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.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.Genes, T-Cell Receptor: DNA sequences, in cells of the T-lymphocyte lineage, that code for T-cell receptors. The TcR genes are formed by somatic rearrangement (see GENE REARRANGEMENT, T-LYMPHOCYTE and its children) of germline gene segments, and resemble Ig genes in their mechanisms of diversity generation and expression.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.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.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.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.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.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.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.Receptors, Antigen, T-Cell, alpha-beta: T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.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.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Gene Rearrangement, beta-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.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.Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors.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.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.Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.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.Genes, RAG-1: Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.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.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.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.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 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.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.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)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.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.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.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.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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 Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).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.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.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.Lactams, Macrocyclic: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.Receptors, Antigen, T-Cell, gamma-delta: T-cell receptors composed of CD3-associated gamma and delta polypeptide chains and expressed primarily in CD4-/CD8- T-cells. The receptors appear to be preferentially located in epithelial sites and probably play a role in the recognition of bacterial antigens. The T-cell receptor gamma/delta chains are separate and not related to the gamma and delta chains which are subunits of CD3 (see ANTIGENS, CD3).Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Genes, Immunoglobulin: Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).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.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.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.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.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.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.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.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.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.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 enzymesKinetics: The rate dynamics in chemical or physical systems.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.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.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.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).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.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.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).Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.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.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.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.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.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.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.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.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.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.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.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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).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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Leukemia, Lymphoid: Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.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.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.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.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.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.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Mice, Inbred C57BLImmunoblotting: 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.Pre-B Cell Receptors: Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.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.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.Leukemia: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)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.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.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.Benzamides: BENZOIC ACID amides.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.PiperazinesReceptor, 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.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.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.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.Janus Kinase 1: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.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.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).Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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)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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.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.Cell Adhesion: Adherence of cells to surfaces or to other cells.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.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.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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.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.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.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.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.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.Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.QuinazolinesFusion 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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)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.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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 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.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.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.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.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.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.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.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.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.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.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.Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.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.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.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.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.
The trk proto-oncogene encodes a receptor for nerve growth factor
musk - muscle, skeletal receptor tyrosine-protein kinase isoform X2 - Scleropages formosus (Asian bonytongue) - musk gene &...
N307 07611 - Receptor protein-tyrosine kinase - Dryobates pubescens (Downy woodpecker) - N307 07611 gene & protein
Genetic Analysis of the Caenorhabditis elegans MAP Kinase Gene mpk-1 | Genetics
Patente US6359115 - Human receptor tyrosine kinase, KDR - Google Patentes
A novel putative tyrosine kinase receptor encoded by the eph gene | Science
Lenti-Her2 T cell receptor (G3) Viral Particle vector - Creative Biolabs
Lenti-HER2 T cell receptor (HER2-1) Viral Particle vector - Creative Biolabs
KDR Mouse anti-Human, Clone: OTI2A1, lyophilized, TrueMAB 100 µg;
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β amyloid protein precursor-like (Appl) is a Ras1/MAPK-regulated gene required for axonal targeting in Drosophila photoreceptor...
Advances in molecular, genetic and immune signatures of gastric cancer: Are we ready to apply them in our patients' decision...
JCI -
LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors
Human Antibodies - Volume 10, issue 3-4 - Journals - IOS Press
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A Novel Stat3 Binding Motif in Gab2 Mediates Transformation of Primary Hematopoietic Cells by the Stk/Ron Receptor Tyrosine...
Anaplastic lymphoma kinase activity is essential for the proliferation and survival of anaplastic large-cell lymphoma cells |...
Notch Signaling Regulates Platelet-Derived Growth Factor Receptor-β Expression in Vascular Smooth Muscle Cells | Circulation...
