A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
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.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
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.
Agents that inhibit PROTEIN KINASES.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
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.
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.
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.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Established cell cultures that have the potential to propagate indefinitely.
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.
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
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.
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.
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.
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)
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
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.
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.
LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.
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.
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.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
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.
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
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.
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.
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.
Physiologically inactive substances that can be converted to active enzymes.
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.
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.
A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.
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.
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).
The rate dynamics in chemical or physical systems.
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.
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.
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).
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.
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.
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 enzymes
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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.
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.
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.
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.
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.
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.
Proteins prepared by recombinant DNA technology.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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.
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, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
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.
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.
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.
A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.
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.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
A cell line derived from cultured tumor 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.
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.
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.
Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-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.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
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).
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.
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.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
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.
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.
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.
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.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
Adherence of cells to surfaces or to other cells.
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.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
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.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing five different PDZ domains, and a carboxyl-terminal phosphatase domain. In addition to playing a role as a regulator of the FAS RECEPTOR activity this subtype interacts via its PDZ and FERM domains with a variety of INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS.
Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A Janus kinase subtype that is predominantly expressed in hematopoietic cell. It is involved in signaling from a broad variety of CYTOKINE RECEPTORS including ones that utilize the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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.
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.
A subcategory of protein tyrosine phosphatases that are bound to the cell membrane. They contain cytoplasmic tyrosine phosphatase domains and extracellular protein domains that may play a role in cell-cell interactions by interacting with EXTRACELLULAR MATRIX components. They are considered receptor-like proteins in that they appear to lack specific ligands.
A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
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.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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.
Elements of limited time intervals, contributing to particular results or situations.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.
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).)
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Proto-oncogene proteins fes are protein-tyrosine kinases with a central SH2 DOMAIN. It has been implicated in SIGNAL TRANSDUCTION PATHWAYS for CELL DIFFERENTIATION of a variety of cell types including MYELOID PROGENITOR CELLS. Fes proto-oncogene proteins also bind TUBULIN and promote MICROTUBULE assembly.
A subclass of receptor-like protein tryosine phosphatases that contain a short extracellular domain, a cytosolic kinase-interaction domain, and single protein tyrosine kinase domain.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
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.
A family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Salts and esters of the 14-carbon saturated monocarboxylic acid--myristic acid.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
The phosphoric acid ester of serine.
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)
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.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.
Transport proteins that carry specific substances in the blood or across cell membranes.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Compounds containing the PhCH= radical.
The sum of the weight of all the atoms in a molecule.
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.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
The structural and functional changes by which SPERMATOZOA become capable of oocyte FERTILIZATION. It normally requires exposing the sperm to the female genital tract for a period of time to bring about increased SPERM MOTILITY and the ACROSOME REACTION before fertilization in the FALLOPIAN TUBES can take place.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
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.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
An Eph family receptor found abundantly in tissues of epithelial origin. It is expressed in a diverse array of tissues during embryonic development, suggesting that it may play a role in embryogenesis. In adult tissues high levels of the receptor are expressed in the LUNG; SKIN; SMALL INTESTINE and OVARY.
A rare acute myeloid leukemia in which the primary differentiation is to BASOPHILS. It is characterized by an extreme increase of immature basophilic granulated cells in the bone marrow and blood. Mature basophils are usually sparse.
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.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
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)

Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. (1/14131)

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

Gene expression profiles in HTLV-I-immortalized T cells: deregulated expression of genes involved in apoptosis regulation. (2/14131)

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia, an acute and often fatal T-cell malignancy. A key step in HTLV-I-induced leukemigenesis is induction of abnormal T-cell growth and survival. Unlike antigen-stimulated T cells, which cease proliferation after a finite number of cell division, HTLV-I-infected T cells proliferate indefinitely (immortalized), thus facilitating occurrence of secondary genetic changes leading to malignant transformation. To explore the molecular basis of HTLV-I-induced abnormal T-cell survival, we compared the gene expression profiles of normal and HTLV-I-immortalized T cells using 'gene array'. These studies revealed a strikingly altered expression pattern of a large number of genes along with HTLV-I-mediated T-cell immortalization. Interestingly, many of these deregulated genes are involved in the control of programmed cell death or apoptosis. These findings indicate that disruption of the cellular apoptosis-regulatory network may play a role in the HTLV-I-mediated oncogenesis.  (+info)

All-trans-retinoic acid inhibits Jun N-terminal kinase by increasing dual-specificity phosphatase activity. (3/14131)

Jun N-terminal kinases (JNKs) are serine-threonine kinases that play a critical role in the regulation of cell growth and differentiation. We previously observed that JNK activity is suppressed by all-trans-retinoic acid (t-RA), a ligand for retinoic acid nuclear receptors (RARs), in normal human bronchial epithelial cells, which are growth inhibited by t-RA. In this study, we investigated the mechanism by which t-RA inhibits JNK and the possibility that this signaling event is blocked in non-small cell lung cancer (NSCLC) cells. Virtually all NSCLC cell lines are resistant to the growth-inhibitory effects of t-RA, and a subset of them have a transcriptional defect specific to retinoid nuclear receptors. We found that in NSCLC cells expressing functional retinoid receptors, serum-induced JNK phosphorylation and activity were inhibited by t-RA in a bimodal pattern, transiently within 30 min and in a sustained fashion beginning at 12 h. Retinoid receptor transcriptional activation was required for the late, but not the early, suppression of JNK activity. t-RA inhibited serum-induced JNK activity by blocking mitogen-activated protein (MAP) kinase kinase 4-induced signaling events. This effect of t-RA was phosphatase dependent and involved an increase in the expression of the dual-specificity MAP kinase phosphatase 1 (MKP-1). t-RA did not activate MKP-1 expression or inhibit JNK activity in a NSCLC cell line with retinoid receptors that are refractory to ligand-induced transcriptional activation. These findings provide the first evidence that t-RA suppresses JNK activity by inhibiting JNK phosphorylation. Retinoid receptor transcriptional activation was necessary for the sustained inhibition of JNK activity by t-RA, and this signaling event was disrupted in NSCLC cells with retinoid receptors that are refractory to ligand-induced transcriptional activation.  (+info)

Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein. (4/14131)

The protein tyrosine kinase PYK2 has been implicated in signaling pathways activated by G-protein-coupled receptors, intracellular calcium, and stress signals. Here we describe the molecular cloning and characterization of a novel family of PYK2-binding proteins designated Nirs (PYK2 N-terminal domain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bind to the amino-terminal domain of PYK2 via a conserved sequence motif located in the carboxy terminus. The primary structures of Nirs reveal six putative transmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of the Drosophila retinal degeneration B protein (rdgB), a protein implicated in the visual transduction pathway in flies. We demonstrate that Nirs are calcium-binding proteins that exhibit PI transfer activity in vivo. Activation of PYK2 by agents that elevate intracellular calcium or by phorbol ester induce tyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similar expression patterns in several regions of the brain and retina. In addition, PYK2-Nir complexes are detected in lysates prepared from cultured cells or from brain tissues. Finally, the Nir1-encoding gene is located at human chromosome 17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family of evolutionarily conserved PYK2-binding proteins that play a role in the control of calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors.  (+info)

Identification of a new Pyk2 target protein with Arf-GAP activity. (5/14131)

Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells. Immunofluorescence experiments demonstrate that Pap is localized in the Golgi apparatus and at the plasma membrane, where it is colocalized with Pyk2. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of recombinant Pap protein to Golgi preparations prevented Arf-dependent generation of post-Golgi vesicles in vitro. Moreover, overexpression of Pap in cultured cells reduced the constitutive secretion of a marker protein. We propose that Pap functions as a GAP for Arf and that Pyk2 may be involved in regulation of vesicular transport through its interaction with Pap.  (+info)

Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. (6/14131)

Shp-2 is an SH2 domain-containing protein tyrosine phosphatase. Although the mechanism remains to be defined, substantial experimental data suggest that Shp-2 is primarily a positive regulator in cell growth and development. We present evidence here that Shp-2, while acting to promote mitogenic signals, also functions as a negative effector in interferon (IFN)-induced growth-inhibitory and apoptotic pathways. Treatment of mouse fibroblast cells lacking a functional Shp-2 with IFN-alpha or IFN-gamma resulted in an augmented suppression of cell viability compared to that of wild-type cells. To dissect the molecular mechanism, we examined IFN-induced activation of signal transducers and activators of transcription (STATs) by electrophoretic mobility shift assay, using a specific DNA probe (hSIE). The amounts of STAT proteins bound to hSIE upon IFN-alpha or IFN-gamma stimulation were significantly increased in Shp-2(-/-) cells. Consistently, tyrosine phosphorylation levels of Stat1 upon IFN-gamma treatment and, to a lesser extent, upon IFN-alpha stimulation were markedly elevated in mutant cells. Furthermore, IFN-gamma induced a higher level of caspase 1 expression in Shp-2(-/-) cells than in wild-type cells. Reintroduction of wild-type Shp-2 protein reversed the hypersensitivity of Shp-2(-/-) fibroblasts to the cytotoxic effect of IFN-alpha and IFN-gamma. Excessive activation of STATs by IFNs was also diminished in mutant cells in which Shp-2 had been reintroduced. Together, these results establish that Shp-2 functions as a negative regulator of the Jak/STAT pathway. We propose that Shp-2 acts to promote cell growth and survival through two mechanisms, i.e., the stimulation of growth factor-initiated mitogenic pathways and the suppression of cytotoxic effect elicited by cytokines, such as IFNs.  (+info)

Increased expression of fibroblast growth factor 8 in human breast cancer. (7/14131)

Fibroblast growth factor 8 (FGF8) is an important developmental protein which is oncogenic and able to cooperate with wnt-1 to produce mouse mammary carcinoma. The level of expression of FGF8 mRNA was measured in 68 breast cancers and 24 non-malignant breast tissues. Elevated levels of FGF8 mRNA were found in malignant compared to non-malignant breast tissues with significantly more malignant tissues expressing FGF8 (P=0.019) at significantly higher levels (P=0.031). In situ hybridization of breast cancer tissues and analysis of purified populations of normal epithelial cells and breast cancer cell lines showed that malignant epithelial cells expressed FGF8 mRNA at high levels compared to non-malignant epithelial and myoepithelial cells and fibroblasts. Although two of the receptors which FGF8 binds to (FGFR2-IIIc, FGFR3-IIIc) are not expressed in breast cancer cells, an autocrine activation loop is possible since expression of fibroblast growth factor receptor (FGFR) 4 and FGFR1 are retained in malignant epithelial cells. This is the first member of the FGF family to have increased expression in breast cancer and a potential autocrine role in its progression.  (+info)

Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. (8/14131)

Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3, is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express high levels of the antiapoptotic protein Bcl-xL. Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-xL expression and induces apoptosis, demonstrating that Stat3 signaling is essential for the survival of myeloma tumor cells. These findings provide evidence that constitutively activated Stat3 signaling contributes to the pathogenesis of multiple myeloma by preventing apoptosis.  (+info)

