Focal Adhesions: An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.Paxillin: Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.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.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.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Zyxin: A zinc-binding phosphoprotein that concentrates at focal adhesions and along the actin cytoskeleton. Zyxin has an N-terminal proline-rich domain and three LIM domains in its C-terminal half.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Cell Adhesion: Adherence of cells to surfaces or to other cells.Vinculin: A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10.Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.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.PhosphoproteinsCrk-Associated Substrate Protein: Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Focal Adhesion 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.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.LIM Domain Proteins: A large class of structurally-related proteins that contain one or more LIM zinc finger domains. Many of the proteins in this class are involved in intracellular signaling processes and mediate their effects via LIM domain protein-protein interactions. The name LIM is derived from the first three proteins in which the motif was found: LIN-11, Isl1 and Mec-3.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Talin: A 235-kDa cytoplasmic protein that is also found in platelets. It has been localized to regions of cell-substrate adhesion. It binds to INTEGRINS; VINCULIN; and ACTINS and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton.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.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.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.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.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 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.Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.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.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Protein-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.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.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.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.Retinoblastoma-Like Protein p130: A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. RBL2 contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and E2F5 TRANSCRIPTION FACTOR. RBL2 also interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.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 enzymesIntegrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.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.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.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.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.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.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.Microfilament Proteins: Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.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.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.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 Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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.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.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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)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.Cell Line, Tumor: A cell line derived from cultured tumor cells.Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.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.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.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.Tyrphostins: A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.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).Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.Kinetics: The rate dynamics in chemical or physical systems.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.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.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.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.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.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.ZAP-70 Protein-Tyrosine Kinase: A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.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.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.Transduction, Genetic: The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.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.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.Lactams, Macrocyclic: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.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.Intercellular Adhesion Molecule-1: A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.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.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.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.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.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.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).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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Protein Sorting Signals: Amino acid sequences found in transported proteins that selectively guide the distribution of the proteins to specific cellular compartments.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.Tissue Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.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.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Antigens, CD29: Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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).)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Cadherins: Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Genes, src: Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.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, 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.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Mice, Inbred C57BLProto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.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.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.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.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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)Vascular Cell Adhesion Molecule-1: Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154)Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.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).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.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Janus Kinase 1: A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.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.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.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.rhoA GTP-Binding Protein: A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.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.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.NIH 3T3 Cells: A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)Stress Fibers: Bundles of actin filaments (ACTIN CYTOSKELETON) and myosin-II that span across the cell attaching to the cell membrane at FOCAL ADHESIONS and to the network of INTERMEDIATE FILAMENTS that surrounds the nucleus.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.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.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.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.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.PiperazinesElectrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Bacterial Adhesion: Physicochemical property of fimbriated (FIMBRIAE, BACTERIAL) and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity.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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.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.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Benzamides: BENZOIC ACID amides.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.GTPase-Activating Proteins: Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)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.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.
... on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction ... this domain is also found in the focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine ... Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the ... Mice that do not express TYK2 have defective natural killer cell function. Since members of the type I and type II cytokine ...
"Distinct domains of the protein tyrosine kinase tyk2 required for binding of interferon-alpha/beta and for signal transduction ... Tonks NK, Neel BG (November 1996). "From form to function: signaling by protein tyrosine phosphatases". Cell. 87 (3): 365-8. ... an integrin-binding domain and a focal adhesion-binding domain (Fak family). The nRTK Abl possess the SH2 and SH3 domains, but ... mutations in the SH3 domain result in activation of Abl and cellular transformation. ZAP70/Syk and JAKs The kinase activity of ...
"Insulin receptor substrate-1 as a signaling molecule for focal adhesion kinase pp125(FAK) and pp60(src)". The Journal of ... IRS-1 signal transduction may be inhibited by SHP2 in some tissues. Tyrosine phosphorylation of the insulin receptors or IGF-1 ... The cellular protein levels of IRS-1 are regulated by the Cullin7 E3 ubiquitin ligase, which targets IRS-1 for ubiquitin ... Ablation of IRS-1 alters downstream signalling through phosphatidylinositol-3 kinase (PI3K), causing an increased interaction ...
... expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction ... Schlaepfer DD, Hauck CR, Sieg DJ (1999). "Signaling through focal adhesion kinase". Progress in Biophysics and Molecular ... Saleem A, Datta R, Yuan ZM, Kharbanda S, Kufe D (Dec 1995). "Involvement of stress-activated protein kinase in the cellular ... "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". Journal of Leukocyte Biology. ...
... also contributes to the transduction of signals downstream receptor tyrosine kinases (RTKs). A role for NEDD9 in ... Focal adhesion targeting (FAT) domain The FAT-like C-terminal domain is highly conserved in focal adhesion proteins, and ... NEDD9 is a noncatalytic scaffolding protein that contains docking sites for proteins involved in multiple signal transduction ... "NEDD9 stabilizes focal adhesions, increases binding to the extra-cellular matrix and differentially effects 2D versus 3D cell ...
Many Ser/Thr and dual-specificity protein kinases are important for signal transduction, either acting downstream of [receptor ... Such signaling is mainly orchestrated in focal adhesions, regions where the integrin-bound actin cytoskeleton detects changes ... the analysis of signaling pathways and networks has become an essential tool to understand cellular functions and disease, ... Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain ...
