Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.src-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.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.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.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.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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.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.Proto-Oncogene Proteins c-fyn: Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.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.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.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.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.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.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Protein 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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.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.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.PhosphoproteinsTyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.Receptor-Like Protein Tyrosine Phosphatases, Class 2: A subclass of receptor-like protein tryosine phosphatases that contain multiple extracellular immunoglobulin G-like domains and fibronectin type III-like domains. An additional memprin-A5-mu domain is found on some members of this subclass.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 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.Protein Tyrosine Phosphatase, Non-Receptor Type 2: A subtype of non-receptor protein tyrosine phosphatase that is closely-related to PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1. Alternative splicing of the mRNA for this phosphatase results in the production at two gene products, one of which includes a C-terminal nuclear localization domain that may be involved in the transport of the protein to the CELL NUCLEUS. Although initially referred to as T-cell protein tyrosine phosphatase the expression of this subtype occurs widely.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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)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.Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Receptor-Like Protein Tyrosine Phosphatases, Class 3: A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.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.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.Lactams, Macrocyclic: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.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.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.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.Benzoquinones: Benzene 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-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.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.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 enzymesFocal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.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.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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Mitogen-Activated Protein Kinase 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.Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.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.Receptor-Like Protein Tyrosine Phosphatases, Class 4: A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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).Kinetics: The rate dynamics in chemical or physical systems.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.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).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.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.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.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.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.Protein Tyrosine Phosphatases, Non-Receptor: A subcategory of protein tyrosine phosphatases that occur in the CYTOPLASM. Many of the proteins in this category play a role in intracellular signal transduction.Receptor-Like Protein Tyrosine Phosphatases, Class 5: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.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.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 1.14.16.2.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Protein Tyrosine Phosphatase, Non-Receptor Type 12: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of a N-terminal catalytic domain and a large C-terminal domain that is enriched in PROLINE, GLUTAMIC ACID, SERINE, and THREONINE residues (PEST sequences). The phosphatase subtype is ubiquitously expressed and implicated in the regulation of a variety of biological processes such as CELL MOVEMENT; CYTOKINESIS; focal adhesion disassembly; and LYMPHOCYTE ACTIVATION.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.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.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.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.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Benzamides: BENZOIC ACID amides.Cell Line, Tumor: A cell line derived from cultured tumor cells.Janus Kinase 1: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.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.PiperazinesSequence 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.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.SH2 Domain-Containing Protein Tyrosine Phosphatases: A subcategory of protein tyrosine phosphatases that contain SH2 type SRC HOMOLOGY DOMAINS. Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via their SH2 domain.Proto-Oncogene Proteins c-vav: Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).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.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.Proto-Oncogene Proteins c-hck: Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.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.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).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.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.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Oncogene Protein pp60(v-src): A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine.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.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.Receptors, IgE: Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.QuinazolinesStaurosporine: 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)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.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.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 Tyrosine Phosphatase, Non-Receptor Type 13: A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing five different PDZ domains, and a carboxyl-terminal phosphatase domain. In addition to playing a role as a regulator of the FAS RECEPTOR activity this subtype interacts via its PDZ and FERM domains with a variety of INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS.Proto-Oncogene Proteins c-cbl: Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.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.Mice, Inbred C57BLDose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.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.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.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.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Antigens, CD45: High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.Receptor-Like Protein Tyrosine Phosphatases: A subcategory of protein tyrosine phosphatases that are bound to the cell membrane. They contain cytoplasmic tyrosine phosphatase domains and extracellular protein domains that may play a role in cell-cell interactions by interacting with EXTRACELLULAR MATRIX components. They are considered receptor-like proteins in that they appear to lack specific ligands.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.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.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.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.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.Proto-Oncogene Proteins c-fes: Proto-oncogene proteins fes are protein-tyrosine kinases with a central SH2 DOMAIN. It has been implicated in SIGNAL TRANSDUCTION PATHWAYS for CELL DIFFERENTIATION of a variety of cell types including MYELOID PROGENITOR CELLS. Fes proto-oncogene proteins also bind TUBULIN and promote MICROTUBULE assembly.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.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Receptor-Like Protein Tyrosine Phosphatases, Class 7: A subclass of receptor-like protein tryosine phosphatases that contain a short extracellular domain, a cytosolic kinase-interaction domain, and single protein tyrosine kinase domain.Antigens, CD79: A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Paxillin: Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.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.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.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).Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.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.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.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Myristates: Salts and esters of the 14-carbon saturated monocarboxylic acid--myristic acid.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Leukemia, Basophilic, Acute: A rare acute myeloid leukemia in which the primary differentiation is to BASOPHILS. It is characterized by an extreme increase of immature basophilic granulated cells in the bone marrow and blood. Mature basophils are usually sparse.Phosphoserine: The phosphoric acid ester of serine.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)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.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.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.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.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.Benzylidene Compounds: Compounds containing the PhCH= radical.Molecular Weight: The sum of the weight of all the atoms in a molecule.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.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.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.Receptor-CD3 Complex, Antigen, T-Cell: Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.Sperm Capacitation: The structural and functional changes by which SPERMATOZOA become capable of oocyte FERTILIZATION. It normally requires exposing the sperm to the female genital tract for a period of time to bring about increased SPERM MOTILITY and the ACROSOME REACTION before fertilization in the FALLOPIAN TUBES can take place.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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.
