrast with inhibitors of ...
Src tyrosine kinases transmit integrin-dependent signals pivotal for cell movement and proliferation. Here, we establish a mechanism for Src activation by integrins. c-Src is shown to bind constitutively and selectively to beta3 integrins through an interaction involving the c-Src SH3 domain and the …
c-Src and Lyn will be the only Src family kinases (SFKs) with established activity in osteoclasts (OCs). RANK Gandotinib ligand (RANKL)-induced differentiation attended by suppressed activation of the osteoclastogenic signaling molecules c-Jun and NF-κB. The anti-apoptotic properties of RANKL are also compromised in cells deleted of Fyn an event mediated by increased Bim expression and failed activation of Akt. The defective osteoclastogenesis of Fyn-/- OCs dampens bone resorption in vitro. Finally while Fyn deficiency does not regulate basal osteoclastogenesis in vivo it reduces that stimulated by RANKL by approximately 2/3. Thus Fyn is usually a pro-resorptive SFK which exerts its effects by prompting proliferation and differentiation while attenuating apoptosis of OC lineage cells. Keywords: Gandotinib Osteoclasts Fyn Src family kinase (SFK) M-CSF RANK ligand OCs are multinucleated hematopoietic cells with the unique capacity to degrade bone. They are generated under the aegis of M-CSF and ...
Src (proto-oncogene tyrosine-protein kinase) family is a family of non-receptor tyrosine kinases including nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. In immune cells, Src-family kinases (SFKs) have been implicated as critical regulators of a large number of intracellular signaling pathways. Src-family kinases (SFKs) occupy a proximal position in numerous signaling transduction cascades including those emanating from the T and B cell antigen receptors, Fc receptors, growth factor receptors, cytokine receptors, and integrins.
Cross-linking of the neutrophil-beta 2- or beta 3-related leukocyte response integrins by extracellular matrix (ECM) proteins or monoclonal antibodies (mAb) stimulates cytoskeletal rearrangement leading to cell spreading and respiratory burst. Tyrosin phosphorylation of a variety of proteins and activation of the Src family kinases within polymorphonuclear leukocytes (PMN) have recently been implicated in the intracellular signaling pathways generated by leukocyte integrins (Yan, S.R., L. Fumagalli, and G Berton. 1995. J. Inflammation. 45:217-311.) To directly test whether these functional responses are dependent on the Src family kinases p59/61hck and p58c-fgr, we examined adhesion-dependent respiratory burst in PMNs isolated from hck -/-, fgr -/-, and hck -/- fgr -/- knockout mice. Purified bone marrow PMNS from wild-type mice released significant amounts of O2- when adherent to fibrinogen-, fibronectin-, or collagen-coated surfaces, in the presence of activating agents such as tumor necrosis ...
A new study by Marieke Meijer (FGA) published in EMBO Journal reveals a novel pathway for neurons to shut down synaptic transmission via tyrosine phosphorylation of Munc18-1.
Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK (By similarity).
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases. Protein Tyrosine Kinase (PTK) family; C-terminal Src kinase (Csk) subfamily; catalytic (c) domain. The Csk subfamily is composed of Csk, Chk, and similar proteins. 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. Csk subfamily kinases are cytoplasmic (or nonreceptor) tyr kinases containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr ...
Yao, Q., B. Q. Liu, H. Li, D. McGarrigle, B. W. Xing, M. T. Zhou, Z. Wang, J. J. Zhang, X. Y. Huang and L. Guo (2014). "C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2." J Biol Chem 289(18): 12666-78 ...
Treatment with 10 completely M PP2 for 1 hour Constantly blocked ERK phosphorylation in these lymphoma cells au He LY3 OIC, one hour Higher dose of PP2 for completelys Full blocking SFK activity T requires. 1 to M PP1 that are not sufficient to reduce the activity to t SFK block is not inhibited ERK phosphorylation. In line so that the growth of cells is not inhibited UCS 2 at this dose. Because ERK MAPK kinases Src PAR is embroidered and asked if JNK MAPK is also embroidered controlled by the Src kinase. PP2 not affect the phosphorylation of JNK in CH12, LY3 tested UCS 2 and Ly10 lines and two B-lymphoma cells, suggesting that the JNK pathway is not controlled Controlled by Src kinase. Dasatinib and has not decreased in the phosphorylation of JNK UCS 2 cells. PI-3-kinase / AKT survival pathway is activated in a variety of important cancer cells. In B cells, CD19 Lyn phosphorylates to activate PI-3 kinase / AKT in response to antigenic stimulation.. ...
We previously reported that endogenous ROS production by high glucose in diabetic GK islets is elevated compared with that in control Wistar islets and is effectively ameliorated by Src inhibition, suggesting that Src may be activated in GK islets (6). In the present study, we first investigated whether Src activity is altered in GK islets. Immunoblotting analysis revealed that the level of Src pY416, which indicates the level of Src activation, is higher in GK islets than that in Wistar islets, despite lower levels of total Src, Src pY527, and Csk. The lower level of total Src seems to be a consequence of Src activation. Targeted degradation of active forms of Src is brought about by ubiquitination (29). The protooncogene c-Cbl, recently found to be an E3 ubiquitin ligase, mediates ubiquitination of activated Src (30). These reports suggest that increased degradation of activated Src may result in a lower level of total Src in GK islets. In addition, a lower level of Csk might cause a lower ...