... in the cytoplasm and is an adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal ... Goicoechea SM, Tu Y, Hua Y, Chen K, Shen TL, Guan JL, Wu C (July 2002). "Nck-2 interacts with focal adhesion kinase and ... "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. 65 (4): 523-34 ... "Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)". ...
"The p38 signal transduction pathway: activation and function". Cellular Signalling. 12 (1): 1-13. doi:10.1016/s0898-6568(99) ... "PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ... "Doxazosin induces activation of GADD153 and cleavage of focal adhesion kinase in cardiomyocytes en route to apoptosis". ... p38α MAPK is mainly activated through MAPK kinase kinase cascades and exerts its biological function via downstream substrate ...
"Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation". Nature ... "Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic ... The N-terminal helix contains a phosphorylatable tyrosine (Y925) implicated in signal transduction. Two hydrophobic patches ... thereby preventing the signalling function of FAK. Release of this auto-inhibitory interaction has been shown to occur within ...
This family also includes Abl, Src, focal adhesion kinase and Janus kinase.) Fyn is located downstream of several cell surface ... Fyn is a protein, present in the signaling pathway of integrins, which activates ras. Fyn is a tyrosine-specific phospho- ... "Regulation of Src Family Kinases in Human Cancers". Journal of Signal Transduction. 2011: 1-14. doi:10.1155/2011/865819. ISSN ... Fyn's normal function in cellular growth and proliferation has the potential to be exploited in the progression and metastasis ...
"Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase". Nature Cell Biology. 7 (6): ... Microtubules can act as substrates for motor proteins that are involved in important cellular functions such as vesicle ... However, the signal transduction mechanisms involved in this communication are little understood. Notwithstanding this, the ... Signals sent between the follicular cells and the oocyte (such as factors similar to epidermal growth factor) cause the ...
... such as cellular localization and cellular migration. Endoglin can also mediate F-actin dynamics, focal adhesions, microtubular ... Also, the downstream TGF-beta/bone morphogenic protein (BMP) signaling pathway, which includes Smad1 and Smad2/3, were ... Luft FC (Nov 2006). "Soluble endoglin (sEng) joins the soluble fms-like tyrosine kinase (sFlt) receptor as a pre-eclampsia ... Feb 2016 Attisano L, Wrana JL (Dec 1996). "Signal transduction by members of the transforming growth factor-beta superfamily". ...
... -1 and tyrosine kinase signaling are essential for regulating blood vessel development and the stability of mature ... Tie-1 heterodimerizes with Tie-2 to enhance and modulate signal transduction of Tie-2 for vascular development and maturation. ... This growth factor is also a glycoprotein and functions as an agonist for the tyrosine receptor found in endothelial cells. ... This in turn initiates the binding and activation of downstream intracellular enzymes, a process known as cell signaling. Tie-2 ...
protein kinase activity. • protein serine/threonine kinase activity. Cellular component. • membrane. • focal adhesion. • ... Molecular function. • signal transducer, downstream of receptor, with protein tyrosine phosphatase activity. • protein N- ... and intracellular signals. As an essential component of the MAP kinase signal transduction pathway, this kinase is involved in ... protein binding. • protein serine/threonine/tyrosine kinase activity. • protein tyrosine kinase activity. • nucleotide binding ...
protein tyrosine kinase activity. • ATP binding. • collagen binding. Cellular component. • integral component of membrane. • ... focal adhesion. • integral component of plasma membrane. • extracellular exosome. • apical plasma membrane. • plasma membrane. ... which are involved in pleiotropic effects of signal transduction. DDR2 has been associated with a number of diseases including ... Molecular function. • transferase activity. • nucleotide binding. • protein kinase activity. • kinase activity. • protein ...
"Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src ... The CRK protein participates in the Reelin signaling cascade downstream of DAB1. Adapter molecule crk is a member of an adapter ... "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction ... protein with the SH2 and SH3 domains of cellular Crk. The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian ...
scaffold protein binding. Cellular component. • cytoplasm. • cytosol. • membrane. • kinesin complex. • focal adhesion. • ... Function[edit]. This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to ... "Protein binding and signaling properties of RIN1 suggest a unique effector function". Proc. Natl. Acad. Sci. U.S.A. 94 (10): ... "Hepatitis C Virus Core Protein Interacts with 14-3-3 Protein and Activates the Kinase Raf-1". J. Virol. 74 (4): 1736-41. doi: ...
"Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase ... "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions". Nature. 376 (6543 ... between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that ... Ueda H, Abbi S, Zheng C, Guan JL (April 2000). "Suppression of Pyk2 kinase and cellular activities by FIP200". J. Cell Biol. ...
"Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through ... "Functions of the adapter protein Cas: signal convergence and the determination of cellular responses". Oncogene. 20 (44): 6448- ... RTK-dependent p130Cas/BCAR1 tyrosine phosphorylation and the subsequent binding with specific downstream signaling molecule ... Rozengurt E (1999). "Signal transduction pathways in the mitogenic response to G protein-coupled neuropeptide receptor agonists ...
... is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling ... "Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine ... Goldmann WH (2003). "p56(lck) Controls phosphorylation of filamin (ABP-280) and regulates focal adhesion kinase (pp125(FAK))". ... which is involved in further downstream signaling activation. The tyrosine phosphorylation cascade initiated by Lck and Fyn ...