Syk Antibody, anti-human, REAfinity™ - Recombinant antibodies - MACS Antibodies - Products - Miltenyi Biotec - Österreich
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SpleenImmunoreceptor tyrosine-based activation motifsITAMsAntigen receptorsResiduesInhibitorsLymphocytesPhosphorylateMotifPlasma membraneSignalsCatalyticLigandExtracellularMoleculeSubstratesCascadesINHIBITORMembraneImmunePhosphataseMediatesInitiatesIncluding Bruton's tyrosiCascadeDAP12GenesBecomes phosphorylatedCytoplasmic proteinLigationAdaptor proteinsPhosphorylation of tyrosineFusion ProteinsAdapterRegulatesMediateChemokine receptors
Spleen7
- ITAM phosphorylation leads to activation of spleen tyrosine kinase (Syk) and downstream signaling cascades (7). (cellsignal.com)
- This protein may bind zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. (genecards.org)
- Spleen tyrosine kinase (Syk) is involved in the development of the adaptive immune system and has been recognized as being important in the function of additional cell types, including platelets, phagocytes, fibroblasts, and osteoclasts, and in the generation of the inflammasome. (biomedcentral.com)
- By using this strategy, NFAT activating molecule 1 (NFAM1) was cloned as an immunoreceptor tyrosine-based activation motif (ITAM)-bearing cell surface molecule belonging to the Ig superfamily and is predominantly expressed in spleen B and T cells. (pnas.org)
- Inhibitors of tyrosine kinases expressed in lymphocytes, such as spleen tyrosine kinase and Janus kinase, are being tested in autoimmune diseases. (biomedcentral.com)
- Spleen tyrosine kinase (Syk) activation is a key intermediate step in the activation of platelets by the physiologic agonist collagen. (ashpublications.org)
- The phosphorylated ITAM domain recruits LYN proto-oncogene, Src family tyrosine kinase (Lyn) for phosphorylation, and the phosphorylation of Lyn activates spleen tyrosine kinase (Syk). (sciencebuzz.com)
Immunoreceptor tyrosine-based activation motifs6
- These activating receptors do not contain intrinsic kinase activity, but instead associate with transmembrane adaptor molecules containing immunoreceptor tyrosine-based activation motifs (ITAMs). (rupress.org)
- LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. (genecards.org)
- We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs). (asm.org)
- All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. (uniprot.org)
- These receptors consist of transmembrane ligand-binding subunits that are noncovalently associated with signaling subunits that contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domains (Fig. 1a). (schoolbag.info)
- In most analysed species, ITAM (immunoreceptor tyrosine-based activation motifs) or ITAM-like motif-containing proteins exist which contain Ig-V-like, ligand binding domains closely related to that of CEACAM1. (biomedcentral.com)
ITAMs8
- Phosphorylated ITAMs act as docking sites for Syk family tyrosine kinases (Syk in B cells and Zap-70 in T cells). (cellsignal.de)
- ITAMs are present in the cytoplasmic domains of several molecules that serve as signal transducers for immunoreceptors ( 1 - 5 ), including CD3 (γ, δ, ε, and ζ) for TCR, Igα/β for B cell antigen receptor (BCR), FcRγ for Fc receptors, and DAP12 for natural killer (NK) cell receptors. (pnas.org)
- ITAMs are an arrangement of two tyrosines in a peptide with a certain spacing between them. (antievolution.org)
- What makes ITAMs special is that there are proteins such as ZAP70 that contain dual SH2 domains and bind to the ITAM phosphorylated tyrosines as a unit. (antievolution.org)
- Upon engagement of ITAM-coupled receptors, an activation signal cascade is initiated with phosphorylation of specific tyrosines in ITAMs, culminating in the activation of transcription factors including NF-κB, nuclear factor-activated T cells (NFAT), and activating protein-1 (AP-1). (springer.com)
- Upon stimulation, the tyrosine residues within the ITAMs become phosphorylated, permitting the binding of SH2 domain-containing proteins. (asm.org)
- A primary role of the Src family kinases is to phosphorylate two tyrosine residues within the ITAMs of BCR and TCR. (asm.org)
- Thus, ITAMs function as a scaffold to recruit and organize effector molecules upon receptor ligation. (asm.org)
Antigen receptors3
- Stimulation of antigen receptors in T and B cells leads to the activation of the Src and Syk families of protein tyrosine kinases (PTK). (rupress.org)
- Thus, the lymphocyte antigen receptors use similar models of membrane-bound antigen receptors linked to signal-transducing accessory chains. (cellsignal.de)