摘 要:BCR/ABL融合蛋白是慢性粒细胞白血病(CML)的分子标志,具有高激酶活性,其在疾病发生、发展中扮演了极其重要的角色。伊马替尼(Imatinib)靶向抑制BCR-ABL,为CML慢性期的一线治疗药。BCR/ABL与Src家族激酶(Src-family kinases, SFK)之间也存在相互活化作用,通过激活众多信号通路,导致CML向急变期发展,并导致伊马替尼耐药。对有关BCR/ABL与SFK两者的相互作用机制及其生物学效应的研究进行总结 ...
The present invention relates to the treatment of EGFR-mediated disease, particularly cancer by inhibiting or blocking EGFR and src in combination or simultaneously. The invention relates to treatment, prevention, or modulation of cancer, particularly EGFR-mediated disease, with one or more EGFR modulator and src inhibitor in combination. The invention further relates to the treatment of cancer with anti-EGFR antibodies and src inhibitors. Methods and compositions for treatment of cancer with the antibody anti-EGFR mAb806 in combination or series with a src inhibitor or src inhibitors are described.
Complete information for SYF2 gene (Protein Coding), SYF2 Pre-MRNA Splicing Factor, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
TNBC has been thought as an extremely aggressive and refractory malignancy (29). Currently, no targeted drug is approved to use in the treatment of TNBC in clinic (30). Though some targeted drugs have entered clinical trials, most of them just showed very limited efficacy against TNBC. For example, dasatinib, a SRC family kinase inhibitor, has been assessed in phase II clinical trial. As a single agent, dasatinib exhibited moderate efficacy in TNBC patients and the clinical response rate was just 9.3% (4/43; ref. 31). Another agent, sorafenib, a VEGFR/Raf inhibitor, has been reported to have modest activity as a single agent in metastatic breast cancer patients, which contained some TNBC patients (32). Interestingly, a recent study has demonstrated that combined use of dasatinib and sorafenib displayed an enhanced efficacy compared with sole use of either dasatinib or sorafenib in inhibiting TNBC cells (33). This study prompted an advantage of use agents concurrently targeting multi-targets in ...
AZD0424 is a potent orally available, potent (IC50 approximately 4 nM) inhibitor of Src and ABL1 kinases with additional activity against Src family kinase (SFK) members including Yes and Lck. AZD0424 was selective for SFKs and ABL1 kinase over C-terminal Src kinase (a negative regulator of Src) and a range of other kinase targets. The anti-cancer activity of AZD0424 is thought to be mediated primarily by anti-migratory and anti-invasive signalling and, as such, it is expected that in the late stage cancer setting strong signals of efficacy with this compound used as a single agent are unlikely, requiring it to be administered in combination with other anti-cancer agents.. In summary the study will be performed in four main stages:. ...
Wang, Z., Han, Q. Q., Zhou, M. T., Chen, X., and Guo, L. (2016) Protein turnover analysis in Salmonella Typhimurium during infection by dynamic SILAC, Topograph, and quantitative proteomics. J. Basic Microbiol. 56, 801-811. Yao, Q., Liu, B. Q., Li, H., McGarrigle, D., Xing, B. W., Zhou, M. T., Wang, Z., Zhang, J. J., Huang, X. Y., and Guo, L. (2014) C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2. J. Biol. Chem. 289, 12666-12678. ...
The inhibition obtained by the number of molecules in 1 µg rCCP1-CCP2-SP per ml was. thus said to be equivalent to the number of molecules in 1·76 (79 247/45 073) µg MASP-1 per ml. We added the rCCP1-CCP2-SP to 10% fetal calf serum before performing the dilutions in order to obtain a similar matrix and to obtain comparable slopes of the dilution curve of the standard plasma and the recombinant material (the antibodies employed do not cross-react with bovine MASP-1). To test for the specificity of the assay, purified rMAp44 or rMASP-3 (produced and purified as described in Degn et al. [21]) was added to the MASP-1 assay at a concentration of 10 µg/ml for rMAp44 Erismodegib ic50 and 2·5 µg/ml for rMASP-3 at the highest concentration and dilutions thereof. The addition of rMAp44 or rMASP-3 did not influence the signal. To characterize the assay further and to study the association of MASP-1 with other serum components, serum was subjected to gel. permeation chromatography (GPC) on a 1 × 30 ...
Supplementary Materials10549_2017_4442_MOESM1_ESM. blotting, luciferase reporter assays, TUNEL assays, analysis of the gene, and ChIP assays. Results NSC35446.HCl inhibited proliferation and induced apoptosis in antiestrogen resistant LCC9, T47DCO, MCF-7/RR, and LY2 cells but not in ER-negative breast malignancy cell lines. (mRNA and protein expression in LCC9 cells. NSC35446.HCl also inhibited NF-B activity and expression of NF-B target genes. analysis of the promoter recognized nine estrogen response element (ERE) half-sites and one ERE-like full-site. ChIP assays revealed that ER was recruited to the ERE-like full-site and five from the nine half-sites which ER recruitment was inhibited by NSC35446.HCl in T47DCO and. ...
Complete information for FGR gene (Protein Coding), FGR Proto-Oncogene, Src Family Tyrosine Kinase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Considering these results, our failure to detect mutations in our cancer materials could mean that: (a) no c-src mutations were, in fact, present; and (b) activating genetic alterations had occurred in other regions of c-src outside exon 12 in the tumors we studied. According to the method described by Irby et al. (10) , the PCR products from tumor samples were sequenced manually, as well as by automated sequencers. In this method, there would be a possible risk for a technical artifact, such as artificial mutation, generated in the process of PCR amplification and for contamination.. c-src and structurally related members of the src family are non-receptor tyrosine kinases that reside within the cell, associated with cell membranes; they seem to transduce signals from transmembrane receptors to the cell interior (24) . Many intracellular pathways can be stimulated on src activation, inducing a variety of consequences including morphological changes and cell proliferation (25, 26, 27) . c-src ...