"Protein tyrosine kinase activation provides an early and obligatory signal in anti-FRP-1/CD98/4F2 monoclonal antibody induced ... the function of SFRP1 in different tissues because an untethered protein may be more effective in antagonizing Wnt signaling to ... The directed movements of EC during de novo vessel formation are coordinated through cellular adhesion mechanisms, cytoskeletal ... Since heparin is highly negatively charged and cannot permeate the membrane, it must activate a signal transduction pathway to ...
Protein Phosphatase type 1 (PP1), sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2), and focal adhesion kinase (FAK). The ... Therefore, cMLCK is a downstream protein regulated by NRG-1/ErbB signaling and plays a role in rhNRG-1-mediated improvements in ... The role of erbB2 signal transduction pathways in human breast cancer". Breast Cancer Res. Treat. 27 (1-2): 83-93. doi:10.1007/ ... and enhancing pumping function. Downstream effectors of NRG-1/ErbB, include cardiac-specific myosin light chain kinase (cMLCK ...
Signal transduction pathways regulated via RhoA link plasma membrane receptors to focal adhesion formation and the subsequent ... "Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling". J. Biol. ... functioning as targets for RhoA while simultaneously maintaining the integrity of normal cellular processes and normal breast ... Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003). "RhoE binds to ROCK I and inhibits downstream signaling". Mol. Cell ...
"Multiple pathway signal transduction by the cAMP-dependent protein kinase". FASEB J. 8 (15): 1227-36. doi:10.1096/fasebj.8.15. ... Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... function of cAMP-dependent protein kinase. In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein ... The pathway may also be deactivated downstream by directly inhibiting adenylyl cyclase or dephosphorylating the proteins ...
Ribosomal s6 kinase *RPS6KA1. Tyrosine:. *ZAP70. *Focal adhesion protein-tyrosine kinase *PTK2 ... Function[edit]. G proteins are important signal transducing molecules in cells. "Malfunction of GPCR [G Protein-Coupled ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ... "G-proteins and the role of these proteins in signal transduction in cells". 10 October 1994 ...
identical protein binding. Cellular component. • cytoplasm. • cytosol. • membrane. • focal adhesion. • extrinsic component of ... signal transduction. • positive regulation of Rac protein signal transduction. • positive regulation of gene expression. • ... regulation of protein stability. • epidermal growth factor receptor signaling pathway. • positive regulation of MAP kinase ... and modulates its downstream signaling". Molecular and Cellular Biology. 21 (21): 7345-54. doi:10.1128/MCB.21.21.7345-7354.2001 ...
... inhibition of protein tyrosine phosphatases by oxidation, and increased tyrosine kinase signaling. In cells dependent on ... Tyrosine phosphorylation plays a critical role in regulating cellular function and is a central feature in signaling cascades ... that glucose withdrawal initiates a unique signature of phospho-tyrosine activation that is associated with focal adhesions. ... and the importance of understanding not only the effects of oncogenic signal transduction on metabolism, but also the impact of ...
Growth factor receptor-bound protein 2), Authors: Gagani Athauda, Donald P Bottaro. Published in: Atlas Genet Cytogenet Oncol ... as well as non-receptor tyrosine kinases (TKs) such as BCR-Abl and focal adhesion kinase (FAK), intracellular effectors such as ... EGF Signaling Pathway [Genes] EPO Signaling Pathway [Genes] Role of ERBB2 in Signal Transduction and Oncology [Genes] ... Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient ...
On the cellular level, Neurotensin can lead to tyrosine phosphorylation of the focal adhesion kinase, a protein that localizes ... SHPS-1 and CD47 are a cell-cell communication and signal transduction system with multiple functions in immune cells (Han et al ... a, Green signals indicate Pleiotrophin; red signals indicate PSA-NCAM. e, Green signals indicate GFAP; red signals indicate ... Differentially expressed downstream components of the inositol phospholipid pathway were also found: Pten-induced kinase, PLC δ ...
Focal adhesion kinase (fak) is a tyrosine kinase located predominantly in focal adhesions, ie, the cellular sites of attachment ... Upstream and downstream effectors of this signal transduction pathway are not affected by GA (Schulte et al 1996). Further ... Destabilization of raf-1 by geldanamycin leads to disruption of the raf-1-MEK-mitogen-activated protein kinase signaling ... assumed inhibition of tyrosine kinases, and (3) binding to and interference with the function of members of the Hsp90 family of ...
These novel functions of MFG-E8 are primarily mediated through its receptor αvβ3-integrin. Here we focus on the pivotal role of ... We propose further investigation of the molecular pathways for MFG-E8 signaling in NSPC and effective strategies for MFG-E8 ... These novel functions of MFG-E8 are primarily mediated through its receptor αvβ3-integrin. Here we focus on the pivotal role of ... We propose further investigation of the molecular pathways for MFG-E8 signaling in NSPC and effective strategies for MFG-E8 ...
Signaling by PTK6, organism-specific biosystemPTK6 (BRK) is an oncogenic non-receptor tyrosine kinase that functions downstream ... Signaling events mediated by focal adhesion kinase, organism-specific biosystem. Signaling events mediated by focal adhesion ... Downstream signal transduction, organism-specific biosystem (from REACTOME) Downstream signal transduction, organism-specific ... cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, ...