T cell development in the thymus produces multiple lineages of cells, including conventional naïve CD4+ and CD8+ T cells, regulatory T cells, and innate T cells. Innate T cells encompass γδ T cells, invariant natural killer (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and H2-M3-restricted cells (Berg, 2007). Although they are a minor subset of all thymocytes, innate T cells develop in the thymus and share characteristics of the innate and adaptive immune systems (Berg, 2007). These lymphocytes undergo antigen receptor rearrangement and are able to exert their effector function immediately upon ex vivo stimulation (Berg, 2007). However, in several strains of mice harboring mutations in T cell signaling proteins or transcriptional regulators, conventional CD8+ T cells develop as innate cells that share characteristics with memory T cells (Atherly et al., 2006b; Broussard et al., 2006; Fukuyama et al., 2009; Gordon et al., 2011; Verykokakis et al., 2010b; Weinreich et al., 2010). One of
Autor: Volberg, T. et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2001-06; Keywords: Animals; Cell Adhesion Molecules/metabolism; Cell Line; Cell-Matrix Junctions/drug effects/enzymology/*metabolism; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions/drug effects/enzymology/metabolism; Gene Deletion; Mice; Microfilament Proteins/metabolism; Microscopy, Fluorescence; Phosphorylation/drug effects; Phosphotyrosine/metabolism; Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism; Proto-Oncogene Proteins c-fyn; Proto-Oncogene Proteins c-yes; Proto-Oncogene Proteins pp60(c-src)/antagonists &; inhibitors/genetics/*metabolism; Tyrphostins/pharmacology; src-Family Kinases/antagonists & inhibitors/*metabolism; Titel: pp60(c-src) and related tyrosine kinases: a role in the assembly and reorganization of matrix adhesions
TY - JOUR. T1 - Bi-directional regulation between tyrosine kinase Etk/BMX and tumor suppressor p53 in response to DNA damage. AU - Jiang, Tianyun. AU - Guo, Zhiyong. AU - Dai, Bojie. AU - Kang, Miyoung. AU - Ann, David K.. AU - Kung, Hsing Jien. AU - Qiu, Yun. PY - 2004/11/26. Y1 - 2004/11/26. N2 - Etk/Bmx, a member of the Tec family of nonreceptor tyrosine kinases, has been implicated in the regulation of various cellular processes including proliferation, differentiation, motility, and apoptosis. Here, we report the identification of Tec family kinases as the potential interacting proteins of the tumor suppressor p53 by an Src homology 3 domain array screening. Etk is physically associated with p53 through its Src homology 3 domain and the proline-rich domain of p53. Induction of p53 expression by DNA damage inhibits Etk activity in several cell types. Down-regulation of Etk expression by a specific small interfering RNA sensitizes prostate cancer cells to doxorubicin-induced apoptosis, ...
Proteins encoded by oncogenes such as v-fps/fes, v-src, v-yes, v-abl, and v-fgr are cytoplasmic protein tyrosine kinases which, unlike transmembrane receptors, are localized to the inside of the cell. These proteins possess two contiguous regions of sequence identity: a C-terminal catalytic domain of 260 residues with homology to other tyrosine-specific and serine-threonine-specific protein kinases, and a unique domain of approximately 100 residues which is located N terminal to the kinase region and is absent from kinases that span the plasma membrane. In-frame linker insertion mutations in Fujinami avian sarcoma virus which introduced dipeptide insertions into the most stringently conserved segment of this N-terminal domain in P130gag-fps impaired the ability of Fujinami avian sarcoma virus to transform rat-2 cells. The P130gag-fps proteins encoded by these transformation-defective mutants were deficient in protein-tyrosine kinase activity in rat cells. However v-fps polypeptides derived
TY - JOUR. T1 - Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3-kinase and is involved in interleukin 6- induced neuroendocrine differentiation of prostate cancer cells. AU - Qiu, Y.. AU - Robinson, D.. AU - Pretlow, T. G.. AU - Kung, H. J.. PY - 1998/3/31. Y1 - 1998/3/31. N2 - Etk/Bmx is the newest member of Btk tyrosine kinase family that contains a pleckstrin homology domain, an src homology 3 domain, an src homology 2 domain, and a catalytic domain. Unlike other members of the Btk family kinases, which are mostly hemopoietic cell-specific, Etk/Bmx is preferentially expressed in epithelial and endothelial cells. We first identified this kinase in prostate cancer [Robinson, D., He, F, Pretlow, T. and Kung, H. J. (1996) Proc. Natl. Acad. Sci. USA 93, 5958-5962). Here we report that Etk is engaged in phosphatidylinositol 3-kinase (PI3-kinase) pathway and plays a pivotal role in interleukin 6 (IL-6) signaling in a prostate cancer cell line, ...
The Tec family tyrosine kinases regulate lymphocyte development, activation, and differentiation. In T cells, the predominant Tec kinase is Itk, which functions downstream of the T-cell receptor to regulate phospholipase C-γ. This review highlights recent advances in our understanding of Itk kinase structure and enzymatic regulation, focusing on Itk protein domain interactions and mechanisms of substrate recognition. We also discuss the role of Itk in the development of conventional versus innate T-cell lineages, including both αβ and γδ T-cell subsets. Finally, we describe the complex role of Itk signaling in effector T-cell differentiation and the regulation of cytokine gene expression. Together, these data implicate Itk as an important modulator of T-cell signaling and function.
The Tec-family protein tyrosine kinase IL-2-inducible T cell kinase (ITK) mediates T cell activation, as does the adaptor protein SLP-76 (SH2-domain-containing leukocyte protein of 76 kD), which forms a complex with ITK and other intracellular signaling enzymes. One of these enzymes is phospholipase C-γ1 (PLC-γ1), which mediates T cell receptor (TCR)-stimulated intracellular calcium mobilization leading to the activation of transcription factors such as nuclear factor of activated T cells. The Src-family tyrosine kinase Lck and the Syk-family tyrosine kinase ζ chain-associated protein kinase of 70 kD (ZAP-70), together with ITK, are necessary for the phosphorylation of PLC-γ1 in response to TCR stimulation. ITK is thought to phosphorylate a specific tyrosine residue of PLC-γ1 that is required for its activation. The mechanism of activation of ITK appears to involve the interaction between SLP-76 and ITK, which not only initiates ITK activity but is also important to maintain the kinase ...
The genetics of peripheral T cell lymphomas (PTCL) are poorly understood. Recently, a chromosomal translocation, t(5;9)(q33;q22), was discovered in a rare subset of PTCL with a follicular growth pattern. This translocation involved the SYK (Spleen tyrosine kinase) and ITK (Inducible T cell kinase) genes and generated an ITK-SYK fusion protein. The functional attributes of ITK-SYK are thus far uncharacterised. Here we demonstrate that ITK-SYK is an active tyrosine kinase, the expression of which resulted in ERK activation in 293T cells and transformation of NIH-3T3 cells, inducing loss of contact inhibition and formation of anchorage-independent colonies in soft agar. These observations were a direct result of the kinase activity of ITK-SYK as a kinase dead mutant was unable to induce NIH-3T3 transformation or phosphorylation of ERK. ITK-SYK is unusual amongst fusion tyrosine kinases (FTKs) as it does not contain a known oligomerisation domain but does have an N-terminal ...
Chronic graft-versus-host disease (cGVHD) is a life-threatening impediment to allogeneic hematopoietic stem cell transplantation, and current therapies do not completely prevent and/or treat cGVHD. CD4+ T cells and B cells mediate cGVHD; therefore, targeting these populations may inhibit cGVHD pathogenesis. Ibrutinib is an FDA-approved irreversible inhibitor of Brutons tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) that targets Th2 cells and B cells and produces durable remissions in B cell malignancies with minimal toxicity. Here, we evaluated whether ibrutinib could reverse established cGVHD in 2 complementary murine models, a model interrogating T cell-driven sclerodermatous cGVHD and an alloantibody-driven multiorgan system cGVHD model that induces bronchiolar obliterans (BO). In the T cell-mediated sclerodermatous cGVHD model, ibrutinib treatment delayed progression, improved survival, and ameliorated clinical and pathological manifestations. In the alloantibody-driven cGVHD ...
Accepted name: non-specific protein-tyrosine kinase. Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Other name(s): ABL; ABL1; ABL2; ABLL; ACK1; ACK2; AGMX1; ARG; ATK; ATP:protein-tyrosine O-phosphotransferase (ambiguous); BLK; Bmk; BMX; BRK; Brutons tyrosine kinase; Bsk; BTK; BTKL; CAKb; Cdgip; CHK; CSK; CTK; CYL; cytoplasmic protein tyrosine kinase; EMT; ETK; Fadk; FAK; FAK2; FER; Fert1/2; FES; FGR; focal adhesion kinase; FPS; FRK; FYN; HCK; HCTK; HYL; IMD1; ITK; IYK; JAK1; JAK2; JAK3; Janus kinase 1; Janus kinase 2; Janus kinase 3; JTK1; JTK9; L-JAK; LCK; LSK; LYN; MATK; Ntk; p60c-src protein tyrosine kinase; PKB; protein-tyrosine kinase (ambiguous); PSCTK; PSCTK1; PSCTK2; PSCTK4; PSCTK5; PTK2; PTK2B; PTK6; PYK2; RAFTK; RAK; Rlk; Sik; SLK; SRC; SRC2; SRK; SRM; SRMS; STD; SYK; SYN; Tck; TEC; TNK1; Tsk; TXK; TYK2; TYK3; YES1; YK2; ZAP70. Systematic name: ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific). Comments: Unlike EC, receptor ...
HIV replication in macrophages contributes to the latent viral reservoirs, which are considered the main barrier to HIV eradication. Few cellular factors that facilitate HIV replication in latently infected cells are known. We previously identified cyclin L2 as a critical factor required by HIV-1 and found that depletion of cyclin L2 attenuates HIV-1 replication in macrophages. Here we demonstrate that cyclin L2 promotes HIV-1 replication through interactions with the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Cyclin L2 and DYRK1A were colocalized in the nucleus and were found together in immunoprecipitation experiments. Knockdown or inhibition of DYRK1A increased HIV-1 replication in macrophages, while depletion of cyclin L2 decreased HIV-1 replication. Furthermore, depletion of DYRK1A increased expression levels of cyclin L2. DYRK1A is a proline-directed kinase that phosphorylates cyclin L2 at serine residues. Mutations of cyclin L2 at serine residues preceding ...
Prot #PCYC-1112-CA: A Randomized, Multicenter, Open-label, Phase 3 Study of the Brutons Tyrosine Kinase (BTK) Inhibitor Ibrutinib versus Ofatumumab in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic ...
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. ...
https://astx.com/wp-content/uploads/2019/11/logo_white.png 0 0 webadmin https://astx.com/wp-content/uploads/2019/11/logo_white.png webadmin2007-12-17 13:07:252016-11-28 13:35:12SuperGen Reports Initiation of Multi-arm Phase 1b Trial of Novel Tyrosine Kinase Inhibitor ...
The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimuli. This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia. Ischemia-induced Src activation is followed by phosphorylation of PP2A at Tyr307 leading to its inhibition in the rat hippocampus. SU6656, a Src inhibitor, up-regulates PP2A activity, resulting in a significant decreased activity in ERK and its targets, CREB and ERα. In addition, the PP2A inhibitor, cantharidin, led to an up-regulation of ERK activity and was able to counteract Src inhibition during ischemia. Src induces up-regulation of ERK activity and its target transcription factors, CREB and ERα, through attenuation of PP2A activity. Therefore, activation of ERK is the result of a crosstalk between two pathways, Raf-dependent
Itk, a Tec family tyrosine kinase, acts downstream of Lck and phosphatidylinositol 3-kinase to facilitate T cell receptor (TCR)-dependent calcium influxes and increases in extracellular-regulated kinase activity. Here we demonstrate interactions between Itk and crucial components of TCR-dependent signaling pathways. First, the inositide-binding pocket of the Itk pleckstrin homology domain directs the constitutive association of Itk with buoyant membranes that are the primary site of TCR activation and are enriched in both Lck and LAT. This association is required for the transphosphorylation of Itk. Second, the Itk proline-rich region binds to Grb2 and LAT. Third, the Itk Src homology (SH3) 3 and SH2 domains interact cooperatively with Syk-phosphorylated SLP-76. Notably, SLP-76 contains a predicted binding motif for the Itk SH2 domain and binds to full-length Itk in vitro. Finally, we show that kinase-inactive Itk can antagonize the SLP-76-dependent activation of NF-AT. The inhibition of NF-AT
It also includes a pipeline of several preclinical candidates such as additional JAK inhibitors known as soft JAK inhibitors, as well as inhibitors of the MK-2 signalling pathway and inhibitors of interleukin-2-inducible T cell kinase ...
Catalytic domain of the Protein Tyrosine Kinases, Srm and Brk. Protein Tyrosine Kinase (PTK) family; Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and breast tumor kinase (Brk, also called protein tyrosine kinase 6); catalytic (c) domains. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk are a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) tyr kinases. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively ...
TY - JOUR. T1 - The cytosolic domain of protein-tyrosine kinase 7 (PTK7), generated from sequential cleavage by a disintegrin and metalloprotease 17 (ADAM17) and γ-secretase, enhances cell proliferation and migration in colon cancer cells. AU - Na, Hye Won. AU - Shin, Won Sik. AU - Ludwig, Andreas. AU - Lee, Seung Taek. PY - 2012/7/20. Y1 - 2012/7/20. N2 - Protein-tyrosine kinase 7 (PTK7) is a member of the defective receptor protein-tyrosine kinases and is known to function as a regulator of planar cell polarity during development. Its expression is up-regulated in some cancers including colon carcinomas. A 100-kDa fragment of PTK7 was detected in the culture media from colon cancer cells and HEK293 cells. The shed fragment was named sPTK7-Ig1-7 because its molecular mass was very similar to that of the entire extracellular domain of PTK7 that contains immunoglobulin-like loops 1 to 7 (Ig1-7). The shedding of sPTK7-Ig1-7 was enhanced by treatment with phorbol 12-myristate 13-acetate. In ...
PYK2 (PTK2B protein tyrosine kinase 2 beta) is a cytoplasmic protein tyrosine kinase. It is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. PYK2 may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK and the SH2 domain of GRB2. This protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies ...
Tyrosine Protein Kinase SYK - Pipeline Review, H2 2020 Summary Tyrosine Protein Kinase SYK (Spleen Tyrosine Kinase or p72 Syk or ...
IntroductionFyn (p59fyn) is a membrane-associated non-receptor protein tyrosine kinase of approximately 59kDa, which belongs to the Src family of…