- Chimeric antigen receptors (CAR) bearing an antigen-binding domain linked in cis to the cytoplasmic domains of CD3ζ and costimulatory receptors have provided a potent method for engineering T-cell cytotoxicity toward B-cell leukemia and lymphoma. (aacrjournals.org)
Residues12
- Tyr525 and Tyr526 are located in the activation loop of the Syk kinase domain and phosphorylation at these residues (equivalent to Tyr519/520 of mouse Syk) is essential for Syk function (8). (cellsignal.com)
- PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. (umbc.edu)
- Following engagement of TCR, the Zap70 undergoes phosphorylation on multiple tyrosine residues that are implicated in the regulation of its catalytic activity and interaction with signaling effector molecules downstream of the TCR. (jimmunol.org)
- Among the earliest detectable effects in engaged T cells are the phosphorylation of multiple cellular substrates on tyrosine residues, including the cytoplasmic tails of the TCR subunits ( 3 , 4 , 5 ). (jimmunol.org)
- The reversible phosphorylation of serine, threonine, and tyrosine residues directly controls many cellular processes, leading to the activation of a coordinated network of additional phosphorylation events across multiple proteins over time. (mcponline.org)
- The ITAM motif is based on four residues. (antievolution.org)
- Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding of SH2-containing proteins. (asm.org)
- The 10 copies of this motif within the cytoplasmic domains of the TCR:CD3 complex become phosphorylated on the conserved tyrosine residues when the TCR: peptide(MHC) interaction occurs, this allows a docking site for adaptor molecules which cause the mitogenic effects which result in polyclonal T-cell expansion. (careersuccessions.com)
- chain, this additional docking results in receptor clustering (Lipid raft) which promotes the recruitment of signalling proteins such as the Linker protein of Activated T-cells (LAT), this becomes phosphorylated by ZAP-70, these phosphorylated tyrosine residues become docking sites for enzymes bearing Sh2 domains which will subsequently cause the downstream signalling to occur. (careersuccessions.com)
- A cholesterol-regulated Protein phosphatase 2A ( PP2A catalytic )/ Protein tyrosine phosphatase, non-receptor type 7 ( HePTP ) complex dephosphorylates both the phosphotyrosine and the phosphothreonine residues in the activation loop of ERK1/2 due to the combined activities of the serine/threonine phosphatase PP2A catalytic and the tyrosine phosphatase HePTP [ 3 ]. (bio-rad.com)
- All isoforms of FcγRII (A, B and C) bind the Fc domain of IgG via a highly conserved extracellular domain and rely on phosphorylation of their conserved, cytoplasmic tyrosine residues for signal generation. (biologists.org)
- two conserved tyrosine residues of FcγRIIA/C are arranged in a so-called immunoreceptor tyrosine-based activation motif (ITAM). (biologists.org)
Inhibitors9
- This blockage is associated with impaired phosphorylation of Syk, Vav1, JNK, and p38, which mimics data obtained using inhibitors of the src-family kinases (SFK). (rupress.org)
- This invention relates to inhibitors of the family tyrosine kinase, and particularly, inhibitors of Bruton's Tyrosine Kinase (BTK). (google.com)
- Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. (readbyqxmd.com)
- The Src family kinase inhibitors prevented Syk phosphorylation and its ubiquitination, indicating that the process is downstream of Src kinases. (ashpublications.org)
- The ubiquitination of Syk did not cause degradation of the protein as evidenced by the lack of effect of proteasomal and lysosomal inhibitors. (ashpublications.org)
- Using samples from patients with CLL, we compared the effects of both BTK inhibitors on biologic activity, chemokine production, cell migration, BTK phosphorylation, and downstream signaling in primary CLL lymphocytes and on normal T-cell signaling to determine the effects on other kinases. (aacrjournals.org)
- Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCθ are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCθ in both Th1 and Th2 development. (biomedcentral.com)
- The similar reduction of FcγRII cap formation correlated with inhibition of receptor phosphorylation was achieved with the use of PP1 and herbimycin A, specific inhibitors of Src family tyrosine kinases. (biologists.org)
- Several factors, including the immunoglobulin heavy-chain variable region gene ( IGHV ) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. (medicalcases.info)
Lymphocytes8
- The T-cell receptor , or TCR , is a molecule found on the surface of T cells , or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. (wikipedia.org)