Structure of a large fragment of the c-Src tyrosine kinase shows that interactions among domains, stabilized by binding of the phosphorylated tail to the SH2 domain, lock the molecule in a conformation that simultaneously disrupts the kinase active site and sequesters the binding surfaces of the SH2 and SH3 domains. N lobe rotates 9 degress relative to its position in the cAPK Sidechain of Glu310 moves 12 A ...
CSK antibody [CSK-04] (c-src tyrosine kinase) for ICC/IF, IP, WB. Anti-CSK mAb (GTX14996) is tested in Human, Mouse samples. 100% Ab-Assurance.
Ellison, S., Mori, J., Barr, Alastair J. and Senis, Y.A. (2010) CD148 enhances platelet responsiveness to collagen by maintaining a pool of active Src family kinases. Journal of Thrombosis and Haemostasis, 8 (7). pp. 1575-1583. ISSN 1538-7933 ...
Mouse Monoclonal Anti-Lyn Antibody (LYN-01) [PerCP]. Validated: WB, ICC/IF, IP. Tested Reactivity: Human, Mouse, Rat. 100% Guaranteed.
LYN-1604 is a potential ULK1 agonist with IC50 of 1.66 μM against MDA-MB-231 cells and it binds to wild-type ULK1 with a binding affinity in the nanom... Quality confirmed by NMR & HPLC. See customer reviews, validations & product citations.
K05704 tyrosine-protein kinase Src [EC:2.7.10.2] , (RefSeq) SRC, ASV, SRC1, THC6, c-SRC, p60-Src; SRC proto-oncogene, non-receptor tyrosine ...
マウス・モノクローナル抗体 ab1890 交差種: Ms,Rat,Hu 適用: WB,IP,ICC,Flow Cyt,ICC/IF…Lyn抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
SRC3兔多克隆抗体(ab10313)可与人样本反应并经WB, IP实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
购买我们的重组人Src蛋白。Ab51424为有活性的全长蛋白,在大肠杆菌中生产并经过Functional Studies, SDS-PAGE实验验证。中国80%以上现货。
Malignant mesothelioma is an aggressive tumor arising from mesothelial cells of serous membranes. Src family kinases (SFKs) have a pivotal role in cell adhesion, proliferation, survival and apoptosis. Here, we examined the effect of SFK inhibitors in NCI-H2052, ACC-MESO-4 and NCI-H28 cells, mesothelioma cell lines and Met5A, a human non-malignant mesothelial cell line. We found that PP2, a selective SFK inhibitor, inhibited SFK activity and induced apoptosis mediated by caspase-8 in NCI-H28 but not Met5A, NCI-H2052 and ACC-MESO-4 cells. Src, Yes, Fyn and Lyn protein, which are members of the SFK, were expressed in these cell lines, whereas NCI-H28 cells were deficient in Fyn protein. Small interfering RNA (siRNA) targeting Fyn facilitated PP2-induced apoptosis mediated by caspase-8 in NCI-H2052 and ACC-MESO-4 cells. PP2 reduced Lyn protein levels and suppressed SFK activity in all mesothelioma cell lines. Lyn siRNA induced caspase-8 activation and apoptosis in NCI-H28 cells but not in NCI-H2052 ...
A recently developed stable isotope dilution liquid chromatography-multiple reaction/mass spectrometry method to quantify focal adhesion kinase (FAK) activation loop phosphorylation was used to study endogenous Src kinase activity. This revealed that bis-phosphorylated pTyr576/Tyr577-FAK was a biomarker of Src activity and inactivation in vitro and in cell culture. Mouse embryonic fibroblasts (MEFs) expressing endogenous Src family kinases contained 65% unmodified Tyr576/Tyr577, 33% mono-phosphorylated-pTyr576-FAK, and 6% bis-phosphorylated-pTyr576/pTyr577-FAK. In contrast, MEFs expressing oncogenic Y529FSrc contained 38% unmodified Tyr576/Tyr577-FAK, 29% mono-phosphorylated-pTyr576-FAK, and 19% bis-phosphorylated-pTyr576/pTyr577-FAK. This new method has made it possible to accurately determine the absolute amounts of FAK phosphorylation that occur after Src inhibition in cell culture and in vitro with increasing concentrations of the Src inhibitor ...
PAG (phosphoprotein associated with GEMs), also known as Cbp (Csk-binding protein), is a ubiquitously expressed 46 kDa transmembrane adaptor protein present in membrane rafts (glycosphingolipid-enriched microdomains), which however migrates on SDS PAGE gels anomalously as an 80 kDa molecule. Following tyrosine phosphorylation by Src family kinases, PAG binds and thereby activates the protein tyrosine kinase Csk, the major negative regulator of the Src family kinases. Signaling via the B-cell receptor in B cells or high affinity IgE receptor (FcepsilonRI) in mast cells leads to PAG increased tyrosine phosphorylation and Csk binding, while T cell receptor signaling causes PAG dephosphorylation, loss of Csk binding and increased activation of the protein tyrosine kinase Lck ...
PAG (phosphoprotein associated with GEMs), also known as Cbp (Csk-binding protein), is a ubiquitously expressed 46 kDa transmembrane adaptor protein present in membrane rafts (glycosphingolipid-enriched microdomains), which however migrates on SDS PAGE gels anomalously as an 80 kDa molecule. Following tyrosine phosphorylation by Src family kinases, PAG binds and thereby activates the protein tyrosine kinase Csk, the major negative regulator of the Src family kinases. Signaling via the B-cell receptor in B cells or high affinity IgE receptor (FcepsilonRI) in mast cells leads to PAG increased tyrosine phosphorylation and Csk binding, while T cell receptor signaling causes PAG dephosphorylation, loss of Csk binding and increased activation of the protein tyrosine kinase Lck ...