Objective The multikinase inhibitor META060 has been shown to inhibit NF-,B activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. Methods Glycogen synthase kinase 3, (GSK3,),dependent ,-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1, (IL-1,),mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. Results META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Brutons tyrosine kinase ...
BLNK: a central linker protein in B cell activation, 1998), activating its interaction sites and binding itself to BLNK. This protein lacks of catalytic activity; its task is to facilitate the protein-protein and protein-cytoplasmic membrane interaction among those elements involved in the initial phase of this signaling pathway (Adapter proteins in lymphocyte antigen-receptor signaling, 2000). BLNK can anchors itself to the cytoplasmic membrane thank to a leucine motif located on its N-terminal. When the B Cell Receptor (BCR) is activated, occurs a chain of events that actives the phosphatidylinositol-3 kinase (PI 3 K) which generates PIP 3 (Signalling of Brutons tyrosine kinase, Btk, 1999). It binds Btk, through the PH domain (A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains, 1997), causing its transfer from the cytosol to the cytoplasmic membrane; this process is facilitated by BLNK through its SH2 domain. Furthermore BLNK recruits the PLCγ2 ...
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase. Protein Tyrosine Kinase (PTK) family; Anaplastic Lymphoma Kinase (ALK) and Leukocyte Tyrosine (tyr) Kinase (LTK); catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor tyr kinases (RTKs) whose ligands are not yet well-defined. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. ALK appears to play an important role in mammalian neural development as well as visceral muscle ...
This is a Phase II, open-label, multi-center trial designed primarily to evaluate the rate of complete or major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow, in patients with CML who are refractory to or intolerant of interferon-alpha.. During the core phase of the study, patients will receive once daily oral administration of STI571 at a dose of 400 mg, for up to 12 months. After completing 12 months of therapy patients may be eligible to receive additional therapy provided that, in the opinion of the investigator, the patient has benefited from treatment with STI571 and in the absence of safety concerns. Patients will receive STI571 on an outpatient basis.. During the extended phase (which is of indefinite duration), patients may continue STI571 until either progression to accelerated phase, blast phase, death, the development of intolerable toxicity, or the investigator feels it is no longer in the patients ...
Signalling pathways regulate development and homeostasis but their importance extends beyond normal physiological conditions, as mutations that ectopically activate or repress a signalling pathway are the cause of many human diseases. Protein tyrosine kinases are key elements of signal transduction in most pathways. In some cases, as in the EGF pathway, the transmembrane receptor itself has tyrosine kinase activity; in other cases, such as the JAK/STAT pathway, the intracellular domain of the receptor associates to a cytoplasmic tyrosine kinase.. The JAK/STAT pathway has been conserved during evolution, allowing Drosophila melanogaster to be used as a simplified model for signal transduction. In Drosophila, the pathway elements comprise only three ligands (Upd, Upd2 and Upd3), one homodimeric receptor (Dome), one JAK kinase (Hop) and one STAT transcription factor (STAT92E) (Arbouzova and Zeidler, 2006). This contrasts with the complexity found in mammals where multiple ligands and heterodimeric ...
Zhou, Q., Phoa, A., Abbassi, R., Hoque, M., Reekie, T., Font Sadurni, J., Ryan, R., Stringer, B., Day, B., Johns, T., Munoz, L., Kassiou, M. (2017). Structural optimization and pharmacological evaluation of inhibitors targeting dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) and CDC-like kinases (CLK) inglioblastoma. Journal of Medicinal Chemistry, 60(5), 2052-2070. [More Information] ...
ATP binding ,integrin binding ,non-membrane spanning protein tyrosine kinase activity ,phosphatase binding phosphotyrosine residue binding ,protein kinase activity ,protein kinase binding ,protein serine/threonine kinase activity ,protein tyrosine kinase activity ,SH2 domain binding ,signal transducer, downstream of receptor, with protein tyrosine kinase activity ,Toll-like receptor ...
NeoGenomics has launched the NeoLAB Solid Tumor Monitor and NeoLAB Bruton Tyrosine Kinase (BTK) Inhibitor Acquired Resistance test. Each new test uses cell-free DNA from peripheral blood plasma to quantify and track genomic abnormalities in the tumors of cancer patients. Resistance to BTK inhibitors is associated with mutations in the BTK and PLCG2 genes. The test is capable of detecting mutations in these two genes prior to tissue or cell-based testing. The test can be used to monitor patients treated with BTK inhibitors, especially in chronic lymphocytic leukemia, mantle cell lymphoma, and diffuse large B-cell lymphoma, and to alert physicians to mutations in BTK and PLCG2 that may indicate early resistance to BTK inhibitor treatment.
SYK (Spleen tyrosine kinase), along with Zap-70, is a member of the Syk family of cytoplasmic tyrosine kinases that contain a dual SH2 domain separated by a linker region. In B cells, SYK couples the B-cell antigen receptor (BCR) to the mobilization of calcium ion either through a phosphoinositide 3-kinase-dependent pathway, when not phosphorylated on tyrosines of the linker region, or through phosphorylation/activation of phospholipase C-gamma, when phosphorylated on Tyr-348 and Tyr-352. Phosphorylation on Tyr-323 creates a binding site for c-Cbl, which is a negative regulator of BCR-stimulated calcium signaling. Also transmits signals from other cell surface receptors including the T-cell receptor, CD74, Fc receptor, and integrins. Abnormal constitutive SYK activity has been implicated in some hematopoietic malignancies ...
The IUPHAR/BPS Guide to Pharmacology. BMX non-receptor tyrosine kinase - Tec family. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
The present invention relates to compounds of the Formula I, the pharmaceutically acceptable salts and stereoisomers thereof, which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions in mammals: wherein n is an integer, preferably n is 1; wherein R1 and R2 are independently selected from the group consisting of:
A novel form of receptor-kinase interaction was first described in the interaction between the CD4 and CD8 antigens and the protein-tyrosine kinase p56lck. This linkage, between a regulatory antigen on T cells and a member of a family of intracellular molecules with an established ability to activate and transform cells, is likely to be of great importance in the regulation of T-cell growth. Recently, data have been obtained on the molecular basis of regulation of the CD4/CD8-p56lck interaction and an interaction between the T-cell receptor complex (TCR-CD3) and another src-kinase p59fyn has been described. Here, Christopher Rudd examines these interactions and outlines their potential roles in normal and malignant T-cell growth.
|p|Brutons tyrosine kinase (BTK) is a Tec family kinase that plays a critical role in B cell development. Upon B cell receptor engagement, BTK translocates to the plasma membrane, where it is transphosphorylated by LYN and SYK kinases at Tyr 551. This initial phosphorylation event is followed by au
This book is the first one written about the JAK/STAT pathway. The JAK (Janus Kinase) Protein tyrosine kinases are novel phosphotransferases absolutely required for cellular signalling downstream of n
Cytosolic compartmentalization through liquid-liquid unmixing, such as the formation of RNA granules, is involved in many cellular processes and might be used to regulate signal transduction. However, specific molecular mechanisms by which liquid-liquid unmixing and signal transduction are coupled r …
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a
Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to
Fingerprint Dive into the research topics of Identification, cloning, and characterization of a novel human T-cell- specific tyrosine kinase located at the hematopoietin complex on chromosome 5q. Together they form a unique fingerprint. ...
Chronic GVHD develops from coordinated effects of both B and T cells, and multiple key functions of these cells are driven by TEC family kinases. Here, we show that neither XID BM nor Itk-/- donor T cells facilitate the development of systemic cGVHD in mice, identifying the importance of the TEC kinases BTK and ITK in cGVHD and identifying these 2 enzymes as therapeutic targets in this disease. Therefore, because of its ability to simultaneously target BTK and ITK, ibrutinib holds specific promise for the treatment of cGVHD. Our studies utilize 2 distinct but complementary, validated murine models of cGVHD: one that has dominant sclerodermatous features and the other with a nonsclerodermatous, multiorgan system fibrotic disease with BO (32, 33). Our results indicate that ibrutinib targets B and T cell-driven GC responses and is remarkably effective in treating cGVHD. In the sclerodermatous model, animals receiving therapeutic ibrutinib were often indistinguishable from their healthy ...
The Breast tumor kinase Brk is a prototypical non-myristoylated, non-receptor tyrosine kinase. Brk expression is epithelial-specific and ,in normal tissues, restricted to cells exiting the cell cycle and undergoing terminal differentiation. To determine the biological role of Brk in the gastrointestinal tract, we disrupted mouse brk by homologous recombination. Loss of Brk in the mouse resulted in increased intestinal epithelial cell turnover and the appearance of longer small intestinal villi. Brk deficient mice displayed enhanced accumulation of nuclear (-catenin and upregulation of the (-catenin target gene c-myc in the crypt compartment of small and large intestine. In addition, Brk deficient mice exhibited increased Akt kinase activity. Even though, there was no corresponding difference in base-line apoptosis in untreated wild-type and knockout animals. However, subjected to (-irradiation, Brk deficient animals were significantly impaired in the apoptotic response. Wild-type mice, however, ...
This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kise (DYRK) family. This member contains a nuclear targeting…
This gene encodes a member of the Dual-specificity tyrosine phosphorylation-regulated kise (DYRK) family. This member contains a nuclear targeting…
TY - JOUR. T1 - Docking-based substrate recognition by the catalytic domain of a protein tyrosine kinase, C-terminal Src kinase (Csk). AU - Lee, Sungsoo. AU - Ayrapetov, Marina K.. AU - Kemble, David J.. AU - Parang, Keykavous. AU - Sun, Gongqin. PY - 2006/3/24. Y1 - 2006/3/24. N2 - Protein tyrosine kinases are key enzymes of mammalian signal transduction. Substrate specificity is a fundamental property that determines the specificity and fidelity of signaling by protein tyrosine kinases. However, how protein tyrosine kinases recognize the protein substrates is not well understood. C-terminal Src kinase (Csk) specifically phosphorylates Src family kinases on a C-terminal Tyr residue, which down-regulates their activities. We have previously determined that Csk recognizes Src using a substrate-docking site away from the active site. In the current study, we identified the docking determinants in Src recognized by the Csk substrate-docking site and demonstrated an interaction between the docking ...
BTKFP : Two separate EDTA specimens and the patient information sheet are required.   Specimen Type: Blood for BTKSP / Bruton Tyrosine Kinase (BTK) Genotype, Full Gene Sequence Container/Tube: Lavender top (EDTA) Specimen Volume: 3 mL Collection Instructions: 1. Send specimen in original tube. 2. Label as BTKSP. Specimen Stability Information: Refrigerated (preferred)/Ambient   Specimen Type: Blood for BTK / Bruton Tyrosine Kinase (Btk), Protein Expression, Flow Cytometry, Blood Container/Tube: Lavender top (EDTA) Specimen Volume: 4 mL Collection Instructions: 1. Send specimen in original tube. Do not aliquot. 2. Ship at ambient temperature only. 3. Label as BTK. Specimen Stability Information: Ambient 72 hours Additional Information: For flow cytometry serial monitoring, we recommend that specimen draws be performed at the same time of day.
Looking for online definition of protein-tyrosine kinases in the Medical Dictionary? protein-tyrosine kinases explanation free. What is protein-tyrosine kinases? Meaning of protein-tyrosine kinases medical term. What does protein-tyrosine kinases mean?
TY - JOUR. T1 - Genomic organization of mouse and human Brutons agammaglobulinemia tyrosine kinase (Btk) loci. AU - Sideras, Paschalis. AU - Müller, Susanne. AU - Shiels, Helena. AU - Jin, Hong. AU - Khan, Wasif N.. AU - Nilsson, Lars. AU - Parkinson, Emma. AU - Thomas, Jeffrey D.. AU - Brandén, Lars. AU - Larsson, Irene. AU - Paul, William E.. AU - Rosen, Fred S.. AU - Alt, Fredrick W.. AU - Vetrie, David. AU - Smith, C. I.Edvard. AU - Xanthopoulos, Kleanthis G.. PY - 1994/12/15. Y1 - 1994/12/15. N2 - Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 ...
Title:The 2010 Patent Landscape for Spleen Tyrosine Kinase Inhibitors+. VOLUME: 6 ISSUE: 2. Author(s):Alessandro F. Moretto, Christoph Dehnhardt, Neelu Kaila, Nikolaos Papaioannou and Atli Thorarensen. Affiliation:Inflammation and Immunology Medicinal Chemistry Pfizer, 200 Cambridgepark Drive, Cambridge MA 02140 USA.. Keywords:Anti-inflammatory pathway, non-receptor tyrosine kinase, rheumatoid arthritis, SYK, SYK inhibitor, SYK-patents. Abstract:Discovery of small molecular inhibitors for treatment of rheumatoid arthritis is a major ongoing effort within the pharmaceutical industry. Spleen tyrosine kinase (SYK) is one of leading small molecular targets with regard to clinical development primarlly due to efforts by Rigel and Portola. In this review, we provide a comprehensive overview of the SYK patent landscape. The patent literature we evaluated relates to any organization that has filed applications that imply that SYK is the intended target. The interest in SYK was initiated in the early ...
To study the importance of PLC-γ for the mitogenic potential of NPM-ALK we selected Rat-1 fibroblasts and the lymphocyte cell line Ba/F3 as model systems. Since NPM-ALK is associated with lymphomas, this lymphocyte cell line rather than fibroblasts might better represent the in vivo target of this oncogene. In Rat-1 fibroblasts NPM-ALK-induced soft-agar growth was severely impaired by mutation of the PLC-γ binding site. Ba/F3 cells depend on IL-3 for their growth, and this growth factor dependence could be overcome by the expression of the kinase-active wt NPM-ALK. As mentioned above, mutation of the IRS-1(Tyr156) or SHC(Tyr567) binding sites in NPM-ALK did not lead to the loss of growth factor-independent growth by these lymphocytes. Most importantly, however, mutation of the PLC-γ binding site in NPM-ALK(Tyr664) was sufficient to block factor-independent proliferation of these lymphocytes. We obtained mass clones expressing NPM-ALK(Y664F) and three independent single clones by limiting ...