- Signaling by the antigen receptor of T lymphocytes initiates different developmental transitions, each of which require the tyrosine kinase ZAP70. (embopress.org)
- Here, in naive T lymphocytes, we compare the signaling capacities of the ζ and γ subunits within single-chain variable domain (scFv) chimeric receptors recognizing the carcinoembryonic Ag (CEA). (jimmunol.org)
- Indeed lymphocytes lacking CD45 show significant hyporesponsiveness to antigen receptor cross-linking attributed to a failure to appropriately activate SFK ( 29 ). (rupress.org)
- Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. (springer.com)
- In contrast, off-target effects on SRC-family kinases were more pronounced with ibrutinib than acalabrutinib in healthy T lymphocytes. (aacrjournals.org)
- Key words: self-tolerance, T cell receptor, B cell receptor, autoimmunopathogenesis, apoptosis Introduction T lymphocytes are credited with determining the functional outcome of immune responses and form important components of the adaptive immune system. (healthdocbox.com)
- Most of the cytokine receptors whose ligands regulate proliferation and differentiation in the hematopoietic and some hormones as well as the antigen-specific receptors on T- and B-lymphocytes fall into a class of heterogenous receptors that lack an obvious catalytic domain. (healthdocbox.com)
Phosphorylate1
- receptors phosphorylate reviewed in download Инструкция по взаимодействию и технология работы членов экипажа самолета Ил 76 (Ил 76Т) sites against extracellular significant genes. (familie-walther.eu)
Motif12
- This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. (genecards.org)
- Each of these polypeptides contains at least one immunoreceptor tyrosine-based activation motif (ITAM) (2). (cellsignal.com)
- These data, supported by analogous findings after CD16 and NKG2D stimulation of CD45 −/− primary NK cells, place CD45 upstream of SFK in NK cells after stimulation via immunoreceptor tyrosine-based activation motif-containing receptors. (rupress.org)
- Analysis of sequence elements responsible for the signaling properties of the transducing subunits of BCR and TCR has led to the identification of the immunoreceptor tyrosine-based activation motif (ITAM) ( 3 , 8 , 36 , 37 ). (asm.org)
- These observations provide the first direct evidence of an essential role for the immunoreceptor tyrosine‐based activation motif (ITAM) in signalling by a non‐immune receptor stimulus. (embopress.org)
- Syk assembles into signalling complexes at the plasma membrane via interaction between its tandem Src homology 2 (SH2) domains and a tyrosine‐phosphorylated immunoreceptor tyrosine‐based activation motif (ITAM). (embopress.org)
- 9-11 Initially the immunoreceptor tyrosine-based activation motif (ITAM) of the FcRγ-chain becomes phosphorylated by an Src family kinase, Fyn and/or Lyn. (ashpublications.org)
- Protein tyrosine phosphatase receptor type ( RPTPRR ) and Protein tyrosine phosphatase non-receptor type 5 ( STEP ) retain ERK1/2 in the cytoplasm in an inactive form by association through a kinase interaction motif and tyrosine dephosphorylation. (bio-rad.com)
- The conformational changes of Igα and Igβ lead to the phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM) domains of Igα and Igβ. (sciencebuzz.com)
- This receptor complex serves to link CD36 to the adaptor FcRγ, which bears an immunoreceptor tyrosine activation motif. (pubmedcentralcanada.ca)
- Human CEACAM3 is one such protein which can function as a CEACAM1 decoy receptor in granulocytes by mediating the uptake and destruction of specific bacterial pathogens via its ITAM-like motif. (biomedcentral.com)
- In addition, the repetitive sequences within gene families enhance the probability of recombination which can change the function of a gene dramatically within a short period of time through, for example, the exchange of cytoplasmic signalling motif-coding regions of transmembrane protein genes. (biomedcentral.com)
Plasma membrane8
- Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. (abcam.com)
- This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. (nih.gov)
- We show that the T-cell antigen receptor (TCR) and a protein tyrosine kinase, Lck, have a patchy plasma membrane distribution in Jurkat T cells at reduced temperatures, although they have a continuous distribution at physiological temperature (37°C). GM1 displays a patchy distribution at reduced temperature after Triton X-100 extraction. (biologists.org)
- Receptors on the plasma membrane of phagocytes can be divided into nonopsonic or opsonic receptors. (hindawi.com)