Spleen tyrosine kinase (Syk) is a key regulatory factor in the IgE-mediated allergic signal transduction pathway in mast cells and basophils. Syk is phosphorylated on a number of tyrosines following the binding of IgE/allergen complexes to FcɛRI receptors leading to initiation of inflammatory signaling via downstream enzymes and scaffolding proteins. We examined the kinases responsible for the phosphorylation of key Syk tyrosines in rat RBL-2H3 basophilic cells and bone marrow-derived mast cells (BMMCs). The phosphorylation of Syk tyrosine 346 was completely blocked by the novel Src family kinase inhibitor BIRA766, suggesting this tyrosine is a pure substrate for Src family kinases ...
NSCLC cell lines showed different activation of EGFR- and Src-dependent pathways and variable sensitivity to Src inhibitors. A kinase assay demonstrated that all the compounds are able to directly inhibit not only Src, but also EGFR TK variants. However, in cell lysates only saracatinib and bosutinib efficiently reduced EGFR activation, while dasatinib was the more effective agent in inhibiting Src TK. In EGFR-activating mutant, erlotinib sensitive cells, saracatinib and bosutinib showed anti-proliferative effects related to simultaneous EGFR/Src inhibition. In EGFR wt/Ras mutant cells Src inhibition by dasatinib interfered with cell proliferation and signal transduction. Since Src inhibitors had only moderate effects as single agents, both in vitro and in vivo, we tested the combination of saracatinib with EGFR inhibitors (erlotinib or cetuximab) in EGFR-addicted cells, and of dasatanib with MEK inhibitors (selumetinib) in Ras mutant, erlotinib resistant models. These combinations were ...
Iwasaki Y, Gay B, Wada K, Koizumi S (July 1998). "Association of the Src family tyrosine kinase Fyn with TrkB". Journal of ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ...
The N-terminus domain of LMP2A is tyrosine phosphorylated and associates with Src family protein tyrosine kinases (PTKs) as ... "An Epstein-Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases". Journal of ... In lymphoblastoid cell cultures, Syk tyrosine kinases have been found in LMP2A immunoprecipitates following in vitro kinase ... Tyrosine kinase LYN has also been detected in immunoprecipitates from transiently transfected B cells at residue Y112. ...
Cytoplasmic tyrosine kinases. Src-family, Syk-ZAP-70 family, and BTK family of tyrosine kinases, the Abl gene in CML - ... Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP ... Thomas SM, Brugge JS (1 November 1997). "Cellular functions regulated by Src family kinases". Annual Review of Cell and ... Summy JM, Gallick GE (December 2003). "Src family kinases in tumor progression and metastasis". Cancer Metastasis Reviews. 22 ( ...
... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ... protein kinase binding. • small GTPase binding. • Rac GTPase binding. Cellular component. • cytoplasm. • cell-cell junction. • ... The WASp family proteins includes WASp, N-WASp, SCAR/WAVE, WHAMM and WASH the five of them share a C- terminal VCA (verprolin, ... WASp is the founding member of a gene family which also includes the broadly expressed N-WASP (neuronal Wiskott-Aldrich ...
Src kinases[edit]. The Src-family kinases are examples of proteins that utilize autophosphorylation to sustain their activated ... Ataxia telangiectasia mutated kinase (ATM kinase)[edit]. ATM kinase, a member of the PI3-like family of serine/threonine ... The probable activation mechanism of src kinase in cancer is as follows: *1. The src kinase is kept in an inactive form through ... src-kinase deregulation can enhance tumor growth and invasive potential of cancer cells.[2] The activity of src kinases is ...
For example, in T cells, Lck and Fyn (Src family kinases) phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ... PLCG1 can be activated by receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases. For example, when activated, ... protein kinase binding. • phosphatidylinositol phospholipase C activity. Cellular component. • cytoplasm. • cytosol. • cell ...
Thomas SM, Brugge JS (1 November 1997). "Cellular functions regulated by Src family kinases". Annual Review of Cell and ... Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP ... Summy JM, Gallick GE (December 2003). "Src family kinases in tumor progression and metastasis". Cancer Metastasis Reviews. 22 ( ... Receptor tyrosine kinases add phosphate groups to other proteins to turn them on or off. Receptor kinases add phosphate groups ...
Thomas, S.M.; Brugge, J.S. (1997). "Cellular functions regulated by Src family kinases". Annu. Rev. Cell Dev. Biol. 13: 513-609 ... Tatosyan, A.G; Mizenina, O.A. (2000). "Kinases of the Src family: structure and functions". Biochemistry. 65 (1): 49-58. PMID ... clustering of integrins causes co-localization with caveolin-1 and activates non-receptor tyrosine kinases of the Src family ... By binding integrin α5β1 on endothelia cells it inhibits the signaling pathways of Ras and Raf kinases and decreases ERK-1 and ...
"Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors". The Journal ... 1-phosphatidylinositol-3-kinase regulator activity. • protein binding. • type B gastrin/cholecystokinin receptor binding. • ... regulation of phosphatidylinositol 3-kinase activity. • G-protein coupled receptor signaling pathway. • phospholipase C- ...
... is a member of the Src-family of kinases (SFK), the first proto-oncogene to be identified. The discovery of the Src-family ... This family also includes Abl, Src, focal adhesion kinase and Janus kinase.) Fyn is located downstream of several cell surface ... pharmacologic inhibitors of Src family kinases, such as PP2; note that PP2 also inhibits other tyrosine protein kinases such as ... "The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases". J. Biol. Chem. 276 (20): 17199-205. ...