... tyrosine kinase.. Ras proteins function as molecular switches that facilitate transduction of extracellular signals. Ras ... FAK, focal adhesion kinase; GRB2, growth factor receptor-binding protein 2; IMP, impedes mitogenic signal propagation; IRS-1, ... These effects seem to be mediated by tyrosine kinase receptors and their downstream signaling effectors through regulated ... Ras family proteins regulate important GFR-induced signaling pathways contributing to cellular differentiation and ...
... on the JAK family of tyrosine kinases to phosphorylate and activate downstream proteins involved in their signal transduction ... this domain is also found in the focal adhesion kinase (FAK) family and is involved in association of JAKs with cytokine ... Janus kinase (JAK) is a family of intracellular, nonreceptor tyrosine kinases that transduce cytokine-mediated signals via the ... Mice that do not express TYK2 have defective natural killer cell function. Since members of the type I and type II cytokine ...
Regulation of signal transduction through protein cysteine oxidation. Antioxid Redox Signal. 2006; 8: 1819-1827. ... where they remove phosphates from downstream substrates thereby counterbalancing effects of protein tyrosine kinases (PTK). ... SHP-2 dephosphorylated focal adhesion-associated proteins including paxillin, p130Cas, and tensin with associated decreased ... AKT regulates cellular functions such as migration, proliferation, differentiation, and apoptosis and is critically involved in ...
... analysis indicated a role of Agrin in maintaining focal adhesion integrity through stimulation of focal adhesion kinase (FAK). ... More importantly, Lrp4-MuSK as well as integrin-FAK pathways are crucial downstream signaling axes of Agrins functions in ... The signal transduction network initiated by Agrin activates the oncogenic program in liver by negatively regulating tumor ... Despite offering poor survival advantage, broad spectrum receptor tyrosine kinase inhibitors are the sole chemotherapeutic ...
Protein Coding), FGR Proto-Oncogene, Src Family Tyrosine Kinase, including: function, proteins, disorders, pathways, orthologs ... and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction ... Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, ... Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on ...
Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature 376:737-745. ... Angiotensin II signal transduction in vascular smooth muscle: pathways activated by specific tyrosine kinases. J. Am. Soc. ... coordinating downstream signaling events (13, 40, 42). We therefore hypothesized that Pyk2 is involved in PDK1 phosphorylation ... focal adhesion kinase, and the serine/threonine kinase p21-activated kinase (PAK), as well as the scaffolding proteins paxillin ...
... cells and function in the coordination of [[tyrosine kinase]] mediated [[signal transduction]]. ==Domains== The [[SH2 domain]] ... Signaling through focal adhesion kinase. ,journal=Prog. Biophys. Mol. Biol. ,volume=71 ,issue= 3-4 ,pages= 435-78 ,year= 1999 , ... tyrosine kinase]] to the activation of [[Ras]] and its downstream kinases, [[Mitogen-activated protein kinase,ERK1,2]]. Grb2 is ... Function and expression== Grb2 is widely expressed and is essential for multiple [[Cell (biology),cellular]] functions. ...
... tyrosine kinase that plays critical roles in integrin-mediated signal transductions and also participates in signaling by other ... multiple downstream signaling pathways through phosphorylation of other proteins to regulate different cellular functions. ... In integrin-mediated cell adhesion, FAK is activated via disruption of an auto-inhibitory intra-molecular interaction between ... Those signaling pathways are identified to mediate FAK regulation of migration of various normal and cancer cells. Serine 910 ( ...
Cellular characterization of a novel focal adhesion kinase inhibitor. J. Biol. Chem. 282:14845-14852. doi:10.1074/jbc. ... EGF binds to the EGF receptor to initiate signal transduction through multiple downstream signal mediators. For neurons, it has ... Signalling pathways regulating nucleo-cytoplasmic shuttling of the mRNA-binding protein HuR. Cell. Signal. 20:2165-2173. doi: ... Role of Src family tyrosine kinases in the down-regulation of epidermal growth factor signaling in PC12 cells. Genes Cells. 10: ...
Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein ... Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nat Cell Biol. ... Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar ... Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic ...
Ab42578 is an active protein fragment produced in Escherichia coli and has been validated in Phosphatase Activity. Abcam ... Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the ... Deoxycholic acid differentially regulates focal adhesion kinase phosphorylation: role of tyrosine phosphatase ShP2.. Am J ... Cellular and biochemical assays. By product type. Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists ...
... a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and ... activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation ... Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of ... a regulator for Rho family GTPases implicated in various neural functions, and SNCA, ...
EGFR receives signal from focal adhesion kinase (FAK), mediating cell migration (82). ... IGF1R is a tyrosine kinase that activates PI3K/Akt and RAS-RAF-MAPK signaling pathways (78). In glioblastoma, the stimulation ... MSI1 functions as a downstream effector of TNC in metastases (76, 77). Therefore, an interesting feedback loop involving MSI1 ... thus allowing for cellular adhesion as well as signal transduction. Alterations of integrin expression, particularly ...
Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. ... Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration. J ... Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration ... Categories: Human , Large Structures , Receptor protein-tyrosine kinase , Ivancic, M , Lyons, B A , Hormone-growth factor- ...
... and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. ... Focal adhesion, organism-specific biosystem (from KEGG) Focal adhesion, organism-specific biosystemCell-matrix adhesions play ... Signal Transduction, organism-specific biosystem (from REACTOME) Signal Transduction, organism-specific biosystem ... Kit Receptor Signaling Pathway, organism-specific biosystemKit is a receptor protein tyrosine kinase, which is a receptor for ...
