Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Mitogens: Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)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.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.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.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.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.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.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.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.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)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.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.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.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.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.Mitogen-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.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 184.108.40.206.Amino 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.PhosphoproteinsPyrimidines: 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.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.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.p38 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.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.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.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 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.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.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.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).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.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.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.fms-Like Tyrosine Kinase 3: A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.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.Kinetics: The rate dynamics in chemical or physical systems.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.Benzamides: BENZOIC ACID amides.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.Tyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.PiperazinesBlotting, 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.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.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.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.Cell Line, Tumor: A cell line derived from cultured tumor cells.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 enzymesRecombinant 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.Pokeweed Mitogens: Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.QuinazolinesProtein 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.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.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.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.Concanavalin A: A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.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.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.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.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).Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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.Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.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.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.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.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.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.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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Proto-Oncogene Proteins c-met: Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.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.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.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.Lactams, Macrocyclic: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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 220.127.116.11), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.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.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Phytohemagglutinins: Mucoproteins isolated from the kidney bean (Phaseolus vulgaris); some of them are mitogenic to lymphocytes, others agglutinate all or certain types of erythrocytes or lymphocytes. They are used mainly in the study of immune mechanisms and in cell culture.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.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 18.104.22.168.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.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 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.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.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.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.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.TYK2 Kinase: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.Protein Tyrosine Phosphatase, Non-Receptor Type 1: A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.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.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).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.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.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 22.214.171.124.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Isoflavones: 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.Cell 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.Janus Kinase 1: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.Cell Adhesion: Adherence of cells to surfaces or to other cells.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.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.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.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.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.Janus Kinase 3: A Janus kinase subtype that is predominantly expressed in hematopoietic cell. It is involved in signaling from a broad variety of CYTOKINE RECEPTORS including ones that utilize the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT.Cell 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.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.Oncogene Proteins v-abl: Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Mice, Inbred C57BLDNA 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.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.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)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.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.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.Receptor, trkA: A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.Proto-Oncogene Proteins c-hck: Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.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.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).Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Proto-Oncogene Proteins c-ret: Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 126.96.36.199.Receptor, erbB-2: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.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.MorpholinesChromonesElectrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Ligands: 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)Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.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.Shc Signaling Adaptor Proteins: A family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.Phosphoserine: The phosphoric acid ester of serine.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Molecular Weight: The sum of the weight of all the atoms in a molecule.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.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.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Receptor, Platelet-Derived Growth Factor beta: A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.TOR Serine-Threonine Kinases: A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.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.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
"Protein tyrosine phosphatase epsilon inhibits signaling by mitogen-activated protein kinases". Mol. Cancer Res. 1 (7): 541-50. ... "Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase ... Receptor-type tyrosine-protein phosphatase epsilon is an enzyme that in humans is encoded by the PTPRE gene. The protein ... "Entrez Gene: PTPRE protein tyrosine phosphatase, receptor type, E". Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A ...
"Interaction of mitogen-activated protein kinases with the kinase interaction motif of the tyrosine phosphatase PTP-SL provides ... Ogata M, Oh-hora M, Kosugi A, Hamaoka T (1999). "Inactivation of mitogen-activated protein kinases by a mammalian tyrosine- ... "A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine ... "PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ...
1994). "Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1". Nature. 367 (6464): 651-4 ... They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are ... cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine ... 1993). "PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase". Science. 259 (5102): 1763-6. doi:10.1126/science. ...
... a tyrosine kinase that initiates the JAK-STAT pathway. Activation also results in the activation of mitogen-activated protein ... kinases and Src kinase. Human prolactin receptors are insensitive to mouse prolactin. Prolactin levels may be checked as part ... This results in the activation of Janus kinase 2, ...
"Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. ... "Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. ... "Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase". Nat. Cell Biol. 1 (5): 305-11. ... "Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase". Nat. Cell Biol. 1 (5): 305-11. ...
"Tumor necrosis factor-induced activation and increased tyrosine phosphorylation of mitogen-activated protein (MAP) kinase in ...
MEK is a serine/tyrosine/threonine kinase. In the technical sense, RAF, MEK, and MAPK are all mitogen-activated kinases, as is ... 2001). "Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade". Recent Progress in Hormone ... "mitogen-activated protein kinase" (MAPK). The series of kinases from RAF to MEK to MAPK is an example of a protein kinase ... Activated Ras activates the protein kinase activity of RAF kinase. RAF kinase phosphorylates and activates MEK (MEK1 and MEK2 ...
... of Mycobacterium tuberculosisPromotes Protein Tyrosine Dephosphorylation and Inhibition of Mitogen-activated Protein Kinase in ... ManLAM is able to activate the serine/threonine kinase Akt via phosphorylation which is then able to phosphorylate Bad. ... ManLAM is thought to inhibit the IL-1 receptor-associated kinase (IRAK)-TRAF6 interaction, IκB-α phosphorylation, and nuclear ... By activating a phosphatase, LAM can inhibit LPS and IFN-γ induced protein tyrosine phosphorylation in monocytes. This ...
"T cell activation through the CD43 molecule leads to Vav tyrosine phosphorylation and mitogen-activated protein kinase pathway ...
"Stimulation of the mitogen-activated protein kinase cascade and tyrosine phosphorylation of the epidermal growth factor ...
... cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine ... "Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the ... "Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma". International Journal ... "Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated ...
... cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 ( ... a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase ... Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol ...
"Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase ... "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16 ... "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16 ... Lim YP, Low BC, Lim J, Wong ES, Guy GR (July 1999). "Association of atypical protein kinase C isotypes with the docker protein ...
Which forms functional intracellular tyrosine kinases. ErbB2 has no known binding ligand and absent of an active kinase domain ... The RAS pathway can couple with the mitogen-activated protein kinase pathway or a number of other possible effectors. The PI3K/ ... that activates the further process of transphosphorylation of the specific tyrosine kinases in the kinase domain of ErbB's ... share each other's active domains to activate transphosphorylation of the tyrosine kinases. The specific tyrosine molecules ...
1997). "Cripto enhances the tyrosine phosphorylation of Shc and activates mitogen-activated protein kinase (MAPK) in mammary ... 1999). "Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in ...
"Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". The ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... Nemoto S, Sheng Z, Lin A (Jun 1998). "Opposing effects of Jun kinase and p38 mitogen-activated protein kinases on cardiomyocyte ... "Mitogen-activated protein kinase 14". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). "Entrez Gene: MAPK14 mitogen- ...
... interact with Galphaq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase ...
"Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. ... "Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase". Nat. Cell Biol. 1 (5): 305-11. ... Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene. The protein encoded by this gene ... "Entrez Gene: MAPK3 mitogen-activated protein kinase 3". Buggele WA, Johnson KE, Horvath CM (2012). "Influenza A virus infection ...
... non-receptor tyrosine kinase originally identified as a substrate for the oncogene protein tyrosine kinase v-src. This ... cytosolic kinase has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. ... PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by ... Lineage for Protein: Focal adhesion kinase 1 Q00944 "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". Guan JL, Shalloway D ( ...
... c-src kinase, tyrosine kinase 2 mitogen-activated protein kinase kinase, tyrosine kinase 2, c-jun, JNK1, Janus kinase 1, TNF-a ...
The ERK2 mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many ... At any point in this process, the β-arrestins may also recruit other proteins-such as the non-receptor tyrosine kinase (nRTK), ... receptor domain by protein kinases. Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain ... The presence of a tyrosine-phosphorylated ITIM (immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is ...
... a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". J ... DUSP7 belongs to a class of DUSPs, designated MKPs, that dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK, ... DUSPs are characterized by their ability to de-phosphorylate both tyrosine (EC 188.8.131.52) and serine / threonine (EC 184.108.40.206) ... 1996). "Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase". ...
... a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". ... a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". ... "Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and ... Saha M, Skopelja S, Martinez E, Alvarez DL, Liponis BS, Romero-Sandoval EA (Oct 2013). "Spinal mitogen-activated protein kinase ...
Guan has made seminal contributions in the fields of protein tyrosine phosphatase, Mitogen-Activated Protein (MAP) kinase, and ... In contrast, TORC2 phosphorylates and activates AKT, a key kinase involved in cell growth and apoptosis. Guan and his team are ... In addition, they are studying the mechanism of mTOR activation by the phosphatidyl inositol 3-kinase (PI3K). The second ... For example, TORC1 phosphorylates the ribosomal S6 kinase (S6K), thereby regulating translation and cell growth. ...
"Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. ... "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 ( ... The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to ... "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. 16 (8): 1909-20. doi:10.1093/ ...
The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB). The PDGF family also ... PDGF is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In ... The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of ... receptor tyrosine kinases". EMBO J. 15 (2): 290-298. doi:10.1002/j.1460-2075.1996.tb00359.x. PMC 449944. PMID 8617204.. ...
Hypertonic shock induces the activation of mitogen-activated protein kinases and the expression of a defined set of genes, ... and inhibition of HER tyrosine kinase activity. Inhibition of HER activation interferes with the hypertonic induction of two ... Hypertonic shock induces the activation of mitogen-activated protein kinases and the expression of a defined set of genes, ... Hypertonic shock induces the activation of mitogen-activated protein kinases and the expression of a defined set of genes, ...
198 Involvement of Mitogen Activated Kinase Kinase 7 in Tyrosine Kinase Inhibitor Induced Myocardial Injury ... 198 Involvement of Mitogen Activated Kinase Kinase 7 in Tyrosine Kinase Inhibitor Induced Myocardial Injury ... Mitogen activated kinase kinase 7 (MKK7) is a selective upstream regulator of the c-Jun N-terminal kinase (JNK) pathway. ... Introduction Mitogen Activated Protein (MAP) kinase signalling cascades play significant roles in the development of cardiac ...
The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ... The Involvement of Tyrosine Kinases, Cyclic AMP/Protein Kinase A, and p38 Mitogen-Activated Protein Kinase in IL-13-Mediated ...
Downregulation of the Ras-Mitogen-Activated Protein Kinase Pathway by the EphB2 Receptor Tyrosine Kinase Is Required for Ephrin ... Downregulation of the Ras-Mitogen-Activated Protein Kinase Pathway by the EphB2 Receptor Tyrosine Kinase Is Required for Ephrin ... Downregulation of the Ras-Mitogen-Activated Protein Kinase Pathway by the EphB2 Receptor Tyrosine Kinase Is Required for Ephrin ... Downregulation of the Ras-Mitogen-Activated Protein Kinase Pathway by the EphB2 Receptor Tyrosine Kinase Is Required for Ephrin ...
Genistein is a broad-spectrum tyrosine kinase inhibitor that blocks both receptor and nonreceptor protein tyrosine kinases (6, ... tyrosine kinase(s), and MAPK to BFT-stimulated IL-8 production.To evaluate the interrelationship of the NF-κB, tyrosine kinase ... and the tyrosine kinase inhibitors genistein (broad-spectrum tyrosine kinase inhibitor; Sigma), PP2 (selective Src-family ... Induces Intestinal Epithelial Cell Secretion of Interleukin-8 through Mitogen-Activated Protein Kinases and a Tyrosine Kinase- ...
... serve as targets for H2O2 and this may be associated with the regulation of mitogen-activated protein (MAP) kinase activity in ... PTPs play a role in MAP kinase regulation. The activation of MAP kinases requires phosphorylation of Thr and Tyr res* ... Although Ser/Thr and Tyr kinases/phosphatases play a critical role in cell growth and development in animals, none of the ... is involved in the regulation of MAP kinase activities in plant cells (for review, see Tena et al., 2001; Zhang and Klessig, ...
... an effect mediated by tyrosine kinase/mitogen-activated protein kinase (MAPK) pathways. Estrogen also stimulates tyrosine ... Thus, estrogen, by activating an src tyrosine kinase and the extracellular signal-related protein kinase/MAPK signaling pathway ... phosphorylation of NMDA receptors via an src tyrosine kinase/MAPK pathway. Finally, estrogen-mediated enhancement of long-term ... potentiation in hippocampal slices is mediated by activation of an src tyrosine kinase pathway. ...
Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer cultures ... Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer cultures ... Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer cultures ... title = "Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer ...