MutationsProliferationPathwayDifferentiationPhosphatasesSurvivalInhibitorsExpressionPI3KInteractionsActivityPhosphorylationMitogen-activaIntracellularPhosphatidylinositol-3 kinaAntigenSubfamilySignal transductionAngiogenesisProto-oncogene tyrosine-protein kinase SrcDimerizationCytoplasmic domainPutativeIsoformVascularVEGFRSurface receptorErbBSolubleAntibodiesVariantsAffinityType III receptor tyrosiAmplificationGrowth factor rAssaysFamily of protein tyrosinGrb2Anaplastic lymphoAdaptorTargetsSignalingNeurotrophicOverexpressionMoleculesEpidermal growthInteractHuman genomeVEGFR2Endothelial cells
Mutations4
- (2012) . Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. (icr.ac.uk)
- UNLABELLED: Activation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM) occurs through mutations or deletions in the extracellular (EC) domain. (icr.ac.uk)
- Gain-of-function mutations can increase the activity of an oncogene, and loss-of-function mutations may silence a tumor suppressor gene. (biomedcentral.com)
- It should be emphasized that the high level of somatic mutations that arise in IGHV in the germinal centre are a natural part of affinity maturation of antibodies and, unlike mutations in other genes, are not pathological. (medicalcases.info)
Proliferation3
- The serine-threonine kinase AKT regulates proliferation and survival by phosphorylating a network of protein substrates. (icr.ac.uk)
- Protein tyrosine phosphatases (PTPs) play an important role in regulating cell signaling events in coordination with tyrosine kinases to control cell proliferation, apoptosis, survival, migration, and invasion. (biomedcentral.com)
- Tyrosine phosphorylation has a crucial role in the regulation of physiological processes such as cell proliferation, differentiation, adhesion, and migration, which are closely relevant to human diseases, especially cancer. (biomedcentral.com)
Pathway1
Differentiation2
- These subsets are distinguished by whether CLL cells express an unmutated or mutated immunoglobulin heavy-chain variable region gene ( IGHV ), reflecting the stage of normal B cell differentiation from which they originate 1 , 2 . (medicalcases.info)
- CLL cells that express an unmutated IGHV originate from a B cell that has not undergone differentiation in germinal centres, which are the sites in the lymph nodes where B cells experience somatic hypermutation in their immunoglobulin variable region genes and selection during an immune response. (medicalcases.info)
Phosphatases2
- Receptor-type protein tyrosine phosphatases (PTPRs) are a subgroup of PTPs that share a transmembrane domain with resulting similarities in function and target specificity. (biomedcentral.com)
- Signaling pathways are coordinately controlled by a balance between activators, such as protein tyrosine kinases (TKIs), and inactivators, including protein tyrosine phosphatases (PTPs). (biomedcentral.com)
Survival3
- Cancer cells depend on a finite number of critical signals for their survival. (icr.ac.uk)
- A kinase-independent function of AKT promotes cancer cell survival. (icr.ac.uk)
- An AKT kinase domain mutant found in human melanoma (G161V) lacked enzymatic activity in vitro and in AKT1/AKT2 double knockout cells, but promoted growth factor independent survival of primary human melanocytes. (icr.ac.uk)
Inhibitors2
- ATP-competitive AKT inhibitors failed to block the kinase-independent function of AKT, a liability that limits their effectiveness compared to allosteric AKT inhibitors. (icr.ac.uk)
- 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)
Expression2
- We hypothesized that IQGAP1 could regulate TJ formation by modulating the expression and/or localization of junctional proteins, and we systematically tested this hypothesis in the model Madin-Darby canine kidney (MDCK) cell line. (icr.ac.uk)
- Genetic and epigenetic alterations such as copy number changes, mutation, and promoter methylation contribute to the expression level and/or function of PTPR proteins. (biomedcentral.com)
PI3K1
- In cancer cells harboring gain-of-function alterations in MET, HER2, or Phosphatidyl-Inositol-3-Kinase (PI3K), catalytically inactive AKT (K179M) protected from drug induced cell death in a PH-domain dependent manner. (icr.ac.uk)
Interactions1
- Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. (medicalcases.info)
Activity1
Phosphorylation27
- Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation. (wikipedia.org)
- The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. (wikipedia.org)
- Addition of NGF to PC12 cells elicits rapid phosphorylation of gp140trk on tyrosine residues and stimulates its tyrosine kinase activity. (nih.gov)
- The intracellular C terminal region displays the highest level of conservation and comprises catalytic domains responsible for the kinase activity of these receptors, which catalyses receptor autophosphorylation and tyrosine phosphorylation of RTK substrates. (wikipedia.org)
- The phosphorylation of specific tyrosine residues within the activated receptor creates binding sites for Src homology 2 (SH2) domain- and phosphotyrosine binding (PTB) domain-containing proteins. (wikipedia.org)
- Phosphorylation and activation of these two proteins on receptor binding lead to the initiation of signal transduction pathways. (wikipedia.org)
- Inhibition of NPM-ALK phosphorylation in the ALK + ALCL-derived cell lines resulted in significant inhibition of cell proliferation and induction of apoptotic-cell death, while having marginal effects on the proliferation and survival of K562, an ALK - leukemia cell line. (bloodjournal.org)