1992) pp125FAK, a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA 89: ... is a downstream event in rho-regulated signal transduction ((25)) which precedes cell spreading or tyrosine phosphorylation of ... strongly suggest that invasion of epithelial cells by Shigella involves cellular functions associated with focal adhesion ... tyrosine phosphorylation of focal adhesion proteins such as FAK and paxillin, and transmission of extracellular signals into ...
YopH tyrosine dephosphorylates host cell proteins, such as p130Cas and focal adhesion kinase FAK (2). By action of these Yops, ... III protein secretion machinery to deliver bacterial effector proteins into the host cell for modulation of cellular functions ... LPS-initiated signal transduction strongly enhances the apoptosis-inducing capacity of YopP, indicating that LPS actively ... Studies presently underway address implications of proximal LPS-signaling intermediates in the regulation of apoptotic signal ...
... protein tyrosine phosphatases (PTPs), and protein tyrosine kinases via reversible oxidation of thiol groups of low pKa cysteine ... focal adhesions, and mitochondria [62]. NOX4 requires the cofactor for production of ROS, of which predominantly H2O2 is ... However, given its essential role in a wide range of fundamental cellular functions, there are concerns that systemic ... indirect interactions are required for signal transduction of some growth factors; for example, integrin binding is necessary ...
Both proteins play a role in activation of mammary stem ce... ... GH and Wnt signaling in canine mammary cancer, how the family ... Both proteins play a role in activation of mammary stem cells. In this review we summarize what is known on progesterone, ... of HER-receptors could interact with this signaling, and what this means for comparative and translational oncological aspects ... GHR dimers are transphosphorylated by JAK2 tyrosine kinases that result in activation of multiple downstream signaling pathways ...
  • 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)
  • Oncogene addiction, that is, the acquired dependence of a cancer cell on the activity of a single oncogenic gene product, has been the basis for the targeted therapy paradigm, and operationally defines such signals. (icr.ac.uk)
  • I will also discuss the challenges in simultaneously harnessing two types of molecular addictions for therapeutic benefit, and the importance of understanding not only the effects of oncogenic signal transduction on metabolism, but also the impact of metabolic states on signal transduction. (icr.ac.uk)
  • The name Grb2 is an abbreviation of Growth factor receptor-bound protein 2. (wikidoc.org)
  • FAT also mediates signaling through Grb2 via phosphorylated Y925. (proteopedia.org)
  • The HGF receptor can associate with several different signaling systems, including src, Grb2/SOS, PI3 kinase and Gab1. (broadinstitute.org)
  • The small adapter protein Grb2, for example, is bound through its SH3 domains to short, proline-rich sequences in the carboxy terminal tail of the guanine nucleotide-releasing factor Sos. (yale.edu)
  • Interaction between Grb2 and Sos with tyrosine phosphorylated RTKs or docking proteins results in translocation of Sos to the plasma membrane allowing the exchange of GDP for GTP on Ras. (yale.edu)
  • A broad range of bacterial pathogens, including the Gram-negative bacterium Yersinia , uses a so-called type III protein secretion machinery to deliver bacterial effector proteins into the host cell for modulation of cellular functions. (jimmunol.org)
  • The type III protein secretion machinery of Yersinia and a set of six effector Yersinia outer proteins (Yops) 3 (YopE, YopH, YopM, YopO/YpkA, YopP/YopJ, YopT) are encoded by a 70-kb virulence plasmid that is common to the three pathogenic Yersinia species ( 1 ). (jimmunol.org)
  • The diverse effector Yops act on different cellular levels to neutralize a multitude of host effector functions ( 1 ). (jimmunol.org)
  • In addition, reduced nicotinamide-adenine dinucleotide phosphate oxidase is known as a Rac effector and p70 S6 kinase (p70S6K) as a Cdc42 effector. (ahajournals.org)
  • The best-characterized effector of Ras is Raf, a MAPK kinase kinase, in the MAPK/ERK cascade. (ahajournals.org)
  • Chlamydia trachomatis , the causative agent of trachoma and sexually transmitted infections, employs a type III secretion (T3S) system to deliver effector proteins into host epithelial cells to establish a replicative vacuole. (prolekare.cz)
  • We identified Ct875, a new Slc1 client protein and T3S effector, which we renamed TepP (Translocated early phosphoprotein). (prolekare.cz)
  • Glycerol monolaurate (GML) is a monoglyceride with potent antimicrobial properties that suppresses T cell receptor (TCR)-induced signaling and T cell effector function. (sciencemag.org)
  • In addition, it is desirable to attempt to relate the antitumor activity of a candidate compound with molecular effects on proteins relevant for the pathogenesis of malignant diseases. (pubmedcentralcanada.ca)
  • Molecular studies revealed the binding of GA to members of the heat shock protein 90 (Hsp90) family of molecular chaperones ( Whitesell et al 1994 ). (pubmedcentralcanada.ca)
  • We propose further investigation of the molecular pathways for MFG-E8 signaling in NSPC and effective strategies for MFG-E8 delivery across the blood-brain barrier, which will help develop MFG-E8 as a future drug candidate for the bedside management of neurodegenerative diseases. (frontiersin.org)
  • In integrin-mediated cell adhesion, FAK is activated via disruption of an auto-inhibitory intra-molecular interaction between its amino terminal FERM domain and the central kinase domain. (miltenyibiotec.com)