BTKFP : X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency affecting males in approximately 1 in 200,000 live births. XLA is caused by variants in the Bruton tyrosine kinase gene (BTK),(1) which results in a profound block in B-cell development within the bone marrow and a significant reduction, or complete absence, of mature B cells in peripheral blood.(2) Approximately 85% of male patients with defects in early B-cell development have XLA.(3) Due to the lack of mature B cells, XLA patients have markedly reduced levels of all major classes of immunoglobulins in the serum and are, therefore, susceptible to severe and recurrent bacterial infections. Pneumonia, otitis media, enteritis, and recurrent sinopulmonary infections are among the key clinical diagnostic characteristics of the disease. The spectrum of infectious complications also includes enteroviral meningitis, septic arthritis, cellulitis, and empyema, among others. The disease typically manifests in male children younger
A novel approach to design selective spleen tyrosine kinase (Syk) inhibitors is described. Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of autoimmune diseases such as asthma, rheumatoid arthritis,
TY - JOUR. T1 - Phosphoinositide 3-kinase and Brutons tyrosine kinase regulate overlapping sets of genes in b lymphocytes. AU - Fruman, David A.. AU - Ferl, Gregory Z.. AU - An, Sam S.. AU - Donahue, Amber C.. AU - Satterthwaite, Anne B.. AU - Witte, Owen N.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2002/1/8. Y1 - 2002/1/8. N2 - Brutons tyrosine kinase (Btk) acts downstream of phosphoinositide 3-kinase (P13K) in a pathway required for B cell receptor (BCR)-dependent proliferation. We used DNA microarrays to determine what fraction of genes this pathway influences and to investigate whether P13K and Btk mediate distinct gene regulation events. As complete loss-of-function mutations in P13K and Btk alter B cell subpopulations and may cause compensatory changes in gene expression, we used B cells with partial loss of function in either P13K or Btk. Only about 5% of the BCR-dependent gene expression changes were significantly affected by reduced P13K or Btk. The ...
Spleen Tyrosine Kinase (SYK) was recently recognized as a fresh target in acute myeloid leukemia (AML); however, its mechanistic part in this disease is definitely poorly recognized. of a fusion of to in a patient with MDS with capital t(9;12)(q22;p12).12 Importantly, this TEL-SYK fusion transforms the interleukin-3 (IL-3) dependent murine hematopoietic cell collection Ba/F3 to growth element independence.12 We recognized AML as another hematologic malignancy in which SYK takes on an important part.3 While we have established that targeting SYK reduces viability and promotes differentiation in AML, little is known about the downstream signaling effectors of SYK in AML. There is definitely a significant body of materials documenting the part of SYK in non-Hodgkins lymphoma, which offers served as a useful construction for checking out SYK in AML.8, 9, 11, 13C16 In B-cell lymphoma, SYK has been demonstrated to be a critical regulator of mTOR activity.14, Agnuside manufacture 17 mTOR positively ...
Fingerprint Dive into the research topics of Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages. Together they form a unique fingerprint. ...
Based on genetic studies that establish the role of spleen tyrosine kinase (Syk) in immune function, inhibitors of this kinase are being investigated as therapeutic agents for inflammatory diseases. Because genetic studies eliminate both adapter functions and kinase activity of Syk, it is difficult to delineate the effect of kinase inhibition alone as would be the goal with small-molecule kinase inhibitors. We tested the hypothesis that specific pharmacological inhibition of Syk activity retains the immunomodulatory potential of Syk genetic deficiency. We report here on the discovery of (4-(3-(2H-1,2,3-triazol-2-yl)phenylamino)-2-((1R,2S)-2-aminocyclohexylamino) pyrimidine-5-carboxamide acetate (P505-15), a highly specific and potent inhibitor of purified Syk (IC50 1-2 nM). In human whole blood, P505-15 potently inhibited B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 μM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 μM). ...
TY - JOUR. T1 - Inhibition of T Cell Receptor-mediated Signal Transduction by Erbstatin. AU - Imoto, Masaya. AU - Nakamura, Takeshi. AU - Tanaka, Shin Ichiro. AU - Umezawa, Kazuo. PY - 1994. Y1 - 1994. N2 - Erbstatin, a tyrosine kinase inhibitor, inhibited p59fyn- and p56lck-kinases in vitrowith IC50s of 0.21 and 0.18μg/ml, respectively. Inositol phosphates formation, enhanced by anti-CD3, was also inhibited by erbstatin. Moreover, erbstatin treatment prevented anti-CD3-induced interleukin 2 (IL-2) production, but phorbol ester-induced IL-2 production was not affected by erbstatin.. AB - Erbstatin, a tyrosine kinase inhibitor, inhibited p59fyn- and p56lck-kinases in vitrowith IC50s of 0.21 and 0.18μg/ml, respectively. Inositol phosphates formation, enhanced by anti-CD3, was also inhibited by erbstatin. Moreover, erbstatin treatment prevented anti-CD3-induced interleukin 2 (IL-2) production, but phorbol ester-induced IL-2 production was not affected by erbstatin.. UR - ...
Brutons tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor activity, first in animal models and subsequently in clinical studies. In particular, the orally administered irreversible BTK inhibitor ibrutinib is associated with high response rates in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle-cell lymphoma (MCL), including patients with high-risk genetic lesions. Because ibrutinib is generally well tolerated and shows durable ...
Breast Tumor Kinase (Brk/PTK6) has a relatively limited expression profile in normal tissue. Its expression is restricted to epithelial cells that are differentiating such as those in the epidermis, and Brk expression appears to be absent from proliferating cells in normal tissue. Also, there is now some evidence to suggest that Brk plays a functional role in the differentiation of the keratinocytes in the epidermis. We have, therefore, investigated the role that Brk/PTK6 plays in normal human primary keratinocytes by suppressing protein levels using RNA interference. We show that as primary human keratinocytes are induced to differentiate in vitro, Brk levels decrease. Decreasing Brk protein levels lead to an increase in the number of cells with a permeable plasma membrane, a decrease in epidermal growth factor receptor (EGFR) and a parallel increase in keratin 10 levels, but classical markers of apoptosis or terminal differentiation are not affected. We propose Brk, Keratin 10 and EGFR are ...
Purpose : The association between uveal melanoma (UM) and ultraviolet light (UV) damage has yet to be conclusively demonstrated. Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase with anti-tumorigenic properties, has been shown to be upregulated under stressed conditions, such as following UV exposure. In the present study, we used Syk as a UV exposure marker and compared its expression in the conjunctiva and choroid of normal human eyes (NHE) and eyes containing UM to investigate the link between UV damage and UM. We also investigated basal Syk levels in conjunctival fibroblasts to assess their sensitivity to UV damage. Methods : Automated immunohistochemical staining against Syk was performed in 23 UM enucleated eyes and 34 NHE age-matched Eyebank eyes. A score was established by evaluating staining intensity (0-2) and extension (0-2); both values were added to generate an immunoreactive score (IRS; 0-4). Syk expression was evaluated in choroidal fibroblasts in all eyes. In order to ...
Protein-tyrosine kinase C-terminal Src kinase (Csk) was originally purified as a kinase for phosphorylating Src and other Src family kinases. The phosphorylation of a C-terminal tyrosine residue of Src family kinases suppresses their kinase activity. Therefore, most physiological studies regarding Csk function have been focused on Csk as a negative regulator of Src family tyrosine kinases and as a potential tumor suppressor. Paradoxically, the protein levels of Csk were elevated in some human carcinomas. In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus ...
TY - JOUR. T1 - Differential regulation of protein tyrosine kinase on free radical production, granule enzyme release, and cytokine synthesis by activated murine peritoneal macrophages. AU - Kim, Young Ki. AU - Jang, Yoon Young. AU - Kim, Dong Hyun. AU - Ko, Hyun Hee. AU - Han, Eun Sook. AU - Lee, Chung Soo. PY - 2001/1/1. Y1 - 2001/1/1. N2 - The present study examined the regulatory effect of tyrosine kinase inhibitors (genistein, tyrphostin, and 2, 5-dihydroxycinnamate) on the free radical production, granule enzyme release, and synthesis of interleukin (IL)-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) in murine peritoneal macrophages exposed to different stimulators [10 ng/mL of IL-1, 1 μg/mL of lipopolysaccharide (LPS), and 1 μM N-formyl-methionyl-leucyl-phenylalanine (fMLP)]. Protein tyrosine kinase (PTK) inhibitors attenuated the stimulated superoxide, hydrogen peroxide, and nitric oxide production in macrophages stimulated with IL-1, LPS, or fMLP N, ...
Soluble extracts prepared from bovine thymus contain an angiotensin-I-phosphorylating activity that is activated several-fold by high concentrations of NaCl. Fractionation of this protein-tyrosine kinase activity by chromatography on DEAE-cellulose yields a major diffuse peak of activity. The enzymes responsible for this activity are found at much higher levels in extracts from bovine thymus than from bovine spleen. The peak of activity from the DEAE-cellulose column can be further separated into two major peaks by chromatography on heparin-agarose. The second peak to elute from the heparin-agarose column was previously purified through several chromatographic steps to yield a 40 kDa protein-tyrosine kinase (p40). We have now partially purified the early-eluting peak of kinase activity by chromatography on columns of butyl-agarose, protamine-agarose and Sephacryl S200. The enzyme was identified following covalent modification with 5′-fluorosulphonylbenzoyladenosine (FSBA) by reactivity with ...
Wnts are secreted ligands that activate several receptor-mediated signal transduction cascades. Homeostatic Wnt signaling through β-catenin is required in adults, because either elevation or attenuation of β-catenin function has been linked to diverse diseases. To contribute to the identification of both protein and pharmacological regulators of this pathway, we describe a combinatorial screen that merged data from a high-throughput screen of known bioactive compounds with an independent focused small interfering RNA screen. Each screen independently revealed Brutons tyrosine kinase (BTK) as an inhibitor of Wnt-β-catenin signaling. Loss of BTK function in human colorectal cancer cells, human B cells, zebrafish embryos, and cells derived from X-linked agammaglobulinemia patients with a mutant BTK gene resulted in elevated Wnt-β-catenin signaling, confirming that BTK acts as a negative regulator of this pathway. From affinity purification-mass spectrometry and biochemical binding studies, we ...
Toll-like receptors play a key role in the signaling pathways of innate immune response and have been recently shown to contribute to vascular inflammation and atherosclerosis. Oxidation of LDL is considered a leading mechanism of atherogenesis, and in our previous studies, we demonstrated that minimally modified LDL (mmLDL) induced TLR4-dependent chemokine secretion as well as robust actin polymerization and spreading of macrophages. We noticed that these mmLDL-induced cytoskeletal rearrangements led to extensive vacuolization, characteristic of macropinocytosis. In this study, we examined the mechanisms of TLR4-induced actin polymerization and macropinocytosis. It has been reported that spleen tyrosine kinase (Syk) regulates actin cytoskeleton and that it may interact with TLR4. We found in the immunoprecipitation experiments that mmLDL induced Syk association with TLR4 as well as Syk phosphorylation. Next we developed a J774 macrophage cell line, which stably expressed Syk shRNA and had the ...
BTK is a cytoplasmic protein-tyrosine kinase, whose corresponding gene was isolated in the early 1990s. BTK was initially identified by positional cloning of the gene causing X-linked agammaglobulinemia ...
报告题目:Tuning T cell responses.. 报告人:Dr. Avery August. Professor and Chair. Department of Microbiology and Immunology. College of Veterinary Medicine, Cornell University. 时间:2017年9月20日(星期三)上午10:00. 地点:生化楼3层中厅. 主持人:吴聪颖研究员. 报告简介:. The August laboratory is interested in signals that regulate the choices that immune cells make in deciding to respond in an inflammatory or suppressive manner. We study these signals in the context of allergy and lung inflammation, using mouse genetic models and human cells. Specifically, we study a family of tyrosine kinases expressed by immune cells, the Tec family kinases, that regulate immune cell activation. Although these kinases are expressed in different immune cells such as T and B cells, and mast cells, their response to extracellular stimuli are different. Using mouse genetic models, we have found that the major Tec kinase expressed in T cells, Itk, positively regulates ...
Dendritic cells (DCs) are the only APCs capable of initiating adaptive immune responses. The initiation of immune responses requires that DCs 1) internalize
Supplementary MaterialsSupplementary figures. appearance. valuevaluevalueand in H-CAFs. (D) Recombinant IL-6, HGF or IL-8 was added to treat HCC cells having a dose dependent manner. Indicated antibodies were used to detect Rabbit Polyclonal to SSXT the protein level E-cadherin or Slug. (E) Left panel, the corresponding neutralizing antibodies were added to medium after HCC cells were treated with CAF-CM. Right panel, HCC cells were treated with recombinant IL-6, HGF or IL-8. Indicated antibodies were used to test the signals E-cadherin, Fibronectin, Slug, pSTAT3-S727 and STAT3. (F and G) Representative images and analysis show the IL-6 significantly induced Huh7 cells invasion subgroup than in the H-CAFssubgroup. Consistently, E-cadherin IHC score in H-CAFssubgroup was higher than H-CAFssubset (treatment than H-CAFstreatment, indicating that the secretions, especially cytokines could enhance the cell migration (Number S2B). Collectively, these data suggested the function of the signaling of ...
Dive into the research topics of Functional specificity of cytoplasmic and transmembrane tyrosine kinases: Identification of 130- and 75-kilodalton substrates of c-fps/fes tyrosine kinase in macrophages. Together they form a unique fingerprint. ...