Kinase/Protein Kinase B/Mitogen-Activated Protein Kinase Signaling after Growth Arrest-Specific Protein 6/Mer Receptor Tyrosine ... Kinase/Protein Kinase B/Mitogen-Activated Protein Kinase Signaling after Growth Arrest-Specific Protein 6/Mer Receptor Tyrosine ... The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal- ... mitogen-activated protein. Mer. Mer receptor tyrosine kinase. M-MLV. Moloney murine leukemia virus. PD 98059. 2-(2-amino-3- ...
Tyrosine Kinase Inhibitor, In Asian Patients With Advanced Non-Small-Cell Lung Cancer, Urothelial Cancer, Gastric Cancer, ... Tyrosine Kinase Inhibitor, In Asian Participants With Advanced Non-Small-Cell Lung Cancer, Urothelial Cancer, Esophageal Cancer ...
3 Mitogen-activated Protein (MAP)- One Important Class of Cytoplasmic Kinases. *4 How Receptor Tyrosine Kinases are De- ... How Receptor Tyrosine Kinases are Activated. Receptor tyrosine kinases is a transmembrane structure that anchors into the ... Serine, tyrosine and threonine kinases are the three most common. Especially, the receptor tyrosine kinases (RTK) play an ... 3.) The process of dimerization activates the tyrosine kinase region of each individual monomer. Both of these tyrosine kinases ...
... receptor tyrosine kinases, Ras or Raf proteins. Although no MKK1/2 or ERK1/2 inhibitors were developed for clinical use, kinase ... MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... Dephospho-(reductase kinase) kinase (EC 220.127.116.11). *AMP-activated protein kinase α *PRKAA1 ...
... regulation of mitogen-activated protein kinases. Protein phosphatases-a phylogenetic perspective ... Nonreceptor tyrosine phosphatases in cellular signaling: regulation of mitogen-activated protein kinases. Article Abstract:. ... Research has been conducted on the nonreceptor tyrosine phosphatases. The regulation of the mitogen-activated protein kinase ... The structure, catalysis and regulation of the protein phosphatases and protein tyrosine phosphatases have been investigated. ...
Mitogen-activated protein kinase. TKI. Tyrosine kinase inhibitor. PCA. Principal component analysis ... HER kinase axis receptor dimer partner switching occurs in response to EGFR tyrosine kinase inhibition despite failure to block ... Reduced proteolytic shedding of receptor tyrosine kinases is a post-translational mechanism of kinase inhibitor resistance. ... Endocytosis of receptor tyrosine kinases. Cold Spring Harb. Perspect. Biol. 5:a017459-a017459, 2013.CrossRefGoogle Scholar ...
"Protein tyrosine phosphatase epsilon inhibits signaling by mitogen-activated protein kinases". Mol. Cancer Res. 1 (7): 541-50. ... "Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase ... Receptor-type tyrosine-protein phosphatase epsilon is an enzyme that in humans is encoded by the PTPRE gene. The protein ... "Entrez Gene: PTPRE protein tyrosine phosphatase, receptor type, E". Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A ...
Previous MEK (methyl ethyl ketone) inhibitor or prior treatment with EGFR TKI (tyrosine kinase inhibitor). ... mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. The MAP kinase pathway could be ... Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild ... Mitogen-activated Protein Kinase 1 (MEK 1), Proto-oncogene B-Raf (BRAF), and LKB1 [ Time Frame: At enrollment ]. Number of ...
NO, nitric oxide; eNOS, endothelial nitric oxide synthase; MEK, mitogen-activated protein kinase kinase; Janus tyrosine kinase ... soluble fms-like tyrosine kinase-1; sTrkB, soluble neurotrophic tyrosine kines, receptor, type 2; c-PTIO, carboxy-2-phenyl-4, 4 ... JAK), STAT, signal transducer and activator of transcription; AMPK, AMP-activated protein kinase. (Drawn from data and concepts ...
Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen- activated protein kinases p44, p42, and p41 in vascular ... Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen- activated protein kinases p44, p42, and p41 in vascular ... Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen- activated protein kinases p44, p42, and p41 in vascular ... Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen- activated protein kinases p44, p42, and p41 in vascular ...
Mitogen-Activated Protein Kinase, and Phosphatidylinositol 3-Kinase Pathways in Lung Cancers *Federico De Marchi ... Coexistence of KRAS mutation with mutant but not wild-type EGFR predicts response to tyrosine-kinase inhibitors in human lung ... The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell ... patients treated with tyrosine kinase inhibitors. Anticancer Res 30 (5): 1667-1671. ...
Relapse rates are high even with the integration of first-generation FMS-like tyrosine kinase 3 (FLT3) inhibitors in pre- and ... In the present study, we investigated the nature of pro-survival signalling in primary residual tyrosine kinase inhibitor (TKI ... and a synergistic combination with a mitogen-activated protein kinase (MEK) inhibitor identified for potential therapeutic ... Combination of a mitogen-activated protein kinase inhibitor with the tyrosine kinase inhibitor pacritinib combats cell adhesion ...
"Interaction of mitogen-activated protein kinases with the kinase interaction motif of the tyrosine phosphatase PTP-SL provides ... Ogata M, Oh-hora M, Kosugi A, Hamaoka T (1999). "Inactivation of mitogen-activated protein kinases by a mammalian tyrosine- ... "A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine ... "PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ...
Lipopolysaccharide stimulates the tyrosine phosphorylation of mitogen-activated protein kinases p44, p42, and p41 in vascular ... ERK kinases, p42/44 kinases; MEK, mitogen-activated protein kinase kinase; PKC protein kinase C; PC-PLC, phosphatidylcholine- ... These kinases are known to be directly activated by mitogen-activated protein kinase kinase, a kinase directly upstream of the ... LPS-activated PKC ζ phosphorylated MAP kinase kinase, the kinase directly upstream of the ERK kinases. LPS-induced cytokine ...