  • Elevated NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H 2 O 2 ) supported by concomitant decreases in nitric oxide (NO) signaling and reactive oxygen species scavengers are central factors in the molecular pathogenesis of fibrosis in numerous tissues and organs. (hindawi.com)
  • Thus, a better understanding of the molecular pathways underlying fibrosis and the initiating signals/causes is urgently required for the development of effective therapeutic strategies. (hindawi.com)
  • The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function. (springer.com)
  • Small GTP-binding proteins (G proteins) are monomeric G proteins with a low molecular weight of 20 to 40 kDa. (ahajournals.org)
  • A small G protein acts as a molecular switch that cycles between inactive GDP-bound and active GTP-bound forms. (ahajournals.org)
  • 5-8 Importantly, recent accumulating evidence highlighted the significance of these small G proteins as essential molecular switches that trigger many of the signal transduction and functions of Ang II. (ahajournals.org)
  • When compared to mAbs which are usually large molecular weight proteins of around 150kDa, small molecule cancer drugs are much smaller in size (≤500Da) and thus can translocate through plasma membranes. (oatext.com)
  • In the field of synthetic biology, the study of these behaviors relies on the use of a broad range of molecular tools that enable the real-time manipulation and measurement of key components in the underlying signaling pathways. (sciencemag.org)
  • Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects. (scielo.br)
  • Like any newly discovered protein, the specific molecular targets of PTEN were originally a mystery. (biologists.org)
  • Therefore, Lu/BCAM appears to plays an oncogenic role during tumorigenesis, however, the underlying molecular mechanisms and downstream signaling pathways of Lu/BCAM in tumorigenesis remain elusive. (biomedcentral.com)
  • Nevertheless, the molecular and cellular mechanisms by which FAK promotes mammary tumorigenesis in vivo are not well understood. (aacrjournals.org)
  • Adaptor proteins play a pivotal role in such molecular networks by allowing formation of protein complexes via interactions involving their non-catalytic binding domains. (biomedcentral.com)
  • However, the molecular mechanism of GH-induced cellular insulin resistance is largely unknown. (diabetesjournals.org)
  • With the development of imaging technologies, particularly green fluorescent protein (GFP) and its derivative fluorescent proteins (FPs), it is now convenient to visualize molecular signals at subcellular levels in live cells. (royalsocietypublishing.org)
  • Traditional assays to detect/measure molecular signals usually require the killing of cells, which may cause the alteration of innate information. (royalsocietypublishing.org)
  • With FPs and biosensor-based FPs, molecular signals at different subcellular compartments can be monitored in live cells continuously without damaging the cells. (royalsocietypublishing.org)
  • May also activate the NF-kappa-B signaling cascade. (cusabio.com)
  • These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. (biomedcentral.com)
  • The β and γ subunits of the G‐protein then activate a MAP kinase cascade consisting of Ste7p (a MAP kinase kinase or MEK homolog), Ste11p (a MEK kinase homolog) and the partially redundant MAP kinase homologs Fus3p and Kss1p ( Herskowitz, 1995 ). (embopress.org)
  • Some of the components of this signaling cascade are not only involved in mating but also in inducing morphological transitions of yeast cells. (embopress.org)
  • The protein localizes to plasma membrane ruffles, a. (genecards.org)
  • Nitrogen Cavitation and Differential Centrifugation Allows for Monitoring the Distribution of Peripheral Membrane Proteins in Cultured Cells Mo Zhou 1 , Mark R. Philips 1 1 Langone Medical Center, New York University Here we present protocols for detergent-free homogenization of cultured mammalian cells based on nitrogen cavitation and subsequent separation of cytosolic and membrane-bound proteins by ultracentrifugation. (jove.com)
  • This method is ideal for monitoring the partitioning of peripheral membrane proteins between soluble and membrane fractions. (jove.com)
  • PURPOSE: Advanced glycation endproduct (AGE) formation on the basement membrane of retinal capillaries has been previously described but the impact of these adducts on capillary endothelial cell function vascular repair remains uncertain. (biomedsearch.com)
  • AGE-mediated changes to mRNAs encoding key basement membrane proteins and regulatory enzymes were investigated using real-time RT-PCR. (biomedsearch.com)
  • PH domains, which are found in most of the proteins that interact with the insulin receptor, bind to charged headgroups of specific phosphatidylinositides and are thereby targeted preferentially to membrane structures. (jci.org)
  • The M r 140,000 β-chain spans the membrane and possesses cytoplasmic tyrosine kinase activity and can be detected in its precursor form at M r 170,000. (aacrjournals.org)
  • Lutheran/basal cell adhesion molecule (Lu/BCAM) is a membrane bound glycoprotein. (biomedcentral.com)
  • The anchor symposium on lipid tonss and cell map, which brought together several scientists in the field of biophysics, biochemistry, and cell biological science defined " membrane tonss as little ( 10-200 nanometer ) , heterogenous, extremely dynamic, sterol- and sphingolipid-enriched spheres that compartmentalize cellular procedures. (artspace-jhb.co.za)
  • In contrast to receptor-PTKs (RTKs), cellular PTKs are located in the cytoplasm , the nucleus , or are anchored to the inner leaflet of the plasma membrane . (blogspot.com)