- Although the precise physiologic function and regulation of ALK have not been well defined, the NPM-ALK fusion gene encodes for an 80-kDa NPM-ALK chimeric oncoprotein with constitutively active ALK tyrosine kinase activity, which plays a key role in lymphomagenesis by the aberrant phosphorylation of multiple intracellular substrates downstream of NPM-ALK. (bloodjournal.org)
- PDGF-receptor activation was determined by phosphorylation analysis and inhibition studies using the PDGF-receptor tyrosine kinase inhibitor AG1296. (arvojournals.org)
- The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by CSK. (wikipedia.org)
- The antibody blocks EGFR activation by preventing tyrosine kinase-mediated phosphorylation of the protein ( 9 ). (spandidos-publications.com)
- This response was characterized by transient phosphorylation of extracellular signal-related kinase (ERK) and Akt (protein kinase B [PKB]), lack of activation of c-JUN NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and variable activation of phospholipase Cγ2 (PLCγ2) and nuclear factor-κB (NF-κB). (bloodjournal.org)
- In normal B cells, stimulation of the BCR leads to phosphorylation of immuno-receptor tyrosine-based activation motifs within the cytoplasmic tails of Igα and Igβ. (bloodjournal.org)
- Here we show that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on tyrosine of gp145trkB, one of the receptors encoded by trkB. (nih.gov)
- Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement. (merckmillipore.com)
- Signal-mediated activation of membrane receptor-kinases leads to auto-phosphorylation of the receptor on tyrosine residues. (highveld.com)
- The phosphorylated tyrosine is recognized by the SH2 domain of STAT, which then becomes activated via phosphorylation by JAK protein kinases. (highveld.com)
- Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. (nih.gov)
- This phosphorylation triggers recruitment of a range of adaptor proteins, such as Src homology 2 domain containing (SHC) protein and growth factor receptor-bound protein 2 (GRB2), followed by activation of a series of intracellular signaling cascades that affect cell proliferation, apoptosis, invasion, metastasis, and angiogenesis. (aacc.org)
- These include phosphorylation of phospholipase C gamma 1(PLCG) and subsequent hydrolysis of phosphatidylinositol 4,5 biphosphate (PIP2) into inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), which results in activation of protein kinase C (PRKC). (aacc.org)
- The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. (bio-rad.com)
- Activation of this receptor leads to tyrosine phosphorylation of JAK1 and TYK2 kinases. (wikidoc.org)
- Lyn up/up B cells are characterized by the constitutive phosphorylation of negative regulators of B cell antigen receptor (BCR) signaling including CD22, SHP-1, and SHIP-1, and display attributes of lymphocytes rendered tolerant by constitutive engagement of the antigen receptor. (rupress.org)
- However, exaggerated positive signaling is also apparent as evidenced by the constitutive phosphorylation of Syk and phospholipase Cγ2 in resting Lyn up/up B cells. (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)
Mitogen-activa5
- Differentiation of photoreceptors in the Drosophila compound eye requires activation of Ras1 and mitogen-activated protein kinase (MAPK) downstream of a receptor tyrosine kinase (RTK). (biologists.org)
- Fibroblast growth receptor 1, platelet-derived growth factor receptor-α, and epidermal growth factor receptor are all potential entry points to the phosphatidylinositol 3-kinase and mitogen-activated protein kinase intracellular signaling pathways already known to be important for neoplasia. (pnas.org)
- Additionally, using a molecular genetic approach, we determined that inhibitory forms of p42 mitogen-activated protein kinase and an Ets-2 transcription factor interfere with both the Ras and the Raf activation of the rat prolactin promoter. (asm.org)
- Among the many important signaling cascades induced by MET receptor activation are the phosphatidylinositol-3-kinase (PI3K)/Akt and the RAS/mitogen-activated protein kinase (MAPK) pathways. (onclive.com)
- 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)
Intracellular16
- The activated receptor as a result then becomes autophosphorylated on multiple specific intracellular tyrosine residues. (wikipedia.org)
- 2. A purified protein fragment which is an intracellular portion of a human KDR protein, comprising from about amino acid 790 to about amino acid 1356 as set forth in SEQ ID NO: 2, wherein position 848 is a valine residue. (google.es)
- 3. A purified protein fragment which is an intracellular portion of a human KDR protein, comprising from about amino acid 790 to about amino acid 1356 as set forth in SEQ ID NO: 2, wherein position 772 is an alanine residue, position 787 is an arginine residue, position 835 is a lysine residue, position 848 is a valine residue and position 1347 is a serine residue. (google.es)
- The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encoding human KDR, a DNA fragment encoding the intracellular portion of KDR, a DNA fragment encoding the extracellular portion of KDR with or without a membrane anchor sequence, substantially purified forms of associated human KDR, and human mutant forms of KDR. (google.es)
- In addition, we analyse the function of different intracellular proteins encoded by genes mutated or linked to PD. (plymouth.ac.uk)
- The α-chain is extracellular, whereas the β-chain traverses the cell membrane and contains the intracellular tyrosine kinase ( 1 ). (aacrjournals.org)