- These cells abundantly express FcεRI (~200,000 receptors per cell) at the plasma membrane, where they bind allergen-specific IgE with high affinity (K D ~ 10 -10 M) (2), sensitizing the cell and priming it to respond rapidly during subsequent exposure. (schoolbag.info)
- The activation of both BCR and T cell receptor (TCR) induces the dephosphorylation of ezrin-radixin-moesin (ERM) proteins that are the linkers between the plasma membrane and the actin cytoskeleton and induces the detachment of ERM from the actin cytoskeleton [21- (sciencebuzz.com)
- Lyn was displaced from DRMs under the influence of DL-α-hydroxymyristic acid and 2-bromopalmitic acid, agents blocking N-terminal myristoylation and palmitoylation of proteins, respectively, and after disruption of DRM integrity by depletion of plasma membrane cholesterol withβ -cyclodextrin. (biologists.org)
- On the other hand, the actin cytoskeleton in monocytic cells can also serve as a driving force for translocation of FcγRII clusters (patches) in the plane of the plasma membrane and subsequent assembly of receptor caps ( Kwiatkowska and Sobota, 1999b ). (biologists.org)
Signals11
- The TCRαβ dimer recognizes antigenic peptides, while the associated signaling chains transduce signals with their cytoplasmic ITAM domains. (cellsignal.de)
- Immunoreceptors such as T-cell receptors (TCRs), B-cell receptors (BCRs), some members of Fc receptors (FcRs), and activating NK receptors (NKRs) transduce activation signals by associating with signaling chains (e.g. (springer.com)
- These results demonstrate that the KSHV transforming protein K1 contains a functional ITAM in its cytoplasmic domain and that it can transduce signals to induce cellular activation. (asm.org)
- Activation of mouse platelets by collagen is associated with tyrosine phosphorylation of multiple proteins including the Fc receptor γ‐chain, the tyrosine kinase Syk and phospholipase Cγ2, suggesting that collagen signals in a manner similar to that of immune receptors. (embopress.org)
- B-cell receptor (BCR) signals promote survival of chronic lymphocytic leukemia (CLL) cells, and it is believed that overexpressed and constitutively active Lyn mediates this signaling. (aacrjournals.org)
- When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. (uniprot.org)
- Phosphorylated CD19 activates PI3K by binding to the p85 subunit of PI3K and produce phosphatidylinositol-3,4,5-trisphosphate (PIP3) from PIP2, and PIP3 transmits signals downstream . (apexbt.com)
- At the cellular level, these strategies involve a large array of receptors (TLRs) and sensors ( STING axis and inflammasomes ) that induce inflammatory signals and antigen clearance. (cisbio.com)
- Integrins also play a major role in T-cell activation by providing co-stimulatory signals that synergize with early signals initiated by the TCR (T-cell receptor). (biochemj.org)
- Therefore, Rictor is critical for B cell survival signals initiated via Phosphotidylinositol 3 kinase (PI3K) . (sciencebuzz.com)
- these rearrangements of the actin cytoskeleton help to transport clusters of T cell receptors to the center of the synapse and enable the T cell receptors to transmit signals that lead to the T cell being activated. (elifesciences.org)
Catalytic6
- Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa. (umbc.edu)
- The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). (umbc.edu)
- Zap-70 is a member of the Syk subfamily of kinases, which are cytoplasmic (or nonreceptor) tyr kinases containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. (umbc.edu)
- The transmembrane protein tyrosine phosphatase CD45 is expressed on all hematopoietic cells including NK cells and appears to function by dephosphorylating the COOH-terminal tyrosine of SFKs, leading to a conformation that favors autophosphorylation of the catalytic tyrosine ( 26 - 28 ). (rupress.org)
- PP2A catalytic dephosphorylates and blocks activation of both ERK1/2 and its upstream kinase, Mitogen-activated protein kinase kinase 1 ( MEK1(MAP2K1) ), determining the kinetics of MAPK cascades [ 4 ], [ 5 ]. (bio-rad.com)
- Cyclic-AMP-dependent protein kinase (composed of regulatory PKA-reg (cAMP-dependent) and catalytic PKA-cat (cAMP-dependent) subunits) phosphorylates HePTP reducing its binding to ERK1/2 which causes ERK1/2 release and activation [ 6 ]. (bio-rad.com)
Ligand8
- Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:9490415, PubMed:9655483, PubMed:10604985). (genecards.org)
- TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation (PubMed:9490415). (genecards.org)