  • Disruption of SCD1 in mouse brown adipose tissue strengthens insulin signaling and results in increased translocation of Glut4 to plasma membrane and enhanced uptake of glucose (4). (cellsignal.com)
  • Differential organization of GSLs with specific membrane proteins and signal transducers in GEMs (GSL-enriched microdomains), initiates signalling events to modify cellular phenotype. (portlandpress.com)
  • Of particular importance is that GSLs can cluster and assemble with membrane proteins and signal transducers to form GEMs (GSL-enriched microdomains), where they are able to initiate signal transduction [ 5 ], and thus profoundly affect the cellular activities associated with tumour cell invasion. (portlandpress.com)
  • The protein is bound to the cell membrane through an anchor, that can be cleaved, causing the secretion of the protein, in a still active form. (prolekare.cz)
  • Those pores are built out of membrane proteins and are called gap junctions. (50webs.com)
  • Part of the Notch protein is released from the cell surface membrane and can act to change the pattern of gene transcription in the cell nucleus. (50webs.com)
  • It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. (mybiosource.com)
  • Slg1p and Mid2p are both plasma membrane proteins with partial overlapping functions. (sdbonline.org)
  • In addition to direct recruitment by RTKs, many signaling proteins are recruited by an alternative mechanism involving a family of membrane linked docking proteins such as FRS-2a, and b, IRS-1 and 2, and Gab-1 and 2, among many others. (yale.edu)
  • CD47 is a type I integral membrane protein with an extracellular immunoglobulin variable (IgV)-like domain, five membrane-spanning segments, and a short alternatively spliced carboxy-terminal cytoplasmic tail. (springer.com)
  • SIRPs are integral membrane proteins with important signaling functions, and CD47 serves as a counterreceptor for SIRPα. (springer.com)
  • A reduced miR-126 expression and an elevated Crk protein expression, alone or in combination, statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. (nih.gov)
  • The present study dissects how Agrin mediated signals from the extracellular matrix are sensed by tumor cells. (aacrjournals.org)
  • In addition, transient restoration of PTEN (or other proteins) to tumor cells that lack PTEN might induce a stronger initial phenotype, which might disappear during steady-state, stable expression. (biologists.org)
  • Importantly, some of these studies have demonstrated that STAT3 can function either as an oncoprotein or a tumor suppressor in the same cell type, depending on the specific genetic background or presence/absence of specific coexisting biochemical defects. (mdpi.com)
  • In the second half, we will summarize the evidence supporting that STAT3 can function as a tumor suppressor. (mdpi.com)
  • Lu/BCAM (Lutheran/basal cell-adhesion molecule, a glycoprotein) belongs to the immunoglobulin superfamily which contains both Lu blood group and BCAM tumor-associated antigens. (biomedcentral.com)
  • As other GPI linked proteins such as the carcinoembryonic antigen (CEA), one of the most used tumor markers, CRIPTO is able to reach the bloodstream. (prolekare.cz)
  • Still, tumorigenesis requires mutations in multiple loci: along with dominant mutations in oncogenes such as RTKs, tumorigenesis also requires loss-of-function mutations in tumor suppressors. (genetics.org)
  • The relationship between oncogenic tyrosine kinases and tumor suppressors, and the extent to which mutations in each cooperate to direct oncogenic growth, is not well understood. (genetics.org)
  • Once T cells are effectively primed, pro-inflammatory cytokines such as interferon (INF)-, and Treg cell signals such as CTLA4, induce IDO manifestation in DCs.16,19 This Nkx2-1 will lead to their conversion into tolerogenic DCs that can inhibit T-cell growth as well as the induction of adaptive Treg cells, which suppress T-cell responses, including those against tumors (Fig. 2). (cancercurehere.com)
  • However, evidence for CD47 signaling that relies exclusively on these peptides must be viewed with skepticism based on compelling evidence that the same peptides can induce signaling independent of CD47 (Soto-Pantoja et al. (springer.com)
  • One of the protein-protein interaction domains in nRTKs are the Src homology 2 (SH2) and 3 (SH3) domains. (wikipedia.org)
  • The National Heart, Lung, and Blood Institute Working Group has postulated the cardiorenal syndrome (CRS) as an interaction between the kidneys and the cardiovascular system in which therapy to relieve congestive heart failure (HF) symptoms is limited by the further worsening renal function. (intechopen.com)
  • Some of the best-characterized protein interaction domains involved in insulin signaling are the PH (pleckstrin homology), PTB (phosphotyrosine binding), SH2, and SH3 domains ( 1 ) (Table 1 ). (jci.org)
  • These interaction domains exist in the natural tertiary structure of proteins. (jci.org)
  • In other cases, the domains for interaction are created by posttranslational covalent modification of the protein. (jci.org)
  • Our data suggest that the FAK-IGF-1R protein interaction is an important target and disruption of this protein-protein interaction with a small molecule has a potential anti-neoplastic therapeutic effect. (ufl.edu)
  • A point mutation in this region, K227E, blocks the GTP-dependent interaction of PI 3-kinase p110alpha with Ras in vitro and the ability of Ras to activate PI 3-kinase in intact cells. (embl.de)
  • Using an in vitro reconstitution assay, it is shown that the interaction of Ras-GTP, but not Ras-GDP, with PI 3-kinase leads to an increase in its enzymatic activity. (embl.de)