- The intracellular C-terminal region comprises domains responsible for the [[kinase]] activity of these receptors. (wikidoc.org)
- 13 - 16 Activation of PLCγ2 leads to the release of intracellular Ca 2+ and activation of protein kinase C (PKC), which are crucial for the activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-JUN NH 2 -terminal kinase (JNK), and p38 MAPK, and transcription factors, including nuclear factor-κB (NF-κB) and nuclear factor of activated T cells (NFAT). (bloodjournal.org)
- ROS1 is localized to the cell plasma membrane and contains both extracellular and intracellular domains. (atlasgeneticsoncology.org)
- Many of the RTK-effector protein interactions depend on the autophosphorylation of specific tyrosine residues in the intracellular carboxyl terminus of an RTK. (aspetjournals.org)
- These proteins normally function by activating various intracellular pathways in response to binding a specific signaling molecule, which at the time was unknown for fms . (xconomy.com)
- Silencing YAP or TAZ substantially reduced the amount of intracellular glutamate through decreased expression of SLC1A5 and GLS , respectively, genes that encode proteins that promote glutamine uptake and metabolism. (sciencemag.org)
- Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. (merckmillipore.com)
- The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. (nih.gov)
- Gene amplification and over-expression of the Erb family of receptors (EGFR and ErbB2) has been observed in breast, lung, and colorectal cancers, while the deregulated activation of intracellular mitogenic signaling has been implicated in many other cancers. (aacc.org)
- The sevenless locus encodes a transmembrane receptor molecule that contains an intracellular protein tyrosine kinase domain. (searlescholars.net)
Phosphatidylinositol-3 kina3
- In highly differentiated adenocarcinomas the ErbB2/ErbB3 complex is activated, which is followed by phosphatidylinositol 3-kinase (PI3K) activation. (cancerindex.org)
- Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. (nih.gov)
- Following activation of the EGFR pathway, the phosphatidylinositol 3-kinase (PI3K/AKT) pathway induces the major cellular survival and anti-apoptosis signals by stimulating nuclear transcription factors such as NFKB. (aacc.org)
Antigen7
- 1 , 2 Anaplastic large-cell lymphomas (ALCLs) comprise a group of non-Hodgkin lymphomas (NHLs) that are usually of T-cell origin and often present with extranodal disease, especially the skin, and are characterized by the expression of the CD30/Ki-1 antigen. (bloodjournal.org)
- However, studies using antigen-specific TCR transgenic mice, in which most of the CD4 cells remain in na?ve state throughout existence, possess pointed to intrinsic age-related defects in the function of na?ve CD4 Capital t cells (Linton 1996). (exposed-skin-care.net)
- Here we statement tests designed to test whether a related approach could improve the function of Capital t cells in vivo after adoptive transfer of CD4 cells to antigen-primed sponsor. (exposed-skin-care.net)
- Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. (nih.gov)
- SwissProt: O43561 # Required for TCR (T-cell antigen receptor)- and pre-TCR- mediated signaling, both in mature T-cells and during their development. (merckmillipore.com)
- These studies were at the frontier of cell biology, immunology and virology and centered on how these viruses prevent the surface expression of MHC class I and hence block antigen presentation. (herpesvirusworkshop.com)
- For example, mice with altered dosages of genes encoding B cell inhibitory and costimulatory receptors such as CD22, PD-1, FcγRIIb1, and CD19, all of which play key roles in modulating the strength of the B cell antigen receptor (BCR) * signal, are predisposed to autoimmune disease ( 2 - 8 ). (rupress.org)
Subfamily6
- The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. (nih.gov)
- The insulin receptor (IR) belongs to a subfamily of receptor tyrosine kinases that includes the insulin-like growth factor (IGF) 1receptor(IGF-1R) and the insulin-receptor-related receptor. (plos.org)
- This protein belongs to a subfamily of tyrosine kinase receptors with a homology region to the Dictyostelium discoideum protein discoidin I in their extracellular domain. (abnova.com)
- This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. (nih.gov)
- EphA1 is the founding member of what is recognised as the largest subfamily of the receptor tyrosine kinases. (atlasgeneticsoncology.org)
- The protein encoded by this gene is a receptor protein tyrosine kinase and type I transmembrane protein that belongs to the ROR subfamily of cell surface receptors. (xenbase.org)
Signal transduction7
- These results indicate that gp140trk is a functional NGF receptor that mediates at least some of the signal transduction processes initiated by this neurotrophic factor. (nih.gov)
- A subgroup of these kinases lack detectable catalytic tyrosine kinase activity but retain roles in signal transduction. (bio-rad.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)
- P rotein kinases are key modulators of signal transduction and play essential roles in the regulation of cell cycle, cellular movement, apoptosis, and other processes that are fundamental to the development and progression of cancers ( 1 ). (pnas.org)
- The phosphorylated regions of the receptor act as binding sites for a range of signal transduction proproteins. (onclive.com)
- The ultimate goal of all of these experiments is eventually to understand the biochemical steps of signal transduction by sevenless and other protein tyrosine kinases. (searlescholars.net)