- Chimeric receptors comprising the γ and ζ cytoplasmic signaling chains fused to an extracellular ligand-binding domain of a heterologous receptor or single-chain Ab have served as effective tools for elucidating and comparing the structure-function relationship of these TCR-ζ and Fc receptor for IgE (FcεRI)-γ subunits ( 11 , 12 , 13 ). (jimmunol.org)
- We have identified the Fyn- and SLP-76-associated protein Fyb/SLAP as a new ligand for Ena/ vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. (rupress.org)
- Emphasis is laid on the role of T and B cell receptor/ligand interactions, functions and malfunctions due to structural and quantitative alterations in T- B- cell cluster of antigen determinants. (healthdocbox.com)
- Using a combination of phosphoprotein isolation, mass spectrometry, super-resolution imaging and gene silencing we have determined that the receptor induces ligand internalization through a heteromeric complex consisting of CD36, β 1 and/or β 2 integrins, and the tetraspanins CD9 and/or CD81. (pubmedcentralcanada.ca)
- The resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. (pubmedcentralcanada.ca)
- Our analysis of the substitution rates within the nucleotide sequence which codes for the ligand binding domain of CEACAM1 indicates that the selection for diversification is, perhaps, a consequence of the exploitation of CEACAM1 by a variety of viral and bacterial pathogens as their cellular receptor. (biomedcentral.com)
Extracellular3
- How TREM2 contributes to disease function is currently an active area of research (4,5), but might drive a number of microglial cellular functions ranging from microgliosis, phagocytosis, and cytokine release via a variety of signaling cascades triggered by TREM2.The TREM2 receptor is a single-pass type I membrane glycoprotein that consists of an extracellular immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic tail. (cellsignal.com)
- Collagen is an abundant extracellular matrix protein present in blood vessel subendothelium. (embopress.org)
- TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). (biochemj.org)
Molecule5
- One molecule that may be subject to regulation by membrane proximity is the non‐receptor tyrosine kinase ZAP70, which has diverse roles in signaling by the antigen receptor. (embopress.org)
- In particular, we have cloned an ITAM + molecule, NFAM1 (NFAT activating molecule 1). (pnas.org)
- The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. (genecards.org)
- Studies with mutant Jurkat T cells implicate the Src family kinase Lck as the responsible enzyme and its activity in this process is influenced by the functional integrity of the downstream signaling molecule ZAP-70. (rupress.org)
- Some surface receptors such as G-protein-coupled receptors represent another class of molecule that can be inhibited by small-molecule compounds. (biomedcentral.com)
Substrates2
- The activated ZAP-70 phosphorylates several downstream substrates. (movd2016.org)
- The domains are frequently found as repeats in a single protein sequence and will then often bind both mono- and di-phosphorylated substrates. (embl-heidelberg.de)
Cascades2
- The subsequent induction of multiple downstream signaling cascades leads to cell activation and stimulation of critical biological effector functions such as cytolysis, cytokine release, and phagocytosis ( 8 , 10 , 11 ). (jimmunol.org)
- This initiates the activation of downstream signaling cascades, such as the activation of Brutons tyrosine kinase (Btk) and phospholipase C gamma 2 (PLCγ2) [1- (sciencebuzz.com)
INHIBITOR3
- MAP or ERK kinase (MEK) inhibitor U0126, p38 MAP kinase inhibitor SB203580, protein kinase C (PKC) inhibitor Bisindolylmaleimide I and phosphatidylinositol 3 kinase (PI3- kinase) inhibitor LY294002 were added to cell cultures. (ubc.ca)
- Protein tyrosine phosphatase receptor type E ( PTPR-epsilon ) is also a physiological inhibitor of ERK signaling by protecting cells from prolonged ERK1/2 activation in the cytosol [ 11 ]. (bio-rad.com)
- Ibrutinib is an oral, first-in-class Bruton tyrosine kinase (BTK) inhibitor that is approved by the US Food and Drug Administration for the treatment of patients with previously treated and untreated chronic lymphocytic leukemia (CLL). (aacrjournals.org)
Membrane17
- Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane. (wikipedia.org)
- The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. (genecards.org)
- The B cell receptor (BCR) is composed of a membrane-bound antibody (immunoglobulin or Ig) flanked by Igα/Igβ (CD79A/CD79B) heterodimers. (cellsignal.de)
- The T cell receptor (TCR) consists of a membrane-bound αβ heterodimer (TCRαβ), four CD3 chains (two CD3ε, one CD3γ, one CD3δ), and a ζ−chain homodimer. (cellsignal.de)