It is a member of the Src family of tyrosine kinases. Lck is most commonly found in T cells. It associates with the cytoplasmic ... Zamoyska R, Basson A, Filby A, Legname G, Lovatt M, Seddon B (Feb 2003). "The influence of the src-family kinases, Lck and Fyn ... Palacios EH, Weiss A (Oct 2004). "Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation". ... 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". ...
This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein contains N-terminal sites for ... Tatosyan AG, Mizenina OA (Jan 2000). "Kinases of the Src family: structure and functions". Biochemistry. Biokhimii͡A. 65 (1): ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/S0960-9822(02)00642 ... Resh MD (Feb 1994). "Myristylation and palmitylation of Src family members: the fats of the matter". Cell. 76 (3): 411-3. doi: ...
The abbreviation Lyn is derived from Lck/Yes novel tyrosine kinase, Lck and Yes also being members of the Src kinase family. ... Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (Apr 2002). "Phosphatidylinositol 3-kinase and Src family kinases are ... "Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein". Proceedings ... Tyrosine-protein kinase Lyn is a protein that in humans is encoded in humans by the LYN gene. Lyn is a member of the Src family ...
"Autophosphorylation activity and association with Src family kinase of Sky receptor tyrosine kinase". Biochem. Biophys. Res. ... 1993). "Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor". EMBO J. 12 ( ... The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity ... Non-receptor type protein-tyrosine kinases closely related to src and yes compose a multigene family". Int. Symp. Princess ...
Nihalani D, Wong H, Verma R, Holzman LB (April 2007). "Src family kinases directly regulate JIP1 module dynamics and activation ... Stress-activated protein kinase kinase 4 (SAPK kinase 4, SAPKK4) c-Jun N-terminal kinase kinase 2 (JNK kinase 2, JNKK2) Stress- ... Dual specificity mitogen-activated protein kinase kinase 7, also known as MAP kinase kinase 7 or MKK7, is an enzyme that in ... and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2, ...
Reelin modulates NMDA function through Src family kinases and DAB1. significantly enhancing LTP in the hippocampus. Src kinase ... Yu XM, Askalan R, Keil GJ, Salter MW (January 1997). "NMDA channel regulation by channel-associated protein tyrosine kinase Src ... A related gene family of NR3 A and B subunits have an inhibitory effect on receptor activity. Multiple receptor isoforms with ... Neuroscience portal Calcium/calmodulin-dependent protein kinases Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (1997). " ...
Csk may then suppress the Src-family kinases through phosphorylation. B cell antigen receptor (BCR) is a complex between a ... After that, Syk family tyrosine kinases bind these phosphotyrosine residues of ITAMs to initiate the signaling cascade. Syk can ... This crosslinking, similar to IgE signaling, then recruit doubly acylated non-receptor Src-like tyrosine kinases to ... This crosslinking then recruits doubly acylated non-receptor Src-like tyrosine kinase Lyn to phosphorylate ITAMs. ...
"Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases". Kidney Int. 64 (2): 404-13. doi:10.1046/j.1523- ...
... and Src family kinases". The Journal of Biological Chemistry. 271 (52): 33525-30. doi:10.1074/jbc.271.52.33525. PMID 8969217. ... Kitayama C, Uyeda TQ (February 2003). "ForC, a novel type of formin family protein lacking an FH1 domain, is involved in ... Chalkia D, Nikolaidis N, Makalowski W, Klein J, Nei M (December 2008). "Origins and evolution of the formin multigene family ... Src homology 3) domain proteins, and WW domain proteins. The actin nucleation-promoting activity of S. cerevisiae formins has ...
"Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases". Nature. 404 (6781): 999-1003. doi: ... Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW (May 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/ ... Yamaguchi Y, Wada T, Suzuki F, Takagi T, Hasegawa J, Handa H (August 1998). "Casein kinase II interacts with the bZIP domains ... Kim J, Jia L, Stallcup MR, Coetzee GA (February 2005). "The role of protein kinase A pathway and cAMP responsive element- ...
February 9, 1996). "Activation of Btk by a phosphorylation mechanism initiated by src family kinases". Science. 271 (5250): 822 ... His discovery of the tyrosine kinase activity in the ABL1 protein and the demonstration of the BCR-ABL oncoproteins in ... Witte also co-discovered the gene for Bruton's tyrosine kinase, a protein essential for normal B-lymphocyte development that, ... David Baltimore (MIT; 1976 to 1980). 1990 Milken Family Medical Foundation Award in Basic Cancer Research 1991 Richard and ...
"Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP- ... "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src ... "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src ...
Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (Apr 2002). "Phosphatidylinositol 3-kinase and Src family kinases are ... "Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases". Science. 271 (5250): 822-5. doi:10.1126/ ... Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, ... Yang WC, Collette Y, Nunès JA, Olive D (Apr 2000). "Tec kinases: a family with multiple roles in immunity". Immunity. 12 (4): ...
The protein encoded by this gene belongs to the src family kinases. This protein is similar to the src kinase associated ... "Entrez Gene: SKAP2 src kinase associated phosphoprotein 2". Alenghat FJ, Baca QJ, Rubin NT, Pao LI, Matozaki T, Lowell CA, ... Src kinase-associated phosphoprotein 2 is an enzyme that in humans is encoded by the SKAP2 gene. ... "RA70 is a src kinase-associated protein expressed ubiquitously". Biochemical and Biophysical Research Communications. 252 (3): ...
"Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP- ...
It belongs to the tyrosine kinase inhibitor family of medications.[4] It is taken by mouth.[4] ... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth ... Minkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors ...