... fms-like tyrosine kinase receptor-3; GSK, glycogen synthase kinase; JAK, Janus kinase; JNK, Jun N-terminal kinase; MEF, myocyte ... mitogen-activated protein kinase/ERK kinase; MERM, ezrin/radixin/moezin family of cytoskeletal linkers; mTOR, mammalian target ... phosphoinositide-dependent kinase; PI3K, phosphoinositide-3 kinase; PKB, protein kinase B; PKC, protein kinase C; PLC, ... Rho-associated kinase; ROS, reactive oxygen species; RTK, receptor tyrosine kinase; SERT, 5-HT transporter; SOC, store-operated ...
tyrosine kinase inhibitors. RTKs. receptor tyrosine kinases. MAPK. Mitogen-activated protein kinase. mTOR. mammalian target of ... Zoom in on tyrosine kinases. Indicated in the map is EGFR (unchanged) as well as a few upregulated receptor tyrosine kinases ... 2007) Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 445, 437-441. ... of alternative tyrosine kinases that can reactivate the downstream signaling after inhibition of a primary tyrosine kinase drug ...
The neurogenic effect of Aβ is mediated through tyrosinekinase phosphorylation and the MAPK (mitogen-activated protein kinase) ... These included Genistein, an inhibitor of tyrosine kinases (TyrK) and a competitive inhibitor of ATP in other protein kinase ... The inhibition of neurogenesis by Genistein suggests that tyrosine kinases are involved in this process. These kinases include ... 4A). Similarly, treatment with U0126, a selective inhibitor of MEK (MAP kinase kinase), did not induce any change in total ...
InhibitionEpidermal GrowthPhosphorylationSerine-threoniPathwayPhosphatidylinositol 3-KinaERK2ActivatesPlatelet-deriveCascadesSpecificitySelectivePhosphorylateCellularTransmembraneDownstreamGeneCytoplasmicFamily of tyrosine kinasesActivationJNKsRTKsNonreceptor tyrosine kinasesProliferationEndothelial CellsCatalyticPI3KInteractionUpstreamSAPK
- We investigated upstream components of the response to hypertonicity in lung epithelial cells and found that before extracellular signal-regulated kinase activation and aquaporin synthesis, the membrane-bound prohormone neuregulin 1-β is cleaved and binds to human epidermal growth factor receptor 3 (HER3). (wustl.edu)
- in particular, investigating the level of MKK7 phosphorylation in response to external stresses induced by the tyrosine kinase receptor inhibitor Sunitinib. (bmj.com)
- The activation of arginase was preceded by a transient increase in intracellular cAMP, tyrosine kinase phosphorylation, and p38 mitogen-activated protein kinase (MAPK) activation. (jimmunol.org)
- Estrogen also stimulates tyrosine phosphorylation of NMDA receptors via an src tyrosine kinase/MAPK pathway. (lmu.edu)
- Immunoprecipitation with an antiphosphotyrosine antibody (PY20), followed by Western analysis using pan-ERK, revealed a marked concentration-dependent increase in tyrosine phosphorylation of ERK2 in response to EGF treatment. (elsevier.com)
- The mobility shift and tyrosine phosphorylation of ERK2 was observed as early as 1 min after treatment with 10 ng/ml EGF. (elsevier.com)
- Although ERK1 displayed a moderate mobility shift in response to EGF, tyrosine phosphorylation of this MAP kinase was not appreciably increased by EGF. (elsevier.com)
- Electrophoretic migration, tyrosine phosphorylation, and MBP kinase activity of the ERK54 and ERK87 was not effected regardless of EGF concentration or duration of treatment. (elsevier.com)
- EGF, in a concentration- and time-dependent manner, increases tyrosine phosphorylation and MBP kinase activity (i.e. activation) of ERK2, and to a lesser degree ERK1, suggesting that the activation of MAP kinase may mediate the mitogenic action of EGF in pGCs. (elsevier.com)
- Davis, John S. / Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer cultures of porcine granulosa cells . (elsevier.com)
- Kinase cascade (sometimes called phosphorylation cascade) can activate MAP kinase. (wikibooks.org)
- We used bovine and human brain microvessel EC (BBMEC, and HBMEC) to study LPS-induced protein tyrosine phosphorylation. (elsevier.com)
- LPS rapidly induced the tyrosine phosphorylation of several proteins in BBMEC and HBMEC, which was detectable by 5 to 15 min, reached a maximum by 30 min, and declined by 60 to 90 min. (elsevier.com)
- The increase in tyrosine phosphorylation was apparent following stimulation with LPS at 0.1 ng/ml and was dose dependent up to 100 ng/ml. (elsevier.com)
- Similar changes in tyrosine phosphorylation were induced by smooth and rough LPS as well as lipid A, but not by the inactive lipid A analogue, Rhodopseudomonas sphaeroides diphosphoryl lipid A. Pretreatment of EC with the tyrosine kinase inhibitor, herbimycin A, inhibited LPS-stimulated protein tyrosine phosphorylation and LPS-mediated lactic dehydrogenase release from BBMEC and IL-6 release from HBMEC in a dose-dependent manner. (elsevier.com)
- LPS-induced protein tyrosine phosphorylation in HBMEC and BBMEC was soluble CD14 dependent, since pretreatment of these cells with anti-hCD14 mAb inhibited the LPS-induced tyrosine phosphorylation of p44, p42, and p41. (elsevier.com)
- These findings demonstrate for the first time that increased protein tyrosine phosphorylation and activation of mitogen-activated protein kinases occur rapidly after LPS stimulation of EC in the presence of soluble CD14. (elsevier.com)
- In vivo and in vitro , phosphorylation of tyrosine oftentimes precedes phosphorylation of threonine, although phosphorylation of either residue can occur in the absence of the other. (wikipedia.org)
- This tandem activation loop phosphorylation (that was proposed to be either distributive or processive, dependent on cellular environment) is performed by members of the Ste7 protein kinase family, also known as MAP2 kinases . (wikipedia.org)
- MAP2 kinases in turn, are also activated by phosphorylation, by a number of different upstream serine-threonine kinases ( MAP3 kinases ). (wikipedia.org)
- PD 166866 also inhibited bFGF-induced tyrosine phosphorylation of the 44- and 42-kDa (ERK 1/2) mitogen-activated protein kinase isoforms in L6 cells, presumably via inhibition of bFGF-stimulated FGFR-1 tyrosine kinase activation. (aspetjournals.org)
- The interaction of GH with GH receptors (GHR) on target cells promotes the association of the cellular tyrosine kinase JAK2 with the GHR, initiating tyrosine phosphorylation of GHR and JAK2, and activation of multiple signaling cascades. (biomedsearch.com)