To understand the basis for the γδ T cell-dependent hyper-IgE syndrome that develops in the absence of Itk, we performed a detailed analysis γδ NKT cells in Itk−/− mice. Our previous studies demonstrated that this γδ T cell subset, expressing the Vγ1.1/Vδ6.3 (V6) TCR and the transcription factor PLZF, was highly expanded in Itk−/− mice and could secrete large amounts of type II cytokines, such as IL-4 and IL-13 (15). Using a combination of phenotypic, functional, and molecular analysis of V6 cells in the thymus, spleen, and liver, we have determined a number of important features of these cells. First, we show that the increased V6 population in Itk−/− mice is generally accounted for by cells expressing high levels of PLZF and constitutively expressing IL-4 mRNA. Second, based on a comparison with iNKT cells, we conclude that Itk−/− V6 cells do not fully mature and cannot transit to the stage associated with high level IFN-γ production. Third, we provide evidence that ...
The non-receptor tyrosine kinase Src, which initiates podosome formation and regulates podosome structure, is a member of a family of nine closely related tyrosine kinases that is defined by a common domain structure, including a myristoylated N-terminal domain that targets Src to membranes, two Src-homology-protein-binding domains (SH2 and SH3) and the tyrosine-kinase catalytic domain. Activation of Src occurs either when Tyr527 is dephosphorylated, allowing the `opening of the molecule, or when the intramolecular interactions of the SH2 or SH3 domains are disrupted by intermolecular interactions with other Src-binding partners. Activation of Src leads to the autophosphorylation of Tyr416 in the activation loop of the kinase domain, which is essential for the full tyrosine-kinase activity of Src (Roskoski, 2004).. As mentioned previously, expression of v-Src, the oncogenic and constitutively active form of Src, induces a rearrangement of the actin cytoskeleton that is characterized by a switch ...
Top performende anti-Schwein Spleen tyrosine Kinase Antikörper für Immunohistochemistry (Paraffin-embedded Sections) (IHC (p)) vergleichen & kaufen.
Tyrosine kinase (TK) inhibitors genistein and tyrphostin A23 (A23) inhibited Ca2+ currents in guinea-pig ventricular myocytes investigated under regular whole-cell circumstances (K+-free of charge Tyrodes superfusate; EGTA-buffered (pCaC10. (e.g., Body 5d). Raf265 derivative In six tests, the existing induced by 100 ?0.510.07 pA pF?1 in the lack of Ni2+ (Body 5b)). Open up in another window Body 5 Ramifications of A23, genistein, and Ni2+ on membrane currents in myocytes superfused with Ca2+-free of charge alternative and dialysed with pCa 7 alternative. The myocytes had been pulsed from ?40 mV to various other voltages HDAC10 for 200 ms at 0.2 Hz before, 5 min after application of 100 romantic relationship of A23-induced current under near-physiological ionic circumstances, myocytes had been dialysed using a 7 mM Na+ pipette solution and superfused with K+-free of charge Tyrodes solution that was supplemented with 10 A23 focus is proven in Body 7, as well as the Hill equation fitting the info ...
Tyrosine Protein Kinase Receptor UFO (AXL Oncogene or AXL or EC - Pipeline Review, H2 2017 Tyrosine Protein Kinase Receptor UFO (AXL Oncogene or - Market research report and industry analysis - 11296598
The growth, differentiation and functions of immune and hematopoietic cells are controlled by multiple cytokines, including interleukins (ILs) and colony stimulating factors (CSFs). Cytokines exert their biological effects through binding to cell‐surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases (JAKs). Cytokine‐induced receptor dimerization leads to the activation of JAKs, rapid tyrosine phosphorylation of the cytoplasmic domains and subsequent recruitment of various signaling proteins to the receptor complex (Ihle, 1995). Among these proteins are members of the signal transduction and activators of transcription (STAT) family (Ihle, 1996; Darnell, 1997; OShea, 1997). The tyrosine‐phosphorylated STATs form homo‐ or heterodimers and translocate into the nucleus, they then activate target genes.. The regulation of the JAKs is a central component in the regulation of cytokine signaling. Because of the critical role of ...
Preclinical Research and Exploratory Development [D. B. M., A. D. L., X. X., S. G. L., J. G. C., G. L., R. E. S., T. J. A., T. J. N., L. B. L., L. J. M., J. C., E. C., K. G. M., J. M. C.], Biometabolism and Pharmacokinetics [J. Ö. H., J. S.], Discovery Technology [R. A. B.], and Chemistry [L. S., C. T., T. M., S. S., G. M.], SUGEN, Inc., South San Francisco, California ...
Protein-tyrosine kinases (PTKs) catalyze the transfer of the γ-phosphate of ATP to tyrosine residues of protein substrates, are critical components of signaling pathways that control cellular proliferation and differentiation. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs.. The RTK family includes the receptors for insulin and for many growth factors, such as EGF, FGF, PDGF, VEGF, and NGF. RTKs are transmembrane glycoproteins that are activated by the binding of their ligands, and they transduce the extracellular signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves (autophosphorylation) and on downstream signaling proteins. RTKs activate numerous signaling pathways within cells, leading to cell proliferation, differentiation, migration, or metabolic changes. In addition, nonreceptor tyrosine kinases (NRTKs), which include Src, JAKs, and Abl, among others, are integral components of the signaling cascades ...
Targeted inhibition of Bruton tyrosine kinase (BTK) with the irreversible inhibitor ibrutinib has improved outcomes for patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL). Here, we describe preclinical investigations of ARQ 531, a potent, reversible inhibitor of BTK with additional activity against Src family kinases and kinases related to ERK signaling. We hypothesized that targeting additional kinases would improve global inhibition of signaling pathways, producing more robust responses. In vitro treatment of patient CLL cells with ARQ 531 decreases BTK-mediated functions including B-cell receptor (BCR) signaling, viability, migration, CD40 and CD86 expression, and NF-κB gene transcription. In vivo, ARQ 531 was found to increase survival over ibrutinib in a murine Eμ-TCL1 engraftment model of CLL and a murine Eμ-MYC/TCL1 engraftment model resembling Richter transformation. Additionally, ARQ 531 inhibits CLL cell survival and suppresses BCR-mediated ...
Cancer is a leading cause of death in California. Many cancers resist current therapies due to therapy-resistant cancer stem cells (CSCs). A team at UCSD is testing an antibody therapy called cirmtuzumab in a clinical trial study to treat a blood cancer, Chronic Lymphocytic Leukemia (CLL). The antibody recognizes and attaches to a protein on the surface of cancer stem cells. This attachment disables the protein which slows the growth of the leukemia and makes it more vulnerable to anti-cancer drugs.
There is an unmet need for new medicines for the treatment of cardiovascular disease, especially drugs that target macrophage inflammation in atherosclerosis. One potential source of new anti-inflammatory drugs is repurposing medicines currently used in oncology. Ibrutinib (imbruvica) is a low molecular weight non-competitive inhibitor of Brutons tyrosine kinase (BTK) kinase activity that is used in the treatment of leukaemia. Gareth Purvis has shown that ibrutinib has tissue protective effects in pre-clinical models of type-2 diabetes. Work in the Greaves Lab has shown ibrutinib reduces macrophage NF-KB and inflammasome activation and hence reduces inflammatory cytokine production. In addition we have shown that oral delivery of ibrutinib inhibits inflammatory cell recruitment in a murine models of acute inflammation. We will publish our novel findings and then use that paper to apply for new funding streams to take BTK inhibitors into translational studies for diseases characterised by ...
Data Availability StatementAll relevant data are within the paper. Compact disc4 T Ximelagatran cells, but abrogated Foxp3 expression induced by ITK knockdown conversely. Our data claim that concentrating on ITK in individual T cells could be an effective method of increase TREG in the framework of PPP1R12A autoimmune illnesses, but concomitant inhibition of various other Tec family kinases might negate this effect. Launch Interleukin-2-inducible T-cell kinase (ITK) is normally a member from the Tec kinase category of non-receptor tyrosine kinases and mediates T cell signaling downstream of TCR activation [1]. Signaling through ITK modulates T cell activation, T helper cell differentiation, and thymic collection of developing thymocytes. ITK continues to be implicated as a crucial node in T NK and cell cell mediated irritation, leading to curiosity about developing therapeutics to modulate ITK function in inflammatory and autoimmune illnesses [2, 3]. ITK is normally thought to get Th2-mediated ...
Fingerprint Dive into the research topics of Ly-6A is required for T cell receptor expression and protein tyrosine kinase fyn activity. Together they form a unique fingerprint. ...
The TLRs play a key role in host defense against infection and injury, and mounting evidence suggests that these receptors may also play a role in diseases such autoimmunity, atherosclerosis, and cancer. Activation of TLRs on macrophages results in the production of multiple soluble mediators including the key inflammatory cytokines, TNF and IL-6. Thus, the intracellular signaling mechanism by which TLRs signal is a subject of great interest. As well as activating the NF-κB and MAPK pathways, TLR engagement leads to tyrosine kinase activation within minutes. Src family kinases (SFKs) are the largest nonreceptor tyrosine kinase family with nine members: Src, Hck, Lyn, Fyn, Fgr, Blk, Lck, Yes, and Ylk. The role of the SFKs in TLR signaling has been an area of much controversy, with conflicting findings between studies using chemical inhibitors and knockout mice. Using primary human macrophages in combination with adenoviral overexpression and small interfering RNA knockdown studies, we show that the SFK,
Fingerprint Dive into the research topics of Expression of lineage-restricted protein tyrosine kinase genes in human natural killer cells. Together they form a unique fingerprint. ...
Src (proto-oncogene tyrosine-protein kinase) family is a family of non-receptor tyrosine kinases including nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. In immune cells, Src-family kinases (SFKs) have been implicated as critical regulators of a large number of intracellular signaling pathways. Src-family kinases (SFKs) occupy a proximal position in numerous signaling transduction cascades including those emanating from the T and B cell antigen receptors, Fc receptors, growth factor receptors, cytokine receptors, and integrins.
The Receptor Tyrosine Kinase (RTK) Met influences behaviour of several cancers by controlling growth, survival and metastasis. Recently, compartmentalisation of signals generated by RTKs, due to their endocytosis / trafficking, has emerged as a major determinant of various cell functions. The aim of my project was to study oncogenic Met signalling in relation to endosomal trafficking and to determine the consequences of such spatial changes on tumour cell growth and migration in vitro and in vivo. The model studied was NIH3T3 cells stably transfected with Wild type (Wt) Met or with three distinct mutants reported in human cancers. I found that two activating mutations in the kinase domain are highly tumorigenic in vivo. Using functional assays and tumour growth experiments, I demonstrated that one mutant is highly sensitive to Met specific tyrosine kinase inhibitors (TKI) while another is resistant. Such results suggested that therapeutical approaches to these mutants should be different. ...
"The Fes protein-tyrosine kinase phosphorylates a subset of macrophage proteins that are involved in cell adhesion and cell-cell ... "Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS". Molecular and ... Tyrosine-protein kinase Fes/Fps also known as proto-oncogene c-Fes/Fps is an enzyme that in humans is encoded by the FES gene. ... Overview of all the structural information available in the PDB for UniProt: P07332 (Tyrosine-protein kinase Fes/Fps) at the ...
Tyrosine-protein kinase 6 is an enzyme that in humans is encoded by the PTK6 gene. Tyrosine-protein kinase 6-also known as BRK ... "PTK6 protein tyrosine kinase 6". National Center for Biotechnology Information (NCBI). 4 June 2020. Mitchell, P J; Sara E A; ... Lee ST, Strunk KM, Spritz RA (December 1993). "A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes ... Koo BK, Kim MH, Lee ST, Lee W (2002). "Purification and spectroscopic characterization of the human protein tyrosine kinase-6 ...
... in tyrosine-protein kinase receptors; and in the programmed cell death protein 1 (PD1). Immunoglobulin V-set, subgroup InterPro ... V-set domains are found in diverse protein families, including immunoglobulin light and heavy chains; in several T-cell ...
Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain ... Histidine-specific protein kinases are structurally distinct from other protein kinases and are found in prokaryotes, fungi, ... cAMP-dependent pathway: In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase) (see picture ... most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response. Proteins ...
Experimental medications: sorafenib a combined Tyrosine protein kinases inhibitor. Scheduling of drug treatments and ... kinases. Heparanase cleaves heparin sulfate chains of HSPGs, which have an extensive network with several proteins on the cell ... increased tyrosine phosphorylytion of the focal adhesion kinase, and activation and nuclear translocation of mitogen-activated ... and causes activation of the signaling tyrosine kinase receptors even under low circulating concentrations of growth factors. ...
Non-receptor tyrosine-protein kinase TYK2. Protein-tyrosine phosphatases PTPN3 and PTPN4, enzymes that appear to act at ... Focal-adhesion kinases (FAKs), cytoplasmic protein tyrosine kinases involved in signalling through integrins. Janus tyrosine ... Protein-tyrosine phosphatases PTPN14 and PTP-D1, PTP-RL10 and PTP2E. Caenorhabditis elegans protein phosphatase ptp-1. Chishti ... Ezrin, moesin, and radixin are highly related proteins (ERM protein family), but the other proteins in which the FERM domain is ...
The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to ... c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is ... Furge KA, Zhang YW, Vande Woude GF (November 2000). "Met receptor tyrosine kinase: enhanced signaling through adapter proteins ... which is then translated into a 1,390 amino-acid MET protein. MET is a receptor tyrosine kinase (RTK) that is produced as a ...