Culbreth, M., Zhang, Z., & Aschner, M. (2017). Methylmercury augments Nrf2 activity by downregulation of the Src family kinase ... Culbreth, M, Zhang, Z & Aschner, M 2017, Methylmercury augments Nrf2 activity by downregulation of the Src family kinase Fyn ... Methylmercury augments Nrf2 activity by downregulation of the Src family kinase Fyn. / Culbreth, Megan; Zhang, Ziyan; Aschner, ... Methylmercury augments Nrf2 activity by downregulation of the Src family kinase Fyn. NeuroToxicology. 2017 Sep 1;62:200-206. ...
Focal Adhesion Kinase 2); EC 2.7.10.2 (src-Family Kinases); EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 3 ... Inhibition of BCR/Src signaling in CLL cells induced their apoptosis, indicating that these findings are linked causally. These ... Other members of the R3-PTP family (DEP-1, GLEPP1 and SAP-1) also exhibited the potential to interact with VE-cadherin. The ... Tie2 is a tyrosine kinase receptor located predominantly on vascular endothelial cells that plays a central role in vascular ...
Src family protein tyrosine kinases are activated following engagement of many different classes of cellular receptors and ... This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms ... Cellular functions regulated by Src family kinases.. Thomas SM1, Brugge JS. ... While several of these kinases have evolved to play distinct roles in specific receptor pathways, there is considerable ...
GPCRs Signaling Directly Through Src-Family Kinases Message Subject. (Your Name) has forwarded a page to you from Science ... Here, we discuss the evidence for direct interaction and activation of Src-family kinases by GPCRs and data that suggest that ... Several GPCRs directly interact with Src-family kinases. ... GPCRs Signaling Directly Through Src-Family Kinases. *Deirdre ... AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have ...
Members of the Src family show interactions between protein domains that are thought to control kinase activity. In fact, the ... Thus, Unc119 may represent a new class of regulatory protein for Src family kinases. ... Members of the Src familiy of protein kinases contribute to signals emanating from various receptors on the cell membrane, but ... Now Cen et al. have discovered a new activator of Src-like kinases, Unc119, that appears to work in a similar manner. Unc119 ...
... and the Src family kinase Fyn. Blockers of Src family kinases inhibited FAK phosphorylation and axon outgrowth and attraction ... Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.. Liu G1, Beggs H, Jürgensen C, ... f) An immune complex kinase assay for Src family kinases showed that Fyn was activated by purified human netrin-1. Cortical ... Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction ...
Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the ... a tyrosine kinase domain, and C-terminal tail. Src family kinases interact with many cellular cytosolic, nuclear and membrane ... Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker ... Zhang S, Yu D (March 2012). "Targeting Src family kinases in anti-cancer therapies: turning promise into triumph". Trends in ...
... activation of the p72syk tyrosine kinase and formation of protein complexes containing p72syk and Src family kinases in ... Whereas Src family and Syk tyrosine kinases play an important role in various classical functions of neutrophils, such as ... Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils. Thornin Ear, Olga ... H. Möhn, V. Le Cabec, S. Fischer, and I. Maridonneau-Parini, "The src-family protein-tyrosine kinase p59hck is located on the ...
Buy An integrative dynamic systems approach to understanding Src family kinase signalling by Hendrik Fuß (Paperback) online at ... A further study addressed issues relating to the interface between Src family kinases and several receptor tyrosine kinases. ... An integrative dynamic systems approach to understanding Src family kinase signalling By Hendrik Fuß ... The model serves as a coherent and quantifiable description of Src family kinase signalling events and makes novel, ...
Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity. Pat Manzerra, M. ... Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity ... Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity ... Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity ...
... p60-Src; SRC; SRC1 In 1911, pathologist Francis Peyton Rous isolated a virus from a Plymouth Rock chicken that has continued to ... Src family kinase inhibitors in cancer therapy. In: Georgiev B, Markovski S, editors. Serpins and protein kinase inhibitors: ... Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 2003;22(4):337-58.PubMedCrossRefGoogle Scholar ... Regulation of Src family kinases in human cancers. J Signal Transduct. 2011;1-14.CrossRefGoogle Scholar ...
Activation of BTK by a Phosphorylation Mechanism Initiated by SRC Family Kinases ... Activation of BTK by a Phosphorylation Mechanism Initiated by SRC Family Kinases ... Activation of BTK by a Phosphorylation Mechanism Initiated by SRC Family Kinases ... Activation of BTK by a Phosphorylation Mechanism Initiated by SRC Family Kinases ...
The Src family of protein tyrosine kinases includes Src, Lck, and Lyn. To investigate which Src-family kinase is activated in ... were cut in a cryostat and processed for phosphorylated-Src family (Tyr416; p-Src family), p-Src, p-Lck, p-Lyn, p-ERK1/2, p-p38 ... Src and other Src-family kinases (SFKs) are expressed widely throughout the mammalian CNS and have been implicated in ... Marked activation of Src family in the spinal dorsal horn after L5 spinal nerve injury. A, E, p-Src family immunostaining in ...
Src-family kinases are not required for C. trachomatis attachment or entry.The role of Src-family kinases at various stages of ... muridarum in cells deficient in Src-family kinases is unknown, one hypothesis might be that Src-family kinases play a role in a ... appear to be growth restricted by the activities of Src-family kinases. Depletion of Src-family kinases triggers a more rapid ... exhibit unique requirements for Src-family kinases throughout their developmental cycle. Utilization of Src-family kinases by C ...
Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species. Jeffrey Mital, Ted Hackstadt ... Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species Message Subject (Your Name) has forwarded a ... Diverse requirements for Src-family tyrosine kinases distinguish chlamydial species. mBio 2(2):e00031-11. doi:10.1128/mBio. ...