- Plexins are single membrane-spanning signaling proteins encompassing Plexin A1, A2, A3, and A4. (cellsignal.com)
- ZAP70 SH2 domains are not required for signaling when the kinase is artifically recruited to the membrane, indicating that the SH2 domains function solely in recruitment and not in kinase activation. (embopress.org)
- CARMA1 is a member of CARD-containing membrane-associated guanylate kinase (MAGUK) family and was found to be a binding partner of BCL10 via CARD-CARD interaction (Bertin et al. (springer.com)
- The membrane-binding domains of the 4.1 proteins are closely related, both in sequence and in structure, to the N-terminal domains of ezrin, radixin, and moesin (the ERM proteins), and are therefore commonly referred to as the FERM domains.15C17 Both 4.1 and ERM proteins bind to numerous transmembrane proteins through this domain name. (movd2016.org)
- ERM proteins regulate the linkage of cortical actin to membrane-associated proteins in cellular substructures by directly binding to both. (springer.com)
- The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. (springer.com)
- accessibility of TP53 at metabolism protein S46 mediates part of Professional irreversible vaults however than tyrosine membrane binding rafts. (evakoch.com)
- Stimulated changes in membrane architecture, which includes protein and lipid segregation within membranes as well as membrane trafficking, regulate these cellular responses. (schoolbag.info)
- Finally, we discuss cross-correlation microscopy methods, application of antigen-patterned surfaces, and fluorescence-based trafficking assays to study dynamics of stimulated proteins interactions and membrane trafficking. (schoolbag.info)
- In this article, we discuss molecular biology tools that are being applied to the study of protein trafficking and membrane compartmentalization. (schoolbag.info)
- We then conclude this article by discussing spectrofluorometric methods used to study protein colocalization and membrane trafficking in living cells. (schoolbag.info)
- Both soluble and membrane-bound antigens are recognized by the multichain immune recognition receptor (MIRR) family of antigen-binding receptors. (schoolbag.info)
- After crosslinking, FcγRII was found to be recruited to detergent-resistant membrane domains (DRMs), rafts, where it coexisted with Lyn kinase and underwent tyrosine phosphorylation. (biologists.org)
Immune11
- The triggering receptor expressed on myeloid cells 2 (TREM2) protein is an innate immune receptor that is expressed on the cell surface of microglia (3). (cellsignal.com)
- Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. (abcam.com)
- The direction and magnitude of an immune response are determined by the behavior of individual lymphocyte clones bearing distinct Ag receptors and their mutual interactions. (pnas.org)
- i'm not an expert on signal transduction, but it seems pretty clear that A74 is involved in immune-related signal transduction, and that tyrosine phosphorylation of the ITAM is part of it. (antievolution.org)
- Those receptors and sensors are shared among most unspecified immune cells including dendritic cells, macrophages, neutrophils, natural killer or mastocytes. (cisbio.com)
- This generates a diverse repertoire of antigen-specific receptors with varying specificities, this provides the versatility that is needed for the recognition of nearly all pathogens including altered self-cells seen in cancer and thus required for normal immune system functioning. (careersuccessions.com)
- The specificity of T-cell-mediated immune responses is dependent upon the T-cell receptor (TCR) on CD4 helper or CD8 cytotoxic T cells. (healthdocbox.com)
- Cells of the immune system detect and respond to the presence of foreign antigens by signaling through an array of receptors, which include the multichain immune recognition receptor (MIRR) family. (schoolbag.info)
- Immune cells express a variety of receptors to detect foreign antigens and respond in a selective manner to clear pathogens and infected cells from the body. (schoolbag.info)
- Immune cells known as T cells recognize infection through a protein on their surface known as the T cell receptor. (elifesciences.org)
- As part of the activation process, the T cell spreads over the surface of the cell that is displaying foreign proteins to form an extensive interface known as an immune synapse. (elifesciences.org)
Phosphatase2
- Ly49 receptors, upon tyrosine phosphorylation, are thought to recruit both Src homology 2-containing phosphatase 1 (SHP1) and Src homology 2 domain-containing inositol-5′-phosphatase (SHIP), whereas NK cell licensing is known to be SHP1-independent. (ubc.ca)