The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually ... Signal transducing adaptor proteins CDC24 Cdc25 PI3 kinase Phospholipase Ras GTPase-activating protein Vav proto-oncogene GRB2 ... It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and ... SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and ...
2002). "Regulation of tyrosine hydroxylase by stress-activated protein kinases". J. Neurochem. 83 (4): 775-83. doi:10.1046/j. ... Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with ... and stress-activated protein kinase-1 in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires both ... 2001). "Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3 ...
Receptor tyrosine-protein kinase erbB-3, also known as HER3 (human epidermal growth factor receptor 3), is a membrane bound ... Roskoski R (2014). "The ErbB/HER family of protein-tyrosine kinases and cancer". Pharmacol. Res. 79: 34-74. doi:10.1016/j.phrs. ... ErbB3 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. The kinase-impaired ... "Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3". Nature. 445 (7126): 437-41. doi:10.1038/ ...
Requirement for p56 LCK and ZAP-70 protein tyrosine kinases". European Journal of Biochemistry. 268 (5): 1508-15. doi:10.1046/j ... Upon ligation of the T-cell receptor, protein kinase Lck is recruited and phosphorylates the ITAMs of the CD3 cytoplasmic tail ... All proteins of the NF-κB family share a Rel homology domain in their N-terminus. A subfamily of NF-κB proteins, including RelA ... S2CID 35240781.; (g) Basu S, Rosenzweig KR, Youmell M, Price BD (June 1998). "The DNA-dependent protein kinase participates in ...
Roskoski R (September 2014). "ErbB/HER protein-tyrosine kinases: Structures and small molecule inhibitors". Pharmacological ...
The Bacterial protein tyrosine-kinase database (BYKdb) is a specialized database of computer-annotated bacterial tyrosine- ... the Bacterial protein tYrosine Kinase database". Nucleic Acids Res. England. 40 (Database issue): D321-4. doi:10.1093/nar/ ... kinases that share no resemblance with their eukaryotic counterparts. Tyrosine-kinases Jadeau, Fanny; Grangeasse Christophe; ...
Tyrosine-protein kinase receptor TYRO3 is an enzyme that in humans is encoded by the TYRO3 gene. TYRO3 has been shown to ... Crosier PS, Freeman SA, Orlic D, Bodine DM, Crosier KE (1996). "The Dtk receptor tyrosine kinase, which binds protein S, is ... "Entrez Gene: TYRO3 TYRO3 protein tyrosine kinase". Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (April 1996). " ... "The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases". Int. J. Biochem. Cell Biol. 37 (11): 2344 ...
They signal through receptor tyrosine kinases and serine/threonine protein kinases. Several other biomolecules that have ... Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinase. In ... Whereas neurotrophic factors within the neurotrophin family commonly have a protein tyrosine kinase receptor (Trk), ... Later studies determined GDNF uses a receptor tyrosine kinase and a high-affinity ligand-binding co-receptor GFRα. GDNF has an ...
Tyrosine-protein kinase-like 7 also known as colon carcinoma kinase 4 (CCK4) is a receptor tyrosine kinase that in humans is ... Receptor protein tyrosine kinases transduce extracellular signals across the cell membrane. A subgroup of these kinases lack ... The protein encoded by this gene an intracellular domain with tyrosine kinase homology and may function as a cell adhesion ... Banga SS, Ozer HL, Park SK, Lee ST (1997). "Assignment of PTK7 encoding a receptor protein tyrosine kinase-like molecule to ...
"Protein tyrosine phosphatase epsilon inhibits signaling by mitogen-activated protein kinases". Mol. Cancer Res. 1 (7): 541-50. ... The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling ... "Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase ... "Entrez Gene: PTPRE protein tyrosine phosphatase, receptor type, E". Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A ...
Barbacid M, Lamballe F, Pulido D, Klein R (December 1991). "The trk family of tyrosine protein kinase receptors". Biochimica et ... stands for tropomyosin receptor kinase or tyrosine receptor kinase (and not "tyrosine kinase receptor" nor "tropomyosin-related ... The three known pathways are PLC, Ras/MAPK (mitogen-activated protein kinase) and the PI3K (phosphatidylinositol 3-kinase) ... "A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences". Nature. 319 (6056): 743- ...
... protein or FLT3 protein. This protein is a member of the class III family of receptor tyrosine kinases; PDGFRA, PDGFRB, c-KIT ... The JAK2 gene encodes a member of the Janus kinase family of non-receptor tyrosine kinase, JAK2. The JAK2 protein associates ... With the discovery of the uncontrolled tyrosine kinase activity of this disorder and the use of tyrosine kinase inhibitors. ... BCR encodes the breakpoint cluster region protein. This protein possess Serine/threonine-specific protein kinase activity and ...
Proto-oncogene tyrosine-protein kinase Yes is a non-receptor tyrosine kinase that in humans is encoded by the YES1 gene. This ... The encoded protein has tyrosine kinase activity and belongs to the src family. This gene lies in close proximity to ... Non-receptor type protein-tyrosine kinases closely related to src and yes compose a multigene family". Int. Symp. Princess ... Overview of all the structural information available in the PDB for UniProt: P07947 (Tyrosine-protein kinase Yes) at the PDBe- ...
These proteins activate protein tyrosine kinase (PTK) that phosphorylates various proteins important for capacitation and ... Then, it converts adenosine triphosphate into cyclic AMP, which activates Protein kinase A. PKA leads to protein tyrosine ... Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase) regulates gene transcription through successive kinase ... So, ZP3 can activate G protein coupled receptors and tyrosine kinase receptors, that leads to production of PLC. PLC cleaves ...
... is an ATP-competitive protein tyrosine kinase inhibitor. The main targets of dasatinib are BCR/Abl (the "Philadelphia ... It is a tyrosine-kinase inhibitor and works by blocking a number of tyrosine kinases such as Bcr-Abl and the Src kinase family ... and several other tyrosine kinases. Strong inhibition of the activated BCR-ABL kinase distinguishes dasatinib from other CML ... Dasatinib has been shown to induce apoptosis in senescent cells by inhibiting Src kinase, whereas quercetin inhibits the anti- ...
Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene. ... Cao C, Leng Y, Li C, Kufe D (April 2003). "Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the ... ABL2 is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The similarity of the proteins ... Wang B, Kruh GD (1996). "Subcellular localization of the Arg protein tyrosine kinase". Oncogene. 13 (1): 193-7. PMID 8700546. ...
By looking at three major types of receptors, (G protein coupled receptors, receptor tyrosine kinases, and ion channel ... Many of the relay molecules in a signal transduction pathway are protein kinases and often act on other protein kinases in the ... Many of the relay molecules in a signal transduction pathway are protein kinases and often act on other protein kinases in the ... Many of the relay molecules in a signal transduction pathway are protein kinases and often act on other protein kinases in the ...
"Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases". Proc. ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134 ... Méthot N, Rom E, Olsen H, Sonenberg N (January 1997). "The human homologue of the yeast Prt1 protein is an integral part of the ... Morris-Desbois C, Réty S, Ferro M, Garin J, Jalinot P (December 2001). "The human protein HSPC021 interacts with Int-6 and is ...
Protein kinase inhibitor McCormick F, Fabbro D (2005). Protein Tyrosine Kinases: From Inhibitors to Useful Drugs (Cancer Drug ... Mubritinib (TAK-165) is a protein kinase inhibitor which was under development by Takeda for the treatment of cancer. It ...
"Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. ... Mitotic spindle assembly checkpoint protein MAD2A is a protein that in humans is encoded by the MAD2L1 gene. MAD2L1 is a ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038/ ... Liu YC, Pan J, Zhang C, Fan W, Collinge M, Bender JR, Weissman SM (April 1999). "A MHC-encoded ubiquitin-like protein (FAT10) ...
"Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases". Nature. 343 (6256): 377-81 ... Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I, Avraham S, Avraham H (2000). "RAFTK/Pyk2 tyrosine kinase ... Shiota M, Tanihiro T, Nakagawa Y, Aoki N, Ishida N, Miyazaki K, Ullrich A, Miyazaki H (2003). "Protein tyrosine phosphatase ... Rho GTPase-activating protein 5 is an enzyme that in humans is encoded by the ARHGAP5 gene. Rho GTPase activating protein 5 ...
"Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". The Journal ... by protein-tyrosine phosphatase PTPH1". The Journal of Biological Chemistry. 277 (45): 42463-70. doi:10.1074/jbc.M207459200. ... ADAM17 also regulates the MAP kinase signaling pathway by regulating shedding of the EGFR ligand amphiregulin in the mammary ... Díaz-Rodríguez E, Montero JC, Esparís-Ogando A, Yuste L, Pandiella A (June 2002). "Extracellular signal-regulated kinase ...
Proteins known to contain a Btk-type zinc finger include: Mammalian Bruton's tyrosine kinase (Btk), a protein tyrosine kinase ... Mammalian Tec, Bmx, and Itk proteins, which are tyrosine protein kinases of the Tec subfamily. Drosophila tyrosine-protein ... Btk is a member of the Tec family of protein tyrosine kinases (PTK). These kinases contain a conserved Tec homology (TH) domain ... "The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain". Nature. 395 (6704 ...
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ... The CD20 proteins are sticking out of the cell membrane, and rituximab, the Y-shaped antibody, is binding to the CD20 proteins. ... The antibody binds to the cell surface protein CD20. CD20 is widely expressed on B cells, from early pre-B cells to later in ... In contrast, when the B cell lacked this asymmetric protein cluster, it was killed only 40% of the time.[36][37] ...
... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth ... Minkovsky N, Berezov A (December 2008). "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors ... It belongs to the tyrosine kinase inhibitor family of medications.[4] It is taken by mouth.[4] ...
Vallenius T، Mäkelä TP (2003). "Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein.". J. Cell ... Brill LM، Salomon AR، Ficarro SB، Mukherji M، Stettler-Gill M، Peters EC (2004). "Robust phosphoproteomic profiling of tyrosine ... "Towards a proteome-scale map of the human protein-protein interaction network.". Nature. 437 (7062): 1173-8. PMID 16189514. doi ... Wang H، Harrison-Shostak DC، Lemasters JJ، Herman B (1996). "Cloning of a rat cDNA encoding a novel LIM domain protein with ...
... mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 phosphorylates cellular proteins (including histone H3 ... Tyrosine phosphatase. *PTEN *Bannayan-Riley-Ruvalcaba syndrome. *Lhermitte-Duclos disease. *Cowden syndrome ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ... The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3 ...
Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ... Fig 2. Schematic diagram of a GABAA receptor protein ((α1)2(β2)2(γ2)) which illustrates the five combined subunits that form ... The synaptic anchoring protein Gephyrin is indirectly linked to the GABAA receptors. ... molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system. ...
... binding to cAMP-dependent protein kinase (PKA).[111] Moclobemide is chemically unrelated to irreversible MAOI antidepressants ... Substrates→Products: Phenylalanine→Tyrosine. *Inhibitors: 3,4-Dihydroxystyrene. TH. *Substrates→Products: Tyrosine→L-DOPA ( ... The elimination half-life is around 2 hours.[8][118] It is moderately bound to plasma proteins, especially albumin.[8] However ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ... The active site is a region on an enzyme which a particular protein or substrate can bind to. The active site will only allow ... "Functional Design of Proteins". Molecular Cell Biology. 4th edition. W. H. Freeman. ...
"Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired ... Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies. (1) Basic domains. 1.2. *Feingold ...
1992). "The lymphocyte-specific tyrosine protein kinase p56lck is endocytosed in Jurkat cells stimulated via CD2.". J. Immunol. ... to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation pathways dependent on protein kinase C and ... Wilkins A, Yang W, Yang J (2003). "Structural biology of the cell adhesion protein CD2: from molecular recognition to protein ... 1990). "Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV.". Folia Biol. (Praha) ...
... who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, ... Serine/threonine/tyrosine phosphorylation[edit]. Addition of a negatively charged phosphate group can lead to major changes in ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... Nuclear protein Ataxia-Telangiectasia (NPAT), also known as nuclear protein coactivator of histone transcription, is a ...
Type 3: Kinase-linked and related receptors (see "Receptor tyrosine kinase" and "Enzyme-linked receptor") - They are composed ... Ligands connect to specific receptor proteins based on the shape of the active site of the protein. ... and can be a protein or peptide (short protein), or another small molecule such as a neurotransmitter, hormone, pharmaceutical ... In biochemistry and pharmacology, a receptor is a protein molecule that receives chemical signals from outside a cell.[1] When ...
positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... Iwasaki Y, Gay B, Wada K, Koizumi S (July 1998). "Association of the Src family tyrosine kinase Fyn with TrkB". Journal of ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000176697 - Ensembl, May ...
EGFR-specific tyrosine kinase inhibitors such as gefitinib have shown limited therapeutic success. This resistance is proposed ... the Wnt signaling pathway leads to stabilization of β-catenin through inactivation of a protein complex containing the tumor ... HER2 kinase inhibitors, such as lapatinib, have also demonstrated clinical efficacy in HER2 overexpressing breast cancers by ... For example, one group found a positive correlation between persistently activated tyrosine-phosphorylated STAT3 (pSTAT3), ...
FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a ... Thakker DR, Standifer KM (2003). „Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation.". ... Nociceptinski receptor (NOP, orfaninski FQ receptor, kapa tip 3 opioidni receptor) je protein koji je kod čoveka kodiran OPRL1 ... signalni put G-protein spregnutog receptora. • G-proteinska signalizacija, inhibicioni put adenilat ciklaze. • elevacija ...
"Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3". ... CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker. ... Proteins: clusters of differentiation (see also list of human clusters of differentiation) ... "A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and ...
"Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase". J. Biol. Chem. 275 (34): ... "Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias". Oncogene ... Nash RA, Caldecott KW, Barnes DE, Lindahl T (April 1997). "XRCC1 protein interacts with one of two distinct forms of DNA ligase ... interaction between DNA polymerase beta and the XRCC1 protein". EMBO J. 15 (23): 6662-70. PMC 452490. PMID 8978692.. ...
2000). "The protein tyrosine kinase family of the human genome". Oncogene 19 (49): 5548-5557. PMID 11114734. doi:10.1038/sj.onc ... Signal provodeći adapterski protein: Gradivni protein. Drugi glasnik: cAMP-zavisni put • Ca2+ signalizacija • Lipidna ... Zwick, E. Bange, J. Ullrich, A. (2001). "Receptor tyrosine kinase signalling as a target for cancer intervention strategies". ... G protein-spregnuti receptor (Hedgehog, Wnt) • RTK (TGF beta, MAPK/ERK) • Notch • JAK-STAT • Akt/PKB • Fas apoptoza • Hippo • ...
The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of ... receptor tyrosine kinases". EMBO J. 15 (2): 290-298. doi:10.1002/j.1460-2075.1996.tb00359.x. PMC 449944. PMID 8617204.. ...
protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... tyrosine 3-monooxygenase) kinase (EC *STK4. Myosin-heavy-chain kinase (EC *Aurora kinase *Aurora A kinase ... The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ...
... and the Fyn protein-tyrosine kinase". Molecular Biology Reports. 26 (3): 173-7. doi:10.1023/A:1006954206151. PMID 10532312.. ... protein binding. • identical protein binding. • actin binding. • protein kinase binding. • small GTPase binding. • Rac GTPase ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ... "The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck". The Journal of Biological ...
positive regulation of protein tyrosine kinase activity. • positive regulation of protein targeting to membrane. • modulation ... negative regulation of protein processing. • protein destabilization. • activation of protein kinase activity. • calcium- ... ATP-dependent protein binding. • metal ion binding. • tubulin binding. • protein binding. • identical protein binding. • copper ... PRNP (prion protein) is the human gene encoding for the major prion protein PrP (proetase-resistant-protein, Pr for prion, and ...
protein tyrosine kinase binding. Cellular component. • cytoplasm. • cell junction. • cytoskeleton. • focal adhesion. • cell ... positive regulation of protein tyrosine kinase activity. • positive regulation of substrate adhesion-dependent cell spreading. ... "Entrez Gene: Cas scaffolding protein family member 4".. *^ a b Tikhmyanova N, Little JL, Golemis EA (April 2010). "CAS proteins ... Cas scaffolding protein family member 4 is a protein that in humans is encoded by the CASS4 gene.[5] ...
Copurification of tyrosine hydroxylase from rat pheochromocytoma by protein kinase". C. R. Acad. Sci. III. 302: 435-438. PMID ... Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley- ... Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins ( ... Branden C; Tooze J. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN 0-8153-2305-0.. ...
CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ... This allows cytoplasmic kinases of the Syk family (ZAP-70) to bind to the ITAM and activated ZAP-70 phosphorylates tyrosines on ... Zap70 - a Syk family kinase that binds to ITAM sequences upon tyrosine phosphorylation by Lck and Fyn, and phosphorylates LAT ... T cells utilise the Src family kinases in transmembrane signalling largely to phosphorylate tyrosines that are part of ...
cellular protein metabolic process. • insulin receptor signaling pathway. • positive regulation of protein kinase B signaling. ... positive regulation of peptidyl-tyrosine phosphorylation. • striated muscle cell differentiation. • regulation of muscle cell ... protein serine/threonine kinase activator activity. • receptor ligand activity. Cellular component. • extracellular region. • ... positive regulation of protein serine/threonine kinase activity. • carbohydrate metabolic process. • regulation of receptor ...
"Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C δ in a mouse ... 2acu: TYROSINE-48 IS THE PROTON DONOR AND HISTIDINE-110 DIRECTS SUBSTRATE STEREOCHEMICAL SELECTIVITY IN THE REDUCTION REACTION ... stress-activated protein kinase signaling cascade. • cellular response to peptide. • daunorubicin metabolic process. • ... Protein[edit]. AKR1B1 consists of 316 amino acid residues and weighs 35853Da. It does not possess the traditional dinucleotide ...
... it reduces neuron firing rate and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT ... It is possible to assemble phenethylamine structures for synthesis of compounds such as epinephrine, amphetamines, tyrosine and ...
In terms of intracellular signaling, GHB inhibits mitogen activated protein (MAP) kinase action via the GABAB receptor ... Tyrosine→Melanin. *Albinism: Ocular albinism (1). *Oculocutaneous albinism (Hermansky-Pudlak syndrome). *Waardenburg syndrome ... Ren, X.; Mody, I. (2003). "Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABAB receptor ... GABA acts via binding to its receptors which include the ligand gated ion channels, GABAA and GABAC and the G-protein couple ...
positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... Iwasaki Y, Gay B, Wada K, Koizumi S (July 1998). "Association of the Src family tyrosine kinase Fyn with TrkB". Journal of ... Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions ...
FMS-like tyrosine kinase 3 ligand (FLT3L). *Leukemia/leukocyte inhibitory factor (LIF) ... Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte.[1] They are protein ...
Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells ... Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Protein family membership. *Tyrosine-protein kinase, non-receptor Jak/Tyk2 (IPR016251)*Tyrosine-protein kinase, non-receptor ... 0004672 protein kinase activity GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine ...
Tyrosine-protein kinase BLK, also known as B lymphocyte kinase, is a non-receptor tyrosine kinase that in humans is encoded by ... It is of the Src family of tyrosine kinases. The tyrosine-protein kinase BLK has been shown to interact with UBE3A. ... BLK B lymphoid tyrosine kinase". Oda H, Kumar S, Howley PM (August 1999). "Regulation of the Src family tyrosine kinase Blk ... microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase". Mol. Cell. Biol. 13 (9): ...
Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene. SYK ... SYK Spleen tyrosine kinase". Chan AC, Iwashima M, Turck CW, Weiss A (November 1992). "ZAP-70: a 70 kd protein-tyrosine kinase ... along with Zap-70, is a member of the Syk family of tyrosine kinases. These non-receptor cytoplasmic tyrosine kinases share a ... Sada K, Minami Y, Yamamura H (September 1997). "Relocation of Syk protein-tyrosine kinase to the actin filament network and ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Protein tyrosine kinases Src and Csk: a tails tale.. Curr Opin Chem Biol 7 580-5 2003 ... CSK is a kinase that catalyzes phosphorylation of the tail tyrosine site in Src kinase. Similar to Src, it contains an SH2 ...
... and methods of using them to treat tyrosine kinase-dependent diseases and conditions in mammals: wherein n is an integer, ... regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, ... Protein tyrosine kinase inhibitors. US20090298855 *. Jul 28, 2009. Dec 3, 2009. Critical Outcome Technologies Inc.. Protein ... Tyrosine kinases can be categorized as receptor type or non-receptor type. Receptor type tyrosine kinases have an extracellular ...
A number of tyrosine kinase inhibitors that target c-Src tyrosine kinase (as well as related tyrosine kinases) have been ... c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ... Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase ...
... induces protein tyrosine phosphorylation, implicating one or more B-cell protein-tyrosine kinases (PTKs) in sIg signal ... Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases.. A L Burkhardt, M Brunswick, J ... Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. ... Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. ...
Interferon-induced nuclear signalling by Jak protein tyrosine kinases.. Silvennoinen O1, Ihle JN, Schlessinger J, Levy DE. ... Genetic complementation studies implicated the tyrosine kinase Tyk2 in IFN-alpha signalling and, more recently, the related ... Overexpression also activated endogenous Jak kinases, suggesting that interactions between Jak kinases are required during ... We now present biochemical evidence for Jak-family kinase involvement in IFN signal transduction. Jak1 was activated in ...
View protein in PROSITE. PS00107 PROTEIN_KINASE_ATP, 1 hit. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 ... View protein in PROSITE. PS00107 PROTEIN_KINASE_ATP, 1 hit. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 ... IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR001245 Ser-Thr/Tyr_kinase_cat_dom ... IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR001245 Ser-Thr/Tyr_kinase_cat_dom ...
... is a truncated form of the v-AbI Protein Tyrosine Kinase, a partner in the Gag-Abl fusion protein of the Abelson murine ... Abl Protein Tyrosine Kinase (AbI) is a truncated form of the v-AbI Protein Tyrosine Kinase, a partner in the Gag-Abl fusion ... 1X NEBuffer™ for Protein Kinases (PK) Incubate at 30°C 1X NEBuffer™ for Protein Kinases (PK) 50 mM Tris-HCl 10 mM MgCl2 0.1 mM ... The recognition motif for phosphorylation by Abl is I/V/LYXXP/F. Abl, like many cytosolic protein tyrosine kinases, ...
View protein in PROSITE. PS00107, PROTEIN_KINASE_ATP, 1 hit. PS50011, PROTEIN_KINASE_DOM, 1 hit. PS00109, PROTEIN_KINASE_ ... View protein in PROSITE. PS00107, PROTEIN_KINASE_ATP, 1 hit. PS50011, PROTEIN_KINASE_DOM, 1 hit. PS00109, PROTEIN_KINASE_ ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR000494, Rcpt_L-dom. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR000494, Rcpt_L-dom. ...
By modeling vandetanib and PTK6 complex, researchers at LSU found that the KRAS protein to also contain a similar drug-binding ... Chemotherapeutic vandetanib bound to its main target Protein Tyrosine Kinase 6 (PTK6) in purple, which is involved in many ... Chemotherapeutic vandetanib bound to its main target Protein Tyrosine Kinase 6 (PTK6) in purple, which is involved in many ... Chemotherapeutic Vandetanib Bound to Protein Tyrosine Kinase 6 (image). Louisiana State University ...
... we discovered that this pseudo-kinase uses the tyrosine kinase CSK to induce protein tyrosine phosphorylation in human cells. ... The pseudo-kinase and signaling protein Pragmin has been linked to cancer by regulating protein tyrosine phosphorylation via ... Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation.. Lecointre C1, Simon V1, Kerneur C1, ... These results reveal a dimerization mechanism by which a pseudo-kinase can induce protein tyrosine phosphorylation. Further ...
... which in turn may cause nitration of protein tyrosine residues. To assess the physiological role of tyrosine nitration, it is ... Phosphatidylinositol 3-kinase is a target for protein tyrosine nitration Biochem Biophys Res Commun. 1998 Nov 18;252(2):313-7. ... which in turn may cause nitration of protein tyrosine residues. To assess the physiological role of tyrosine nitration, it is ... One of these proteins was immunologically identified as the p85 regulatory subunit of the phosphatidylinositol 3-kinase, a key ...
... triggering factor via tyrosine protein kinases - Volume 120 Issue 3 - M. HAMADIEN, M. BAKHIET, R. A. HARRIS ... Lapatinib-Binding Protein Kinases in the African Trypanosome: Identification of Cellular Targets for Kinase-Directed Chemical ... Interferon-γ induces secretion of trypanosome lymphocyte triggering factor via tyrosine protein kinases. * M. HAMADIEN (a1), M ... Furthermore, IFN-γ-induced secretion was dependent on tyrosine protein kinase activity. Specific blockers of this signalling ...
The protein tyrosine kinases are a large multigene family with particular relevance to many human diseases, including ca … ... Of the 90 tyrosine kinases, 58 are receptor type, distributed into 20 subfamilies. The 32 nonreceptor tyrosine kinases can be ... The protein tyrosine kinase family of the human genome Oncogene. 2000 Nov 20;19(49):5548-57. doi: 10.1038/sj.onc.1203957. ... mouse orthologs can be identified for nearly all the human tyrosine kinases. The completion of the human tyrosine kinase family ...
... dual-specificity kinase activity, dual-specificity protein kinase, Mps1p, protein threonine/tyrosine kinase activity, ATP: ... a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.. ... Gene Ontology Term: protein serine/threonine/tyrosine kinase activity. GO ID. GO:0004712 Aspect. Molecular Function. ... dual-specificity kinase activity, dual-specificity protein kinase View GO Annotations in other species in AmiGO ...
SH2/SH3 Adaptor Proteins Can Link Tyrosine Kinases to a Ste20-related Protein Kinase, HPK1 ... Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein-tyrosine kinases.. J McGlade, A Cheng, G Pelicci, ... The Fes Protein-Tyrosine Kinase Phosphorylates a Subset of Macrophage Proteins That Are Involved in Cell Adhesion and Cell-Cell ... Calcium- and Protein Kinase C Dependent Activation of the Tyrosine Kinase PYK2 by Angiotensin II in Vascular Smooth Muscle ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). Kinase partner ... ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein] UniProt ... This protein in other organisms (by gene name): P23458 - Homo sapiens 38 * Q62126 - Mus musculus no matching PDB entries ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProt ... Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and ... This protein in other organisms (by gene name): P06241 - Homo sapiens 27 * Q3TAT3 - Mus musculus no matching PDB entries ...
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541 ...
Tyrosine-protein kinase Fgr. Details. Name. Tyrosine-protein kinase Fgr. Kind. protein. Organism. Human. Polypeptides. Name. ... Tyrosine-protein kinase Fgr. P09769. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. Pharmacological ...
Tyrosine-protein kinase ABL1. Details. Name. Tyrosine-protein kinase ABL1. Kind. protein. Organism. Human. Polypeptides. Name. ... Tyrosine-protein kinase ABL1. P00519. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. Pharmacological ...
... Summary According to the recently published report Tyrosine Protein ... Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase CYL or CSK or EC - Tyrosine-protein kinase CSK ... Tyrosine Protein Kinase CSK - Pipeline Review, H1 2020; Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase ... The report reviews Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase CYL or CSK or EC targeted ...