... p38MAPK and Erk1/2 kinases. Here, we found that Src family kinases were upstream of these kinases and played a central role in ... These findings indicated that Src family kinases mediate monocyte survival through the regulation of receptor phosphorylation ... Thus, we predict that targeting Src family kinases may have therapeutic implication in inflammatory diseases. ... We observed that M-CSF promoted c-Src activation in monocytes and MDMs in a time-dependent manner. Src inhibitors reduced M-CSF ...
We examined the role of Src-family kinases (SFKs) in vivo. Electroporation of kinase-inactive Src constructs into soleus ... Such dominant-negative Src constructs interfere with many members of the Src family (e.g., Src, Fyn, and Yes), not just Src ... We first used a kinase-inactive Src expression construct, Src-AM, in this approach. Src-AM harbors two mutations, K295M and ... Thomas SM, Brugge JS (1997) Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13: 513-609. ...
Overexpression of src family gene for tyrosine-kinase p59fyn in CD4-CD8- T cells of mice with a lymphoproliferative disorder. ... Overexpression of src family gene for tyrosine-kinase p59fyn in CD4-CD8- T cells of mice with a lymphoproliferative disorder ... Overexpression of src family gene for tyrosine-kinase p59fyn in CD4-CD8- T cells of mice with a lymphoproliferative disorder ... Overexpression of src family gene for tyrosine-kinase p59fyn in CD4-CD8- T cells of mice with a lymphoproliferative disorder ...
VEGF165-induced vascular permeability requires NRP1 for ABL-mediated SRC family kinase activation. Alessandro Fantin, Anastasia ... VEGF165-induced vascular permeability requires NRP1 for ABL-mediated SRC family kinase activation ...
The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn. Blood 110: 2511- ... Src family kinases (SFK) are critical for initiating and regulating the response of mast cells activated by engagement of the ... A Minor Catalytic Activity of Src Family Kinases Is Sufficient for Maximal Activation of Mast Cells via the High-Affinity IgE ... A Minor Catalytic Activity of Src Family Kinases Is Sufficient for Maximal Activation of Mast Cells via the High-Affinity IgE ...
The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. Lck catalyzes the initial ... The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. Lck catalyzes the initial ... STRUCTURAL ANALYSIS OF THE LYMPHOCYTE-SPECIFIC KINASE LCK IN COMPLEX WITH NON-SELECTIVE AND SRC FAMILY SELECTIVE KINASE ... Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase ...
... Oncogene. 1993 Nov;8(11):3133-9. ... The 55-kDa molecule phosphorylated by diamide turned out to be a src family protein tyrosine kinase, p56lck. The immune complex ... kinase assay showed that the kinase activity of p56lck of diamide-treated PBL blasts was enhanced. The tryptic peptide mapping ... the tyrosine phosphorylation and presumably kinase activity of p56lck were swiftly enhanced by oxidative stress, indicating ...
The Src family kinases Hck and Fgr regulate neutrophil responses to N-formyl-methionyl-leucyl-phenylalanine. J Immunol. 2007; ... The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a ... Src family kinases (SFK) are the central players in the outside-in signaling process, assigning them a critical role for proper ... Deficiency of src family kinases p59/61hck and p58c-fgr results in defective adhesion-dependent neutrophil functions. J Cell ...
Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae.. A M Shenoy-Scaria, D J ... Recent work has demonstrated that p56lck, a member of the Src family of protein tyrosine kinases (PTKs), is modified by ... Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. ... in addition to amino-terminal myristoylation that is a common modification of the Src family of PTKs). This is now extended to ...
... we investigated the role of Src family kinases. Blockade of Src family kinases using an Src-specific tyrosine kinase inhibitor ... EGF and GRP can activate Src family kinases. Although EGF activates Src family kinases by direct interaction between Src and ... Src Family Kinases Regulate EGFR and MAPK Activation by GRP in HNSCC Cells.. Src family kinases have been implicated in the ... Src family kinases also mediate EGFR and MAPK activation by GRP. Therefore, we hypothesized that Src family kinases contribute ...