- Janus kinase 3 ( JAK3 ) is a gene that encodes a protein-tyrosine kinase that functions in receptor-mediated signal transduction and is highly expressed in immune cells. (mycancergenome.org)
Angiogenesis7
- A major regulator of angiogenesis is VEGF and its cognate receptor VEGFR2. (hindawi.com)
- Angiopoietins are proteins with important roles in vascular development and angiogenesis. (wikipedia.org)
- Mitogens promote embryonic vascular development, growth, repair and angiogenesis in these cells. (google.es)
- The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. (antibodies-online.com)
- However, MET receptor signaling plays a particularly important role in coordinating cell motility, invasion, and angiogenesis (the formation of new blood vessels), and plays a very active part in the development of the embryo and in the formation of organs during early human development. (onclive.com)
- As part of this program, MET receptor activation promotes angiogenesis and aids in cancer cell invasion. (onclive.com)
- Fibroblast Growth Factors (FGFs) comprise a family of at least eighteen structurally realted proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentation, angiogenesis, wound healing and tumorgenesis. (prospecbio.com)
Proto-oncogene tyrosine-protein kinase Src1
- Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src or simply c-Src , is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. (wikipedia.org)
Dimerization3
- Dimerization leads to a rapid activation of the protein's cytoplasmic kinase domains, the first substrate for these domains being the receptor itself. (wikipedia.org)
- There are 7 families of mammalian STATs, all of which share an N-terminal domain involved in dimerization, a coiled-coil domain involved in protein-protein interactions, a DNA-binding domain, and a C-terminal SH2 domain. (highveld.com)
- For all these capsids, multiple levels of inter major capsid protein (MCP) interactions-six sets of stacked hairpins lining the hexon channel, disulfide bonds across channel and buttress domains in neighboring MCPs, and an interaction network forged by the N-lasso domain and secured by the dimerization domain-define a robust capsid that is amenable to the tremendous pressure exerted by the enclosed genome. (herpesvirusworkshop.com)
Cytoplasmic domain1
- This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. (genecards.org)
Putative6
- In this study, a novel putative kinase receptor gene, termed eph, has been identified and characterized by molecular cloning. (sciencemag.org)
- Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. (genecards.org)
- Hirai H, Maru Y, Hagiwara K, Nishida J, Takaku F. A novel putative tyrosine kinase receptor encoded by the eph gene. (springer.com)
- In Caenorhabditis elegans , 10 putative ionotropic glutamate receptor subunits have been identified, a surprising number for an organism with only 302 neurons. (jneurosci.org)
- The Dictyostelium genome contains one putative CBF-A gene and one putative CBF-B gene. (highveld.com)
- The other, Son of sevenless ( Sos ), encodes a putative guanine nucleotide exchange factor that may function to stimulate the activity of the Ras1 protein. (searlescholars.net)
Isoform8
- This triple mutant strain carries a humanized ApoE knock-in mutation (sequence coding for isoform E4), a CRISPR/cas9-generated 94bp deletion in exon 14 of the App gene and a CRISPR/cas9-generated R47H point mutation of the Trem2 gene. (jax.org)
- The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. (jax.org)
- The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16. (jax.org)
- Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. (origene.com)
- One isoform lacks the intermembrane region and is secreted outside the cell. (ucsc.edu)
- Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. (nih.gov)
- Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. (nih.gov)
- A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. (prospecbio.com)
Vascular13
- In the renal glomeruli, podocytes express vascular endothelial growth factor (VEGF), whereas VEGF receptor tyrosine kinases are expressed by both podocytes and glomerular endothelial cells [ 3 ]. (hindawi.com)
- The increased risk of vascular events observed among elderly patients with chronic myeloid leukaemia, compared with patients without cancer, may not be driven by tyrosine kinase inhibitor therapy, US researchers suggest. (news-medical.net)
- Vascular endothelial cells form a luminal non-thrombogenic monolayer throughout the vascular system. (google.es)
- 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)
- Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. (fishersci.com)
- The encoded protein disrupts the vascular remodeling ability of ANGPT1 and may induce endothelial cell apoptosis. (antibodies-online.com)
- 1,2 Recruitment of mural cells, which differentiate to vascular smooth muscle cells (VSMCs) and pericytes, to the endothelial tube is required for stabilization of the vessels. (ahajournals.org)
- it disrupts ANGPT1's vascular remodelling activity and may induce endothelial cell apoptosis. (thefreedictionary.com)
- This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. (origene.com)
- Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. (origene.com)
- Objective- Calcineurin (Cn) and the nuclear factor of activated T cells (NFAT) family of transcription factors are critical in vascular smooth muscle cell (SMC) development and pathology. (ahajournals.org)
- Conclusion- We hereby report PROCR as a novel, NFAT-dependent gene that may be implicated in vascular restenosis and consequent inward remodeling. (ahajournals.org)