- Insights into the suppressor of T-cell receptor (TCR) signaling-1 (Sts-1)-mediated regulation of TCR signaling through the use of novel substrate-trapping Sts-1 phosphatase variants. (nih.gov)
Mediates4
- Also mediates cell activation through association with activating receptors of the CD200R family (By similarity). (genecards.org)
- Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). (abcam.com)
- Upon P58(IPK modification, receptor phosphorylation lipoprotein dimethylselenide( GM-CSFR), a motility of degradation( CSF2RA) and IL17( CSF2RB) mitosis, mediates a regulating syndrome that namely so mediates route, eco-friendliness and such dehydrogenase of fatty sterols but can post-transcriptionally promote complex turn into essential requirements and its protein via 3-like reactions. (evakoch.com)
- Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1. (readbyqxmd.com)
Initiates1
- This initiates a series of events which may involve other kinases and adapter proteins leading to tyrosine phosphorylation and activation of PLCγ2. (embopress.org)
Including Bruton's tyrosi1
- Phospho-Blnk acts as a scaffold for the assembly of the other components, including Bruton's tyrosine kinase (Btk), Vav 1, and phospholipase C-gamma 2 (PLCγ2) . (apexbt.com)
Cascade5
- Thus, ITAM represents a hallmark of signal modules that convert an Ag recognition event to initiate a signal cascade. (pnas.org)
- The computational model describes the behavior of the participants of the fucoidan receptor signaling cascade. (springer.com)
- and a sequential protein kinase cascade is initiated, consisting of MAP kinase kinase kinase (MAP3K), MAP kinase kinase (MAPKK), and MAP kinase (MAPK) . (apexbt.com)
- This recognition is achieved thanks to a variety of discrete receptors that distinguish the particle as a target and then initiate a signaling cascade that promotes phagocytosis. (hindawi.com)
- However, it is not known how patched FcγRII induces the signaling cascade(s) that control actin-driven capping of the receptor. (biologists.org)
DAP122
- Upon activation, TREM2 interacts with the tyrosine kinase-binding protein DNAX-activating protein 12 (DAP12, TYROBP) to form a receptor-signaling complex (6). (cellsignal.com)
- In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. (readbyqxmd.com)
Genes4
- This domain occurred 378 times on human genes ( 858 proteins). (umbc.edu)
- Appearance and disappearance of Syk family protein-tyrosine kinase genes during metazoan evolution. (antievolution.org)
- 1. the RAG genes and RSSs were originally a transposon, and the RAG proteins had transposase activity. (antievolution.org)
- The STimulator of INterferon Genes (STING), is a cytoplasmic protein that teams up with the cytoplasmic DNA sensor cGAS to detect floating dsDNA from pathogens or shrinking mitochondria and initiate a signal transduction via TBK1, IRF3 and NF-kB to promote the expression of pro-inflammatory mediators and type 1 IFNs (TNF-a, IFN- a, IFN- b). (cisbio.com)
Becomes phosphorylated1
- Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. (genecards.org)
Cytoplasmic protein1
- Clone REA111 recognizes Syk, a 72 kDa non-receptor tyrosine kinase cytoplasmic protein. (miltenyibiotec.com)
Ligation1
- TCR ligation also induces a conformational change in CD3ε, such that a proline region is exposed and then associates with the adaptor protein Nck (5). (cellsignal.com)
Adaptor proteins1
- The DD is important for transducing the death signal by recruiting other DD containing adaptor proteins (FADD, TRADD, RIP) to the death-inducing signaling complex (DISC), resulting in activation of caspases. (cellsignal.com)
Phosphorylation of tyrosine1
- The BCR-mediated phosphorylation of ezrin negatively regulates activation events such as the phosphorylation of tyrosine kinases . (sciencebuzz.com)
Fusion Proteins2
- DNA Constructs and Fusion Proteins. (rupress.org)
- created transgenic mice that portrayed a soluble type II TGF receptor:Fc fusion proteins (Fc:TRII) in order from the mammary gland-selective mouse mammary tumor pathogen (MMTV) promoter/enhancer. (angiogenesis-blog.com)
Adapter1
- The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. (abcam.com)
Regulates1
- Bone of TP53( protein) at the green fibril vertebrates S15 and S20 allows a Many number in session receptor as control at these polymerases regulates with signaling of the formin transmembrane MDM2 to TP53. (evakoch.com)
Mediate1
- Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. (readbyqxmd.com)
Chemokine receptors1
- These co-receptors are chemokine receptors CCR5 or CXCR4. (wikipedia.org)