  • Mapping of the complementary site of interaction on the p110 protein defined 88 amino acids in the N-terminal region of p110 which mediate the binding of this subunit to either the p85 alpha or the p85 beta proteins. (embl.de)
  • Rapidly growing knowledge about the protein-protein interaction (PPI) networks (interactome) for hosts and pathogens is beginning to be used to create network-based models [ 6 ]. (biomedcentral.com)
  • A proteomic interaction screen with PISP/PDZK11 identified the calcium transporting ATPase SERCA2, supporting a connection to calcium signaling. (pnas.org)
  • Except for homologous kinase domains ( Src Homology 1, or SH1 domains), and some protein- protein interaction domains (SH2 and SH3 domains), the PTK families share little structurally. (blogspot.com)
  • Background: TAZ is a transcriptional co-activator with a PDZ-binding motif that is regulated by its interaction with 14-3-3 proteins (1). (cellsignal.com)
  • Gab1 interacts with Crk and CrkL, two proteins with SH2 and SH3 protein interaction domains that couple to signaling further downstream. (broadinstitute.org)
  • Furthermore, unique to this family of proteins is a novel interaction region, the BPS (for B etween P H and S H2) domain. (biomedcentral.com)
  • Overexpression studies further demonstrated that the Grb7/Tie2 interaction was mediated by a multidocking site, tyrosine 1100, on Tie2. (biomedcentral.com)
  • Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein that plays a wide range of cellular functions including phagocytosis of apoptotic cells, anti-inflammation, tissue regeneration, and homeostasis. (frontiersin.org)
  • The effect of EGF is mediated by the RNA-binding protein Grb7 (growth factor receptor-bound protein 7), which serves as an adaptor for a specific mRNA-protein export complex and a translational regulator. (rupress.org)
  • Additionally, IGF-I has been shown to interact with other stimuli of SMCs replication, such as platelet-derived growth factor (PDGF), thrombin, and angiotensin-II, to enhance cellular responsiveness ( 2 , 7 , 8 ). (pnas.org)
  • Thus, Ras proteins are critical in stimulating cell growth and division. (ahajournals.org)
  • Discontinuation of hCG resulted in the reappearance of HIV transcripts and proteins, skin lesions, and growth failure resulting in death. (jci.org)
  • The monolyceride glycerol monolaurate (GML) inhibits both bacterial growth and T cell receptor (TCR)-induced signaling. (sciencemag.org)
  • Two related cellular proteins, p80 and p85 (cortactin), become phosphorylated on tyrosine in pp60src-transformed cells and in cells stimulated with certain growth factors. (sdbonline.org)
  • STAT3 belongs to a family of transcription factors that transduces the cellular signals from a host of cytokines and soluble growth factors such as the IL-6 family cytokines, epidermal growth factor and platelet-derived growth factor [ 1 , 2 ]. (mdpi.com)
  • Of the cellular PTKs with known functions, many, such as SRC , are involved in cell growth . (blogspot.com)
  • The loss of RGD1 function amplifies the phenotype due to the SLG1 deletion and the small-budded double-mutant cells die because of defects in cell wall structure and lysis upon bud growth. (sdbonline.org)
  • Growth factor receptor bound (Grb) proteins 7, 10 and 14 are a family of structurally related multi-domain adaptor proteins involved in a variety of biological processes. (biomedcentral.com)
  • All aspects of cellular motility and invasion are controlled by the Rho GTPases and are closely linked to signals from the extracellular environment, particularly in response to growth factors. (biomedcentral.com)
  • However, the Cdc42p binding domain was necessary for filamentous growth in response to nitrogen starvation and for an essential function that Ste20p shares with its isoform Cla4p during vegetative growth. (embopress.org)
  • Subcellular localization of wild‐type and mutant Ste20p fused to green fluorescent protein showed that the Cdc42p binding domain is needed to direct localization of Ste20p to regions of polarized growth. (embopress.org)
  • 2012 ). Subsequent biochemical studies expanded the intracellular targets of this inhibitory signaling to include cGMP-dependent protein kinase (cGK), endothelial nitric oxide synthase (eNOS, NOS3), and vascular endothelial growth factor receptor-2 (VEGFR2) (Rogers et al. (springer.com)
  • Defining the key steps that lead to the specificity in insulin signaling presents a major challenge to biochemical research, but the outcome should offer new therapeutic approaches for treatment of patients suffering from insulin-resistant states, including type 2 diabetes. (jci.org)
  • Better understanding of IGF biochemical signaling pathways is of utmost importance for developing therapies for breast cancer. (biomedcentral.com)
  • The detection of mechanical signals, and their integration into biochemical pathways, is integral to the cell's ability to sense, measure and respond to its physical surroundings. (mechanobio.info)
  • Stem cells interact with biochemical and biophysical signals in their extracellular environment. (biomedcentral.com)
  • In the stem cell niche, stem cells receive biochemical and biophysical signals, which dictate the cell fate in development or regeneration. (biomedcentral.com)
  • It remains unclear, however, how cells perceive the mechanical stimuli and transmit them into cellular biochemical signals. (royalsocietypublishing.org)
  • Database homology searches using zizimin1 and Dock180 reveal that they are members of a novel family present in a wide variety of eukaryotes that we refer to as the CZH proteins ( Fig. 1 , Table 1 , Table 2 ). (biologists.org)
  • TAZ shares homology with the WW domain of Yes-associated protein (YAP) (1). (cellsignal.com)