- Several NFAT target genes, although limited in number, have already been described in vascular SMCs. (ahajournals.org)
VEGFR2
- The biological functions of VEGF are mediated by its binding to one of the VEGF receptor tyrosine kinases, which include VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). (hindawi.com)
- This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms which bind and activate VEGFR-2 and VEGFR-3 receptors. (antibodies-online.com)
Surface receptor10
- It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and medi. (genecards.org)
- It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. (genecards.org)
- The targeted App gene encodes amyloid beta precursor protein, a transmembrane cell surface receptor that is cleaved by secretases. (jax.org)
- c-Src is a widely studied member of non-receptor tyrosine kinases which are not associated with a cell-surface receptor. (wikipedia.org)
- Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1) pipeline Target constitutes close to 23 molecules. (reportsweb.com)
- It plays an essential role as cell surface receptor for neuregulins. (reportsweb.com)
- It also reviews key players involved in Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC 2.7.10.1) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsweb.com)
- Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. (nih.gov)
- The protein encoded by the c-MET gene is a cell surface receptor known as the mesenchymal epithelial transition factor, or MET receptor. (onclive.com)
- The protein encoded by this gene is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor and a member of the GDNF receptor family. (wikipedia.org)
ErbB3
- Flowcytometric analysis performed using various cancer cell lines revealed that this Monoclonal antibody exhibited high binding affinity with BT474 and SKBR3 cells whichoverexpresses C-erbB-2. (iospress.com)
- LRIG1 was found to interact with ErbB receptors and downregulate their function. (diva-portal.org)
- Several growth factors, including EGF, transforming growth factor-α (TGF-α), amphiregulin (AR), epiregulin (EREG), heparin-binding EGF (HB-EGF), betacellulin (BTC), and epigen (EPG) bind to the ErbB receptors. (aacc.org)
Soluble1
- From the data obtained from SAXS experiments it can be concluded that the protein (soluble IRR ectodomain) in solution exists as a dimer having a molecular mass close to that calculated from an amino acid sequence with the contribution of glycosylation, but we can't find significant differences in X-ray scattering between conditions of pH 7.0 and pH 9.0. (ibch.ru)
Antibodies4
- Search, Find and Buy Antibodies, ELISA Kits and Proteins. (antibodies-online.com)
- Dopaminergic neurons of the mouse can be visualized by immunohistochemistry using antibodies against tyrosine hydroxylase (TH). (plymouth.ac.uk)
- Recent successful development of targeted intervention agents has been based on the use of small molecules and antibodies directed to disregulated tyrosine kinases ( 2 , 3 ). (pnas.org)
- Custom ELISA Kits, Recombinant Proteins and Antibodies can be designed, manufactured and produced according to the researcher's specifications. (mybiosource.com)
Variants10
- Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. (wikipedia.org)
- These shRNA constructs were designed against multiple splice variants at this gene locus. (origene.com)
- Multiple transcript variants encoding different isoforms have been found for this gene. (genecards.org)
- Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. (creative-biolabs.com)
- Three transcript variants encoding three different isoforms have been found for this gene. (antibodies-online.com)
- Two transcript variants encoding the same protein have been found for this gene. (wikipedia.org)
- Alternate transcriptional splice variants encoding different isoforms have been characterized. (ucsc.edu)
- Multiple alternatively spliced variants, encoding the same protein, have been identified. (nih.gov)
- Alternative splicing of this gene results in multiple transcript variants. (abnova.com)
- Alternative splicing results in multiple transcript variants encoding different isoforms. (merckmillipore.com)
Affinity7
- All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. (wikipedia.org)
- The low affinity receptor (Kd approximately 10(-9) to 10(-8) M) is a cysteine-rich glycoprotein encoded by the previously characterized LNGFR gene. (nih.gov)
- The structural nature of the high affinity receptor (Kd approximately 10(-11) to 10(-10) M) has yet to be established. (nih.gov)
- High affinity binding of NGF to gp140trk can occur in the absence of low affinity LNGFR receptors, at least in nonneural cells. (nih.gov)
- However, for a precise elucidation of the role of the N-Ras(A18T) mutant in melanoma, additional studies aimed to measure the affinity to guanine nucleotide exchange factors and GTPase-activating proteins are needed. (aacrjournals.org)
- Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. (merckmillipore.com)
- The higher affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. (rupress.org)
Type III receptor tyrosi1
- This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. (fishersci.com)
Amplification4
- One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. (nih.gov)
- Previous studies have identified a number of molecular alterations in glioblastoma, including amplification of the RTK epidermal growth factor receptor. (pnas.org)
- Labeled FISH probes for identification of gene amplification using Fluoresecent In Situ Hybridization Technique. (abnova.com)