- Cells were counted after 24 h and after inhibition of each signal, tyrosine phosphorylation or actin depolymerization. (biomedsearch.com)
- Glycogen synthase kinase-3beta induces neuronal cell death via direct phosphorylation of mixed lineage kinase 3. (semanticscholar.org)
- Recent research has also implicated Grb2 in tyrosine phosphorylation of PLD2 that also involves Sos and the ERK pathway. (hindawi.com)
- Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. (pnas.org)
- To understand the full spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC) in differentiated brown adipocytes. (pnas.org)
- Insulin or IGF-1 binding initiates a complex cascade of events, starting with phosphorylation of specific tyrosine residues on the insulin and the IGF-1 receptors ( 2 ). (pnas.org)
- We have studied tyrosine phosphorylated effectors and interactors in the EGF pathway ( 5 , 6 ) and others have used MS to study tyrosine phosphorylation of the insulin pathway in white adipocytes ( 7 ). (pnas.org)
- Labeling three cell states by SILAC allows measuring a time course of activation of tyrosine phosphorylation by quantifying the relative protein amounts after anti-phosphotyrosine immunoprecipitation. (pnas.org)
- Here, we quantitatively assess temporal dynamics of tyrosine phosphorylation events upon insulin stimulation in differentiated brown adipocytes. (pnas.org)
- The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. (abcam.com)
- To understand the dynamic operation of signaling cascades, we have developed a method enabling the simultaneous quantification of tyrosine phosphorylation of specific residues on dozens of key proteins in a time-resolved manner, downstream of epidermal growth factor receptor (EGFR) activation. (mcponline.org)
- Database searching and manual confirmation of peptide phosphorylation site assignments led to the identification of 78 tyrosine phosphorylation sites on 58 proteins from a single analysis. (mcponline.org)
- Replicate analyses of a separate biological sample provided both validation of this first data set and identification of 26 additional tyrosine phosphorylation sites and 18 additional proteins. (mcponline.org)
- The data set of quantitative temporal phosphorylation profiles was further characterized by self-organizing maps, which resulted in identification of several cohorts of tyrosine residues exhibiting self-similar temporal phosphorylation profiles, operationally defining dynamic modules in the EGFR signaling network consistent with particular cellular processes. (mcponline.org)
- The presence of novel proteins and associated tyrosine phosphorylation sites within these modules indicates additional components of this network and potentially localizes the topological action of these proteins. (mcponline.org)
- These pathways involve a number of components whose interactions are required to carry out regulatory processes and that are themselves regulated by covalent modifications, including phosphorylation on tyrosine as well as serine and threonine residues. (mcponline.org)
- p53 phosphorylation is mediated by several cellular kinases, including Chks (Checkpoint Kinases), CSNK1-Delta (Casein Kinase-1-Delta), CSNK2 (Casein Kinase-2), PKA (Protein Kinase A), CDK7 (Cyclin-Dependent Kinase-7), DNA-PK (DNA-Activated Protein Kinase), HIPK2 (Homeodomain-Interacting Protein Kinase-2), and JNK (Jun NH2-terminal kinase). (thermofisher.com)
- The main kinases involved in p53 phosphorylation include Chk1 (Cell Cycle Checkpoint Kinase-1) and Chk2 (Cell Cycle Checkpoint Kinase-2). (thermofisher.com)
- The list of IRS kinases implicated in the development of insulin resistance is growing rapidly, concomitant with the list of potential Ser/Thr phosphorylation sites in IRS proteins. (physiology.org)
- The first kinase identified as being responsible for the phosphorylation of serine 133 is a cAMP-dependent protein kinase (protein kinase A [PKA]), which is activated by an increase in the intracellular cAMP level. (ahajournals.org)
- KID represents kinase inducible domain and contains serine 133, the phosphorylation of which is required for the activation of CREB. (ahajournals.org)
- this was seen as a reduction in Fyn autophosphorylation, reduced phosphorylation of in vivo substrates, and inhibition of transcription from a Src-family kinase response element linked to a luciferase reporter. (asm.org)
- Autophosphorylation of tyrosine kinases and subsequent phosphorylation of key intracellular signaling proteins are the earliest detectable events following activation of a variety of receptors and are required for transcriptional events that ultimately mediate cellular responses ( 71 , 72 ). (asm.org)
- Phosphorylation of the Cbl protein follows the engagement of a variety of cell surface receptors that either possess a cytoplasmic tyrosine kinase domain or are noncovalently linked to cytoplasmic or membrane-anchored tyrosine kinases. (asm.org)
- In skeletal muscle, the FH + and FH − groups had equivalent insulin stimulation of insulin receptor tyrosine phosphorylation. (diabetesjournals.org)
- The molecular mechanism underlying defective insulin-stimulated glucose transport activity can be attributed to increases in intramyocellular lipid metabolites such as fatty acyl CoAs and diacylglycerol, which in turn activate a serine/threonine kinase cascade, thus leading to defects in insulin signaling through Ser/Thr phosphorylation of insulin receptor substrate (IRS)-1. (diabetesjournals.org)
- A similar mechanism is also observed in hepatic insulin resistance associated with nonalcoholic fatty liver, which is a common feature of type 2 diabetes, where increases in hepatocellular diacylglycerol content activate protein kinase C-ε, leading to reduced insulin-stimulated tyrosine phosphorylation of IRS-2. (diabetesjournals.org)
- While the unsaturated FFAs oleate and linoleate inhibited both basal and insulin-stimulated glycogen synthesis, the saturated FFA palmitate reduced only insulin-stimulated glycogen synthesis, and was found to inhibit insulin-stimulated phosphorylation of glycogen synthase kinase-3 and protein kinase B (PKB). (garvan.org.au)
- However, no effect of palmitate was observed on tyrosine phosphorylation, p85 association, or phosphatidylinositol 3-kinase activity in IRS-1 immunoprecipitates. (garvan.org.au)
- In contrast, palmitate promoted phosphorylation of mitogen-activated protein MAP) kinases. (garvan.org.au)