  • Culbreth, M , Zhang, Z & Aschner, M 2017, ' Methylmercury augments Nrf2 activity by downregulation of the Src family kinase Fyn ', NeuroToxicology , vol. 62, pp. 200-206. (elsevier.com)
  • In today's study, FYN kinase manifestation was connected with neuroendocrine biomarkers in PCa cell PCa and lines liver organ metastasis derived cells. (exposed-skin-care.net)
  • Physique 1 FYN kinase co-expressed with neuroendocrine biomarkers in primary PCa with neuroendocrine phenotype and in PCa liver metastasis FYN expression is associated with NE marker appearance in PCa We following analyzed whether FYN appearance was connected with NE tumor marker appearance lines cataloged in the Tumor Cell Range Encyclopedia (CCLE, http://www.broadinstitute.org/ccle). (exposed-skin-care.net)
  • The Src kinase pathway has emerged as a major player in cancer progression, especially relating to metastasis. (aacrjournals.org)
  • Of the 9 SFK members, c-Src, Fyn, and Yes are most widely expressed, and c-Src itself has been most frequently implicated in tumorigenesis and metastasis ( 11 ). (aacrjournals.org)
  • In 1976, Bishop and Varmus demonstrated that the v-Src gene has a normal cellular homolog gene (protooncogene), c-Src , and that the v-Src gene product, pp60v-Src or v-Src, is a phosphoprotein with an apparent molecular mass of 60 kDa with intrinsic protein kinase activity (Stehelin et al. (springer.com)
  • Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity . (genecards.org)
  • FYN is a SRC family kinase (SFK) that is been shown to be up-regulated in human being prostate tumor (PCa) cells and cell lines. (exposed-skin-care.net)
  • Src-family kinase (SFK) signaling impacts multiple tumor-related properties, particularly in the context of the brain tumor glioblastoma. (elsevier.com)
  • The elevated c-Src levels have also been shown to have a correlation with advanced stages of the tumor, size of tumor, and metastatic potential of tumors. (wikipedia.org)
  • We recently showed that the Src target, FAK, is overexpressed and phosphorylated in patient thyroid tumor samples, providing justification to pursue this pathway as a clinically relevant target. (aacrjournals.org)
  • c-Src has been shown to play an important role in regulating osteoclast function and tumor colonization to the bone, making Src an attractive therapeutic target for the prevention and treatment of bone metastases ( 12, 13 ). (aacrjournals.org)
  • Rous sarcoma virus is the archetypal retrovirus, capable of causing tumors in chickens and rapidly transforming cells in culture with high efficiency through production of the protein viral sarcoma (v-Src), the first identified transforming protein. (springer.com)
  • Src, Yes, and Fyn are ubiquitously expressed, with some functional redundancy, whereas the other family members are expressed in subsets of specialized cells. (asm.org)
  • The functional implications of these phenotypes are supported by the observation that chlamydial species that do not recruit Src-family kinases to their inclusion membranes ( 16 ) do not traffic to the MTOC and show enhanced inclusion development in cells deficient in Src-family kinases. (asm.org)
  • Src family kinases (SFK) are critical for initiating and regulating the response of mast cells activated by engagement of the high-affinity IgE receptor, FcεRI. (jimmunol.org)
  • Restoration of wild-type and WeeB lyn alleles in lyn −/− cells generated activation phenotypes similar to those in nontransduced wild-type and WeeB cells, respectively, whereas a kinase-dead allele resulted in a phenotype similar to that of empty-vector-transduced cells. (jimmunol.org)
  • GRP also failed to induce MAPK activation in dominant-negative c-Src-transfected HNSCC cells. (aacrjournals.org)
  • Invasion and growth assays showed that c-Src was required for GRP-induced proliferation or invasion of HNSCC cells. (aacrjournals.org)
  • neuroendocrine differentiation occurring in PCa cells can be, at least partly, controlled by FYN kinase. (exposed-skin-care.net)
  • Another Btk family kinase, Itk, which is expressed in T cells, is tyrosine phosphorylated and activated by engagement of either the T-cell receptor (TCR) or CD28 in T-cell lines and by FcɛRII stimulation in mast cells ( 1 , 6 , 16 ). (asm.org)
  • In this project we obtained the results showing that negative regulation by CD45 was observed in all B cells tested (WEHI-231,BAL-17,and splenic B cells) and that about 5% of total CD45 was constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibited Src-PTKs by dephosphorylating both the negative and the positive regulatory sites. (nii.ac.jp)
  • Overexpression of a constitutively active form of PI 3-kinase induced the phosphorylation of DAPP1 in unstimulated cells. (biochemj.org)
  • In the orthotopic xenograft model, mice implanted with non-target or Src or Fyn knockdown cells showed no differences in survival. (elsevier.com)
  • The requirement of the Src-PTK to induce tyrosine phosphorylation and activation of Syk was also demonstrated by cotransfection of syk and src-PTK cDNAs into COS cells. (rupress.org)
  • The c-Src:FAK complex plays a major role in the migration and invasion of both normal and cancer cells, making it an attractive target for drug discovery. (pitt.edu)
  • Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. (oncotarget.com)
  • Src, Yes, Fyn and Lyn protein, which are members of the SFK, were expressed in these cell lines, whereas NCI-H28 cells were deficient in Fyn protein. (oup.com)
  • Src, Fyn and Yes are expressed ubiquitously in all cell types while the others are generally found in hematopoietic cells. (wikipedia.org)
  • Immunoblotting showed that c-Src and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant SFK activated. (aacrjournals.org)
  • Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. (genecards.org)
  • Gandotinib Osteoclasts Fyn Src family kinase (SFK) M-CSF RANK ligand OCs are multinucleated hematopoietic cells with the unique capacity to degrade bone. (stopvivisection.info)
  • The GDNF-induced branching of MDCK cells requires Src activation, whereas the HGF-induced branching does not. (sigmaaldrich.com)
  • Deficiency of Src family kinases compromises the repopulating ability of hematopoietic stem cells. (iu.edu)
  • Drawing on recently published and unpublished work on the TCR and, in particular, the extensive literature on the regulation of Src kinases, in this Opinion article we discuss how TCR phosphorylation might be controlled in T cells. (frontiersin.org)
  • Tyrosine kinase LYN has also been detected in immunoprecipitates from transiently transfected B cells at residue Y112. (wikipedia.org)
  • Tie2 is a tyrosine kinase receptor located predominantly on vascular endothelial cells that plays a central role in vascular stability. (bireme.br)
  • Deficiency of Src family kinases p59/61hck and p58c-fgr results in defective adhesion-dependent neutrophil functions. (rupress.org)
  • In lymphoblastoid cell cultures, Syk tyrosine kinases have been found in LMP2A immunoprecipitates following in vitro kinase reactions followed by Syk antibody reimunnoprecipitation. (wikipedia.org)
  • Nonhuman chlamydial species C. caviae and C. muridarum show none of these requirements and, instead, appear to be growth restricted by the activities of Src-family kinases. (asm.org)
  • In culture, Src, Fyn, and Yes knockdown generally reduced growth and migration and altered motility-related phosphorylation patterns while Lyn knockdown did so to a lesser extent. (elsevier.com)
  • BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor . (wikipedia.org)