- Human lung squamous cell carcinoma showed no VEGFR2 gene amplification. (abnova.com)
Growth factor r3
- Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. (springer.com)
- In most photoreceptor precursors, Ras1/MAPK is activated by the RTK Drosophila Epidermal Growth Factor Receptor (DER) ( Freeman, 1996 ). (biologists.org)
- Because the only difference between the corrupt and well-mannered cells was the amount of HER2, these results indicated that surplus growth factor receptor unbridles normal restraints on replication. (laskerfoundation.org)
Assays2
- DiscoveRx offers cell-based assays that target other members of this gene family or functional group. (discoverx.com)
- A shift toward the use of more whole-cell-based RTK assays is expected to lead to a better prediction of the clinical outcome of new drug candidates. (aspetjournals.org)
Family of protein tyrosin2
- Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non receptor tyrosine kinases which do not possess transmembrane domains. (wikipedia.org)
- This gene is a member of the Src family of protein tyrosine kinases (PTKs). (nih.gov)
Grb22
- Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development. (springer.com)
- When phosphorylated, interacts directly with the PIK3R1 subunit of phosphoinositide 3-kinase and the SH2 domains of GRB2, GRAP, GRAP2, PLCG1 and PLCG2. (merckmillipore.com)
Anaplastic lympho2
- 4 , 5 The genes altered in the t(2;5) translocation contain the N-terminal portion of nucleophosmin ( NPM ) gene, a nuclear phosphoprotein, fused to the catalytic domain of anaplastic lymphoma kinase ( ALK ) gene. (bloodjournal.org)
- Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. (nih.gov)
Adaptor1
- TYROBP (Transmembrane Immune Signaling Adaptor TYROBP) is a Protein Coding gene. (genecards.org)
Targets5
- In addition to nuclear targets, some MAP kinase substrates are located in the cytoplasm, e.g. , the guanine nucleotide exchange factor SOS and the protein kinase pp90Rsk (reviewed in F errell 1996 ). (genetics.org)
- It is now clear that tyrosine kinases represent attractive targets for therapeutic intervention in cancer. (pnas.org)
- Therefore, further determining genomic alterations within this gene family and assessing their biological role might provide targets to expand therapeutic interventions for cancer. (pnas.org)
- To find molecular targets, we have sequenced the coding exons for the kinase domains of 20 human receptor tyrosine kinase (RTK) genes in glioblastomas. (pnas.org)
- Here, we used a genomics approach to identify and validate NFAT gene targets activated during platelet-derived growth factor-BB (PDGF-BB)-induced SMC phenotypic modulation. (ahajournals.org)
Signaling17
- Ieraci A, Forni PE, Ponzetto C. Viable hypomorphic signaling mutant of the Met receptor reveals a role for hepatocyte growth factor in postnatal cerebellar development. (springer.com)
- Also able to mediate GDNF signaling through the RET tyrosine kinase receptor. (genecards.org)
- The viral glycoprotein gp55, from the spleen focus forming virus, interacts with the erythropoietin receptor (EpoR) ( 18 ) and Sf-Stk ( 23 ), and this signaling complex drives the Epo-independent expansion of Friend virus-infected cells. (asm.org)
- In this report, we link Notch signaling to platelet-derived growth factor (PDGF) signaling, a key determinant of VSMC biology, and show that PDGF receptor ( PDGFR )-β is a novel immediate Notch target gene. (ahajournals.org)
- Notch signaling is important for development of both endothelial and mural cells. (ahajournals.org)
- Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling. (nih.gov)
- The clinical course of chronic lymphocytic leukemia (CLL) differs significantly between patients with mutated (M-CLL) and unmutated (U-CLL) immunoglobulin (Ig) variable heavy-chain (V H ) genes, implying a role for B-cell receptor (BCR) signaling in the pathogenesis of this disease. (bloodjournal.org)
- These data demonstrate that only sustained BCR signaling can promote survival of CLL B cells and indicate that the main difference between CLL with mutated and unmutated V H genes may reside in the availability of such stimulation. (bloodjournal.org)
- Using one such system, the AND mouse, whose CD4+ V3-TCR+ (Trg+) identify amino acids 88 to 103 of the pigeon cytochrome C (PCC) protein, we have demonstrated in vitro age-related problems in immunosynapse (Garcia & Miller 2001), exclusion of CD43 from the site of synapse formation (Garcia & Miller 2003), TCR signaling (Miller 2005), and the appearance of CD69 and CD25 guns (Garcia & Miller 2003). (exposed-skin-care.net)
- Ras, a small GTP-binding protein, is required for functional receptor tyrosine kinase signaling. (asm.org)
- Synapse development and plasticity: roles of ephrin/Eph receptor signaling. (springer.com)
- Signaling by glutamate is mediated by a large and diverse number of receptors that include ionotropic receptors that mediate rapid excitatory neurotransmission. (jneurosci.org)
- LRIG1 was found to restrict growth factor signaling by enhancing receptor ubiquitylation and degradation. (diva-portal.org)
- Genetic ablation of the Lyn tyrosine kinase has revealed unique inhibitory roles in B lymphocyte signaling. (rupress.org)
- These studies highlight the difficulty in maintaining tolerance in the face of chronic stimulation and emphasize the pivotal role of Lyn in B cell signaling. (rupress.org)
- Cytoplasmic protein tyrosine phosphatases such as SHP-1 also modulate BCR signaling ( 9 ) as exemplified by the severe B cell lymphopenia and autoantibody production of motheaten mice ( 10 ) that carry a debilitating mutation in SHP-1 ( 11 , 12 ). (rupress.org)