- Expression of PAG in COS cells results in recruitment of endogenous Csk, altered Src kinase activity, and impaired phosphorylation of Src-specific substrates. (rupress.org)
- Lyn's role in activation is mediated by the phosphorylation of tyrosine residues within immunoreceptor tyrosine-based activation motifs of proteins such as Igα, Igβ, and CD19, and the subsequent recruitment of enzymes such as Syk, phospholipase Cγ2 (PLCγ2), and phosphatidyl inositol-3 kinase ( 14 ). (rupress.org)
- As a balance, there is suppression of B cell stimulation from Lyn-dependent phosphorylation of tyrosine residues within immunoreceptor tyrosine-based inhibitory motifs in proteins such as CD22, PIR-B, and FcγRIIb1, with the concomitant recruitment to the plasma membrane of phosphatases such as SHP-1 and SHIP-1 ( 15 - 21 ). (rupress.org)
- Lyn-deficient B cells fail to recruit protein tyrosine phosphatases to the plasma membrane due to defects in phosphorylation of inhibitory receptors ( 16 - 19 , 22 ). (rupress.org)
- Additional sites of tyrosine and serine phosphorylation are indicated. (biologists.org)
- A MAP3K that is activated by extracellular stimuli phosphorylates a MAP2K on its serine and threonine residues, and then this MAP2K activates a MAP kinase through phosphorylation on its serine and tyrosine residues. (thefullwiki.org)
- Mitogen activated kinase kinase 7 (MKK7) is a selective upstream regulator of the c-Jun N-terminal kinase (JNK) pathway. (bmj.com)
- Finally, estrogen-mediated enhancement of long-term potentiation in hippocampal slices is mediated by activation of an src tyrosine kinase pathway. (lmu.edu)
- The RhoA/protein kinase B (Akt)/mitogen-activated protein (MAP) kinases, including p38 MAP kinase, extracellular signal-regulated protein kinase, and Jun NH 2 -terminal kinase axis in RAW 264.7 cells, was identified as Gas6/Mer downstream signaling pathway for the upregulation of HGF mRNA and protein. (aspetjournals.org)
- Our data provide evidence that macrophages can be reprogrammed by Gas6 to promote epithelial proliferation and wound repair via HGF, which is induced by the Mer/RhoA/Akt/MAP kinase pathway. (aspetjournals.org)
- The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). (clinicaltrials.gov)
- It also can bind to G-protein coupled estrogen receptor (GPER) [ 11 ] and mediates nongenomic action that is rapid in onset and short in duration such as changes in vasomotor tones through kinase activation and intracellular signaling pathway [ 12 ]. (hindawi.com)
- The JNK (c-Jun N-terminal kinase) pathway is activated by diverse stresses and can have an effect on a number of different cellular processes. (biochemsoctrans.org)
- Not surprisingly, activating mutations in upstream tyrosine kinase receptor (FGFR3) seem to be mutually exclusive with RAS mutations, given that both signal through a common downstream pathway in urothelial oncogenesis. (thefreelibrary.com)
- A variety of agents and conditions that induce insulin resistance, such as TNFα and free fatty acids, activate a number of protein kinases that target elements along the insulin-signaling pathway. (physiology.org)
- This results in defective inhibitory signaling and as a consequence, Lyn-deficient B cells are hyperresponsive to BCR stimulation and show enhanced proliferation, calcium flux, and activation of the mitogen-activated protein kinase pathway ( 15 - 19 , 23 ). (rupress.org)
- In the second report, we show that RET/PTC3 activates Erk8, a new member of "atypical" MAP kinases group, by an Abl-dependent but Src-independent mechanism and demonstrate a key role for Tyr981 of RET/PTC3 in the initiation of such signaling pathway. (unina.it)
- The ERK1/2 (also known as classical MAP kinases) signaling pathway is preferentially activated in response to growth factors and phorbol ester (a tumor promoter), and regulates cell proliferation and cell differentiation. (thefullwiki.org)
- MAP kinases were detected having mol wts of 87K (ERK87), 54K (ERK54), 44K (ERK1), and 42K (ERK2). (elsevier.com)
- In-gel myelin basic protein (MBP) kinase assays revealed significant MBP kinase activity associated with ERK1 and ERK2 in total cell lysates and ERK2 in PY20 immunoprecipitates. (elsevier.com)
- 1. Extracelluar-signal regulated kinases (ERK1, ERK2)-ERK1/2 produce long lasting changes in cell signaling. (wikibooks.org)
- X-ray structure of the ERK2 MAP kinase in its active form. (wikipedia.org)
- Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. (wikipedia.org)
- As an aggregate, these studies support the hypothesis that one way by which LPS activates the ERK kinases is via activation of PC-PLC and that activation of a PC-PLC is an important component of macrophage activation by LPS. (jimmunol.org)
- No studies have determined how LPS activates the ERK kinases, but several studies provided clues that have led to our hypothesis. (jimmunol.org)
- This causes a conformational change in the receptor that activates the kinase domain and results in autophosphorylation and initiation of divergent signal transduction cascades ( 2 ). (aacrjournals.org)
- In the particular case of EGFR, ligand binding activates the receptor and dimerization results in autophosphorylation of selected tyrosine sites in the C-terminal region ( 1 ). (mcponline.org)
- 6 In particular, EGFR activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) 7 and AKT 8 signaling from EEA1-positive (early endosome antigen 1) early endosomes. (ahajournals.org)
- In contrast, PD 166866 had no effect on c-Src, platelet-derived growth factor receptor-β, epidermal growth factor receptor or insulin receptor tyrosine kinases or on mitogen-activated protein kinase, protein kinase C and CDK 4 at concentrations as high as 50 μM. (aspetjournals.org)
- 1990 ) Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. (biologists.org)
- PDGFRb is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. (thermofisher.com)
- This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. (bio-rad.com)
- The MAP kinase transduction system is particularly important in growth factors signaling, which in turn control cell growth, proliferation, differentiation, survival and migration by activating receptor tyrosine kinase (RTK) family members, as platelet-derived growth factor (PDGF) and RET. (unina.it)
- Background -Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. (ahajournals.org)