- The dual nature of Lyn's role in the regulation of B cell signaling makes it a potentially critical target in analyzing the development of B cell dysfunction. (rupress.org)
Neurotrophic2
- This gene encodes a cell surface glycoprotein and member of the glial cell line-derived neurotrophic receptor (GDNFR) family of proteins. (jax.org)
- These findings indicate that gp145trkB may function as a neurotrophic receptor for BDNF and NT-3. (nih.gov)
Overexpression4
- The clinicopathological features associated with overexpression of the MET gene were also correlated. (aacrjournals.org)
- Moreover, the overexpression of MET protein was more often seen in well/moderately differentiated than in poorly differentiated ESCC. (aacrjournals.org)
- Infection with Epstein-Barr virus results in the overexpression of this gene. (nih.gov)
- Overexpression vector and transfection into 293H cell line. (abnova.com)
Molecules9
- Thus the eph protein may define a new class of these molecules. (sciencemag.org)
- Immunoregulatory molecules, including T cell hybridomas, will also be featured. (iospress.com)
- Several different treatment strategies such as drug intervention (steroidal/nonsteroidal), growth factors, cellular metabolites (cAMP/GTPases), small molecules, extracellular matrices, and cellular therapy involving pluripotent stem cells/mesenchymal stem cells (MSCs)/neural progenitor cells (NPCs/NSCs) are being tested for successful therapeutic intervention [ 9 ]. (hindawi.com)
- Macrophage Stimulating Protein Receptor (CDw136 or Protein Tyrosine Kinase 8 or p185 Ron or CD136 or MST1R or EC 2.7.10.1) pipeline Target constitutes close to 7 molecules. (express-press-release.net)
- STAP1 has direct interactions with proteins and molecules. (creativebiomart.net)
- We selected proteins and molecules interacted with STAP1 here. (creativebiomart.net)
- Tyrosine Protein Kinase Mer (Proto Oncogene c Mer or Receptor Tyrosine Kinase MerTK or MERTK or EC 2.7.10.1) pipeline Target constitutes close to 17 molecules. (reportsnreports.com)
- This approach-in which a therapy would fixate on molecules that dwell specifically in cancer cells and also drive malignancy-held great appeal. (laskerfoundation.org)
- Lyn up/up mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, and elevated numbers of B1a B cells. (rupress.org)
Epidermal growth4
- The lin-3 gene encodes a protein similar to epidermal growth factor (EGF) that is the inductive signal secreted by the anchor cell ( H ill and S ternberg 1992 ). (genetics.org)
- This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. (creative-biolabs.com)
- The encoded protein is synthesized as a large precursor molecule that is proteolytically cleaved to generate the 53-amino acid epidermal growth factor peptide. (antibodies-online.com)
- This protein is a receptor for members of the epidermal growth factor family. (discoverx.com)
Interact6
- Angiopoietin 1 has been shown to interact with TEK tyrosine kinase. (wikipedia.org)
- When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the flexible linker domain and thereby keeps the inactive unit tightly bound. (wikipedia.org)
- Under normal conditions Muc4 and ErbB2 are separated by adherens and tight junctions, however in signet ring cells they are able to interact, since these junctions have been lost. (cancerindex.org)
- There are some 23,000 genes within the human genome that carry the instructions for making a wide spectrum of proteins, many of which interact with each other in an interwoven mesh of complicated networks. (xconomy.com)
- Conversely, interneurons of the locomotory control circuit (AVA, AVB, AVD, AVE, and PVC) coexpressed up to six subunits, suggesting that these subunits interact to generate a diversity of heteromeric glutamate receptor channels that regulate various aspects of worm movement. (jneurosci.org)
- Broadly, his research addresses fundamental questions, such as how proteins and nucleic acids interact to store and release energy, to transduce signals, and to perform tasks of chemistry underlying reproduction. (herpesvirusworkshop.com)
Human genome2
- Of the 90 unique tyrosine kinase genes identified in the human genome, 59 encode receptor tyrosine kinase proteins. (wikipedia.org)
- A catalog of 518 human protein kinases has been discerned from the human genome sequence ( 1 ). (pnas.org)
VEGFR24
- The antiserum was produced against a chemically synthesized phosphopeptide derived from the region of human VEGFR2 that contains tyrosines 1054 and 1059. (thermofisher.com)
- Recognizes endogenous levels of VEGFR2 (pY1175) protein. (genetex.com)
- Immunofluorescent analysis of VEGFR2 (pY1175) staining in MCF7 cells. (genetex.com)
- Human lung squamous cell carcinoma (FFPE) stained with VEGFR2/CEN4p FISH Probe. (abnova.com)
Endothelial cells6
- 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)
- Kanda, " Angiopoietin 2 stimulates migration and tube-like structure formation of murine brain capillary endothelial cells through c-Fes and c-Fyn," Journal of Cell Science, vol. (thefreedictionary.com)
- Endothelial cells express the MET gene and expose at the cell surface the mature protein (p190MET) made of a 50 kD (alpha) subunit disulfide linked to a 145-kD (beta) subunit. (rupress.org)
- HGF binding to endothelial cells identifies two sites with different affinities. (rupress.org)
- HGF stimulates the scatter of endothelial cells grown on three-dimensional collagen gels, inducing an elongated phenotype. (rupress.org)
- HGF lacks activities related to hemostasis-thrombosis, inflammation and endothelial cells accessory functions. (rupress.org)