- Introduction Mitogen Activated Protein (MAP) kinase signalling cascades play significant roles in the development of cardiac hypertrophy in response to external stresses. (bmj.com)
- The amplification of the original signal was decreased since the kinase cascades are not allowed to move freely to bind new substrate. (wikibooks.org)
- A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. (umassmed.edu)
- The protein product of the c- cbl proto-oncogene has emerged as a prominent component of tyrosine kinase-mediated signal transduction cascades (reviewed in references 33 and 42 ). (asm.org)
- β-arrestins also bind and scaffold members of such signaling cascades as the mitogen-activated protein kinases (MAPKs). (sciencemag.org)
- Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. (nih.gov)
- MKK3 and MKK6 are two closely related dual-specificity protein kinases that activate p38 MAP kinase (1-5). (creativebiomart.net)
- MKK6 is a dual specificity mitogen-activated protein kinase that was first cloned by PCR using degenerate primers for the conserved kinase domain of MKKs (Han et al. (springer.com)
- 2001). „Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions" . (wikipedia.org)
- ie MAP2K can be a dual-specificity kinase ). (thefullwiki.org)
- One class of mitogens selective for vascular endothelial cells include vascular endothelial growth factor (referred to as VEGF or VEGF-A) and the homologues placenta growth factor (PlGF), VEGF-B and VEGF-C. (google.es)
- Molecular determinants that mediate selective activation of p38 MAP kinase isoforms. (springer.com)
- Studies performing knockout of these genes have revealed that these kinase are associated with apoptosis (the cellular signaling leading to the deal of potentially cancerous cells) and immune response. (wikibooks.org)
- MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens , osmotic stress , heat shock and proinflammatory cytokines . (wikipedia.org)
- The similar gene predominately expressed in mouse brain was found to associate with, and thus regulate the activity and cellular localization of MAP kinases. (wikipedia.org)
- In contrast, the compound had no effect on MAP kinase activation or cellular proliferation in response to granulocyte-macrophage colony-stimulating factor. (bloodjournal.org)
- Mitogen-activated protein (MAP) kinases ( EC 18.104.22.168 ) are serine/threonine-specific protein kinases that respond to extracellular stimuli ( mitogens ) and regulate various cellular activities, such as gene expression , mitosis , differentiation , proliferation, and cell survival/ apoptosis . (thefullwiki.org)
- Receptor tyrosine kinases is a transmembrane structure that anchors into the membrane. (wikibooks.org)
- All ErbB family members share common features including an extracellular ligand-binding domain, a transmembrane portion, and an intracellular protein tyrosine kinase domain. (aacrjournals.org)
- To date, their cofunction in neural migration has not been reported, although HB-GAM is known to mediate haptotactic migration of perinatal rodent forebrain cells via the receptor-type tyrosine phosphatase β/ζ, which is another transmembrane receptor of HB-GAM ( Maeda and Noda, 1998 ). (rupress.org)
- For instance, target and alternative receptor tyrosine kinases (RTKs) can exhibit enhanced activities via increased expression even in the absence of gene amplification, 4 , 10 , 35 , 46 , 49 including by means of modulated ligand binding and/or receptor oligomerization. (springer.com)
- Receptor-type tyrosine-protein phosphatase epsilon is an enzyme that in humans is encoded by the PTPRE gene. (wikipedia.org)
- The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. (wikipedia.org)
- Protein tyrosine phosphatase receptor-type R is an enzyme that in humans is encoded by the PTPRR gene. (wikipedia.org)
- The FGF receptor family consists of a group of four homologous receptor tyrosine kinases transcribed either as distinct gene products or by alternative splicing of their primary transcripts. (aspetjournals.org)
- An isolated nucleic acid molecule encoding a novel human receptor type tyrosine kinase gene, KDR, is disclosed. (google.es)
- This gene encodes a member of a family of nuclear-localized protein kinases. (nih.gov)
- This work provides the results of a screen for genes transcriptionally regulated by Met in several cell lines and addresses the functions of the highly inducible gene Mig6 (Mitogen-inducible-gene6, also called Gene 33 and RALT). (uni-muenchen.de)
- The Abl gene expresses a membrane-associated protein, a tyrosine kinase , and the BCR-Abl transcript is also translated into a tyrosine kinase containing domains from both the BCR and ABL1 genes. (wikipedia.org)
- The activity of tyrosine kinases is typically regulated in an auto-inhibitory fashion, but the BCR-Abl fusion gene codes for a protein that is "always on" or constitutively activated, leading to impaired DNA binding and unregulated cell division (i.e. cancer). (wikipedia.org)
- 1992 ) tek , a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. (biologists.org)
- Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the MAPK9 gene . (wikidoc.org)
- The protein encoded by this gene is a member of the MAP kinase family. (wikidoc.org)
- This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. (wikidoc.org)
- This gene and MAPK8 are also known as c-Jun N-terminal kinases. (wikidoc.org)
- Protein kinases and transcription factors transmit the signals from the external stimuli to the genome, resulting in the modification of gene expression profile of the cells to accommodate to the environmental changes. (ahajournals.org)
- Our data suggest that BFT-stimulated IL-8 secretion involves tyrosine kinase-dependent activation of nuclear factor-κB (NF-κB) as well as activation of the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-related kinase. (asm.org)
- We have examined porcine granulosa cells (pGCs) for the presence of immunodetectable mitogen-activated protein (MAP) kinases (extracellular signal-regulated kinases, ERK) and have further studied the effects of epidermal growth factor (EGF) on the activation of these kinases. (elsevier.com)
- Our data also suggest that a herbimycin-sensitive step, presumably a tyrosine kinase, is involved in mediating LPS-induced human EC activation and IL-6 secretion. (elsevier.com)
- In contrast to the classical MAP kinases, these atypical MAPKs require only a single residue in their activation loops to be phosphorylated. (wikipedia.org)
- This study uses human alveolar macrophages to determine whether activation of a phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) is linked to activation of the p42/44 (ERK) kinases by LPS. (jimmunol.org)
- 22 , 23 used a dominant-negative mutant of PKC ζ to block serum and TNF activation of the ERK kinases. (jimmunol.org)
- In fibroblasts, ET-1 suppressed apoptosis via the ETA receptor through activation of p42/p44 MAP kinase whereas the mechanism behind ETB receptor-mediated endothelial apoptosis remains unclarified. (nii.ac.jp)
- However, the mitogenic effect of pressure requires only tyrosine kinase and PKCalpha activation. (biomedsearch.com)
- Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase. (semanticscholar.org)
- STI 571 inhibited c-kit autophosphorylation, activation of mitogen-activated protein (MAP) kinase, and activation of Akt without altering total protein levels of c-kit, MAP kinase, or Akt. (bloodjournal.org)
- STI 571 had a more potent inhibitory effect on the kinase activity of this mutant receptor than it did on ligand-dependent activation of the wild-type receptor. (bloodjournal.org)
- Using biochemical and cell-based assays of receptor activation, signal transduction, proliferation, and apoptosis, we found that STI 571 inhibited the SLF-dependent activation of wild-type c-kit kinase activity. (bloodjournal.org)
- We suggest that the migration defect depends on impaired HB-GAM-induced Src kinase activation and haptotactic migration. (rupress.org)
- As the N-terminal Y177 and CC domains from BCR encode the constitutive activation of the ABL1 kinase, these regions are targeted in therapies to downregulate BCR-ABL kinase activity. (wikipedia.org)
- The interaction of activation kinases with MKK6 is. (springer.com)
- Mechanism of p38 MAP kinase activation in vivo. (springer.com)
- Expression and activation of mitogen-activated protein kinase kinases-3 and -6 in rheumatoid arthritis. (springer.com)
- The MAP kinase cascade leads to enhanced cell growth, while the Cbl/CAP cascade mediates glucose transport through activation of the GTP-binding protein TC10 and the recruitment of the CIP4/Gappex-5 complex to the plasma membrane ( 73 ). (physiology.org)
- Another domain, the kinase inducible domain, containing serine 133, is necessary and sufficient for transcriptional activation of target genes. (ahajournals.org)
- Fyn is a prototype Src-family tyrosine kinase that plays specific roles in neural development, keratinocyte differentiation, and lymphocyte activation, as well as roles redundant with other Src-family kinases. (asm.org)
- The activity of the isolated kinase domain and auto-activation of the full-length enzyme were inhibited with similar potency. (biochemj.org)
- Also, by using an alternative Erk8 splice variant, Erk8, lacking the C-terminal domain, we establish a role for this region in the activation of this MAP kinase by RET/PTC3. (unina.it)
- 3 PDGF ligands, established as potent mitogens, chemotactic agents, and inducers of matrix synthesis, produce effects by dimerization and activation of PDGF-receptor (PDGFr) subunits. (ahajournals.org)
- 2. c-Jun N terminal kinases (JNKs) also known as Stress Activated Protein Kinase (SAPK). (wikibooks.org)
- In mammals, there are many MAP kinases with different biological functions, grouped in distinctly regulated groups, ERK1/2 (extracellular signal related kinase, ERK), JNKs (jun amino terminal kinase, JNK), p38 and "atypical" MAP kinases. (unina.it)
- c-Jun N-terminal kinases (JNKs), ( MAPK8 , MAPK9 , MAPK10 ) also known as stress-activated protein kinases (SAPKs). (thefullwiki.org)
- The ErbB1 and ErbB2 receptor tyrosine kinases (RTKs) play important roles in the development of numerous types of human cancer and, as such, have been pursued as anticancer targets. (aacrjournals.org)
- We have used RT-PCR to screen pluripotent murine embryonic stem cells to identify receptor tyrosine kinases (RTKs) potentially involved in the determination or differentiation of cell lineages during early mouse development. (biologists.org)
- Among these, receptor tyrosine kinases (RTKs), such as vascular endothelial growth factor receptor-2 (VEGFR2) and fibroblast growth factor receptor-1 (FGFR1), are essential regulators of such essential EC activities as proliferation, migration, angiogenesis, and vascular permeability. (ahajournals.org)
- β-arrestins bind and direct the activity of several nonreceptor tyrosine kinases in response to 7TMR stimulation. (sciencemag.org)
- One potential target for systemic therapy is Src family nonreceptor tyrosine kinases, which are overexpressed in these tumors and induce pleiotropic effects, including increased proliferation, enhanced survival, stimulation of angiogenesis, and changes in motility. (aacrjournals.org)
- One promising target in this effort is found in the Src family of nonreceptor tyrosine kinases. (aacrjournals.org)
- Thus the role of mammalian ERK1/2 kinases as regulators of cell proliferation is not a generic, but a highly specialized function. (wikipedia.org)
- Extracellular pressure stimulates colon cancer cell proliferation via a mechanism requiring PKC and tyrosine kinase signals. (biomedsearch.com)
- However, global tyrosine kinase blockade (genistein) and PKC blockade (calphostin C) negated pressure-induced proliferation. (biomedsearch.com)
- ITK (interleukin-2-inducible T-cell kinase) is a critical component of signal transduction in T-cells and has a well-validated role in their proliferation, cytokine release and chemotaxis. (biochemj.org)
- The present invention relates to an isolated nucleic acid molecule (polynucleotide) which encodes a human receptor tyrosine kinase, KDR, which is expressed on human endothelial cells. (google.es)
- Vascular endothelial growth factor (VEGF) is a major mitogen for endothelial cells and enhances vascular permeability. (aacrjournals.org)
- however, the interaction with JNK occurs through a mitogen-activated protein KIM (kinase interaction motif) in a region distinct from the Bruton's tyrosine kinase-binding domain. (biochemsoctrans.org)
- The present invention also provides for diagnostic and therapeutic methods based on the interaction between BDNF and/or NT-3 and trkB,and for a number of orphan receptor molecules, including members of the TIE and EHK family of receptor tyrosine kinases. (patentgenius.com)