A. A. Akhand, M. Kato, H. Suzuki et al., "Carbonyl compounds cross-link cellular proteins and activate protein-tyrosine kinase ... P. Chiarugi and P. Cirri, "Redox regulation of protein tyrosine phosphatases during receptor tyrosine kinase signal ... H. P. Monteiro, R. J. Arai, and L. R. Travassos, "Protein tyrosine phosphorylation and protein tyrosine nitration in redox ... phosphorylation and dephosphorylation of specific tyrosine residues on the kinase protein by other PTKs or protein tyrosine ...
... Izumi Nakashima, ... Izumi Nakashima, Yoshiyuki Kawamoto, Kozue Takeda, and Masashi Kato, "Control of Genetically Prescribed Protein Tyrosine Kinase ...
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
Tyrosine kinases (PTK) represent only 10% of all protein kinases, although they are the most important protein kinases. PTKs ... 1998) Protein-tyrosine kinase and protein-serine/threonine kinase expression in human gastric cancer cell lines. J. Biomed. Sci ... Protein Tyrosine Kinase and Phosphatase Expression Profiling in Human Cancers. Wen-Chang Lin. Institute of Biomedical Sciences ... Robinson, D.R., Wu, Y.M., and Lin, S.F. (2000) The protein tyrosine kinase family of the human genome. Oncogene 19, 5548-5557. ...
... cell growth is driven by a group of enzymes known as receptor tyrosine kinases. In the current issue of the Journal of Clinical ... New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors. JCI Journals ... New class of proteins allows breast cancer cells to evade tyrosine kinase inhibitors ... known as tyrosine kinase inhibitors (TKIs) have not been effective in treating breast cancer. Researchers believe that the ...
  • CSK is a kinase that catalyzes phosphorylation of the tail tyrosine site in Src kinase. (ebi.ac.uk)
  • Stimulation of resting B lymphocytes with antibodies to surface immunoglobulin (sIgD or sIgM) induces protein tyrosine phosphorylation, implicating one or more B-cell protein-tyrosine kinases (PTKs) in sIg signal transduction. (pnas.org)
  • The recognition motif for phosphorylation by Abl is I/V/L Y XXP/F. Abl, like many cytosolic protein tyrosine kinases, preferentially phosphorylates sites recognized by its own SH2 domain, selects substrates with large hydrophobic amino acids at the +3 position and β-branched amino acids at the -1 position (4). (neb.com)
  • However, activation of SYK relies less on phosphorylation by Src family kinases than Zap-70. (wikipedia.org)
  • Experiments using temperature-sensitive v-src and v-fps mutants indicate that Shc tyrosine phosphorylation is rapidly induced upon activation of the v-Src or v-Fps tyrosine kinases. (pnas.org)
  • The efficient phosphorylation of Shc proteins and the apparent induction of their p23-binding activity in v-src- and v-fps-transformed cells are consistent with the proposition that the SH2-containing Shc polypeptides are biologically relevant substrates of the oncogenic v-Src and v-Fps tyrosine kinases. (pnas.org)
  • Following activation by PKA, the protein subsequently associates with PTK2 /FAK1, allowing PTK2 /FAK1 phosphorylation, activation and targeting to focal adhesions. (rcsb.org)
  • These mechanisms include phosphorylation and dephosphorylation of specific tyrosine residues on the kinase protein by other PTKs or protein tyrosine phosphatases (PTPs), the structures and functions of which are all under genetic control [ 2 - 8 ]. (hindawi.com)
  • For example, the catalytic activity of Src, a representative PTK, is known to be downregulated through phosphorylation of Tyr527 located in the tail of Src protein by CSK, another PTK, which leads to binding of the tail to the specific structure on the SH2 domain of Src to make the catalytic domain of Src closed [ 2 , 3 ]. (hindawi.com)
  • Lukong KE, Larocque D, Tyner AL, Richard S. Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression. (springer.com)
  • Kamalati T, Jolin HE, Fry MJ, Crompton MR. Expression of the Brk tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signaling to PI 3-kinase and Akt, via erbB3 phosphorylation. (springer.com)
  • The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. (reportbuyer.com)
  • The activation of arginase was preceded by a transient increase in intracellular cAMP, tyrosine kinase phosphorylation, and p38 mitogen-activated protein kinase (MAPK) activation. (jimmunol.org)
  • We show that a soluble Ang1 chimeric protein, COMP-Ang1, stimulates Tie1 phosphorylation in endothelial cells with similar kinetics and angiopoietin dose dependence when compared with Tie2. (sigmaaldrich.com)
  • When cotransfected, Tie2 formed heteromeric complexes with Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive Tie1 in a ligand-dependent manner. (sigmaaldrich.com)
  • In conclusion, we show that Tie1 phosphorylation is induced by multiple angiopoietin proteins and that the activation is amplified via Tie2. (sigmaaldrich.com)
  • PKC-regulated myogenesis is associated with increased tyrosine phosphorylation of FAK, Cas, and paxillin, formation of Cas-CRK complex, and JNK activation. (umassmed.edu)
  • Syndecan-4 modulates focal adhesion kinase phosphorylation. (umassmed.edu)
  • JAK3 is predomintly expressed in immune cells and transduces a sigl in response to its activation via tyrosine phosphorylation by interleukin receptors. (acris-antibodies.com)
  • c-Abl-dependent phosphorylation of CSB increased in cells treated with hydrogen peroxide and decreased in cells pre-treated with STI-571, a c-Abl-specific protein kinase inhibitor. (harvard.edu)
  • Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. (rupress.org)
  • We have investigated mechanisms involved in integrin-mediated signal transduction in platelets by examining integrin-dependent phosphorylation and activation of a newly identified protein tyrosine kinase, pp125FAK (FAK, focal adhesion kinase). (rupress.org)
  • We show that thrombin and collagen activation of platelets causes an induction of tyrosine phosphorylation of pp125FAK and that pp125FAK molecules isolated from activated platelets display enhanced levels of phosphorylation in immune-complex kinase assays. (rupress.org)
  • Fibrinogen binding to GP IIb-IIIa was not sufficient to induce pp125FAK phosphorylation because pp125FAK was not phosphorylated on tyrosine in thrombin-treated platelets that were not allowed to aggregate. (rupress.org)
  • These results indicate that tyrosine phosphorylation of pp125FAK is dependent on platelet aggregation mediated by fibrinogen binding to the integrin receptor GP IIb-IIIa. (rupress.org)
  • The induction of tyrosine phosphorylation of pp125FAK was inhibited in thrombin- and collagen-treated platelets preincubated with cytochalasin D, which prevents actin polymerization following activation. (rupress.org)
  • Under all of these conditions, there was a strong correlation between the induction of tyrosine phosphorylation of pp125FAK in vivo and stimulation of the phosphorylation of pp125FAK in vitro in immune-complex kinase assays. (rupress.org)
  • This study provides the first genetic evidence that tyrosine phosphorylation of pp125FAK is dependent on integrin-mediated events, and demonstrates that there is a strong correlation between tyrosine phosphorylation of pp125FAK in platelets, and the activation of pp125FAK-associated phosphorylating activity in vitro. (rupress.org)
  • OVA-induced Src phosphorylation was abrogated by Src inhibitors, but not affected by inhibitors of EGFR and Rho-kinase. (ahajournals.org)
  • Inhibitors of Src and EGFR, but not Rho-kinase, also blocked OVA-induced EGFR phosphorylation. (ahajournals.org)
  • Tyrosine phosphorylation of GIV and its association with p85α increased during metastatic progression of a breast carcinoma. (sciencemag.org)
  • These results suggest a mechanism by which multiple receptors activate PI3K through tyrosine phosphorylation of GIV, thereby making the GIV-PI3K interaction a potential therapeutic target within the PI3K-Akt pathway. (sciencemag.org)
  • Expression of PAG in COS cells results in recruitment of endogenous Csk, altered Src kinase activity, and impaired phosphorylation of Src-specific substrates. (rupress.org)
  • The association of Pyk2 with Lyn was dependent on stimulation with MCP-1 and on tyrosine phosphorylation of Pyk2. (portlandpress.com)
  • Phosphorylation of p38 was also dependent on tyrosine phosphorylation of Pyk2. (portlandpress.com)
  • Phosphorylation of ERK (extracellular-signal-regulated protein kinase) was not affected by overexpression of kinase-negative Pyk2. (portlandpress.com)
  • The ability of the tyrphostins to inhibit the EGFRK activity in cardiac membranes was determined by monitoring tyrosine phosphorylation of either the 170 kDa protein or immunoprecipitated EGF receptor at 0° and room temperature, respectively. (amrita.edu)
  • However, the increase in tyrosine phosphorylation of p130cas was not restricted to differentiation inducing stimuli. (diva-portal.org)
  • The phosphorylation was blocked by the specific PKC inhibitor GF 109203X, and transient transfection with active PKC-epsilon induced p130cas tyrosine phosphorylation. (diva-portal.org)
  • pp60c-src, known to directly phosphorylate p130cas in other cell systems, was not activated after stimulation with TPA or bFGF/IGF-I for up to 30 min, and the initial p130cas phosphorylation was resistant to the Src family kinase inhibitor herbimycin A. However, in long term stimulated cells, herbimycin A blocked the induced phosphorylation of p130cas. (diva-portal.org)
  • The cGMP sensitivity of cyclic nucleotide-gated (CNG) channels can be modulated by changes in phosphorylation catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases. (rupress.org)
  • Our recent work shows that CNG channels in rod outer segments are subject to modulation by changes in tyrosine phosphorylation, the final step in a biochemical cascade in which neuromodulators can alter the rod light response (Savchenko, Kraft, Molokanova, Kramer, manuscript in preparation). (rupress.org)
  • A polymer, the tails of the intracellular domains of the two receptors are in contact with one another, activating the function of their protein kinases, Phosphorylation results in the assembly of the tail of the receptor's intracellular domain into a signaling complex. (creativebiomart.net)
  • The newly phosphorylated tyrosine site immediately becomes the binding site for intracellular signaling proteins, and there may be 10 to 20 different intracellular signaling proteins that are activated after binding to the receptor phosphorylation site. (creativebiomart.net)
  • Phosphorylation of specific tyrosine residues within an activating receptor provides a binding site for proteins containing the SH2 domain and the phosphotyrosine binding (PTB) domain. (creativebiomart.net)
  • Phosphorylation and activation of these two proteins that bind to the receptor triggers a signal transduction pathway. (creativebiomart.net)
  • Carboxy-terminal Src kinase (Csk) is a ubiquitously expressed nonreceptor tyrosine kinase that negatively regulates the Src family kinases (SFKs) by phosphorylation of the SFK carboxy-terminal tyrosine (1,2). (creativebiomart.net)
  • however, drugs that target RTKs, known as tyrosine kinase inhibitors (TKIs) have not been effective in treating breast cancer. (eurekalert.org)
  • Tyrosine kinase inhibitors (TKIs) are used as targeted drugs for advanced renal cell carcinoma (RCC), although most cases eventually progress by acquiring resistance. (nature.com)
  • Fig. 6: DPP4 inhibitor therapy potentially improves prognosis and tumor regression of renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). (nature.com)
  • Traxler, Protein Tyrosine Kinase Inhibitors in Cancer Treatment, Expert Opinion on Therapeutic Patents, 7(6):571-588, 1997. (patentgenius.com)
  • The induction of arginase was abolished by a protein kinase A (PKA) inhibitor, KT5720, and was down-regulated by tyrosine kinase inhibitors and a p38 MAPK inhibitor, SB203580. (jimmunol.org)
  • Furthermore, the induction of arginase was insensitive to the protein kinase C and p44/p42 MAPK kinase inhibitors. (jimmunol.org)
  • Aortic contraction by OVA was significantly blocked not only by Rho kinase inhibitors Y-27632 and hydroxyfasudil, but also by Src inhibitors PP2 and Src inhibitor No. 5 and the EGFR inhibitors AG1478 and EGFR inhibitor 1. (ahajournals.org)
  • A unique collection of 319 protein kinase inhibitors for high throughput screening (HTS) and high content screening (HCS). (medchemexpress.com)
  • Some protein kinase inhibitors have been approved by FDA. (medchemexpress.com)
  • For that reason a TR-FRET screening assay, such as the one described here, can aid in elucidating specific inhibitors for tyrosine kinases. (bmglabtech.com)
  • Several FLT3 kinase inhibitors (FLT3-TKI) have been clinically tested but none is yet approved for the therapy of AML ( 5, 6 ). (aacrjournals.org)
  • Enzymes known as kinase inhibitors stop cancerous cells from dividing and developing. (einpresswire.com)
  • Since the first protein kinase inhibitor was developed in the early 1980s, the FDA has approved 37 kinase inhibitors for the treatment of cancers such as breast and lung cancer. (einpresswire.com)
  • Some of the key factors driving market growth include increased acceptance of kinase inhibitors, a surge in product approvals, a rise in the occurrence of cancer diseases, and increased investment from pharmaceutical companies. (einpresswire.com)
  • Furthermore, the increased use of kinase inhibitors for newer applications, as well as emerging economies like China and India, would provide new opportunities for the global kinase inhibitors industry. (einpresswire.com)
  • ALW-II-41-27 is a novel Eph receptor tyrosine kinase inhibitor. (adooq.com)
  • Fig. 2: DPP4 inhibition enhances tumor-suppressive efficacy of tyrosine kinase inhibitor sunitinib in patient-derived renal cell carcinoma (RCC) spheroid cultures. (nature.com)
  • Orthovanadate (OVA), a protein tyrosine phosphatase (PTPase) inhibitor, exerts contractile effects on smooth muscle in a Rho-kinase-dependent manner, but the precise mechanisms are not elucidated. (ahajournals.org)
  • Here, we demonstrate that cotreatment with JQ1 and the FLT3 tyrosine kinase inhibitor (TKI) ponatinib or AC220 synergistically induce apoptosis of cultured and primary CD34 + human AML blast progenitor cells (BPC) expressing FLT3-ITD. (aacrjournals.org)
  • Tyrphostin also known as AG 808 is a protein tyrosine Kinase inhibitor. (agscientific.com)
  • Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. (uni-wuerzburg.de)
  • By product, the Global protein tyrosine kinase 7 Market is segmented into Epidermal growth factor receptor tyrosine kinase inhibitor, BCR-ABL Tyrosine kinase inhibitor, vascular endothelial growth factor tyrosine kinase inhibitor and others. (einpresswire.com)
  • Abl contains 407 amino acids (residues 237-643 of the p120-gag-abl polyprotein), which include the kinase catalytic domain, SH2 domain on the N-terminus and the I237M mutation. (neb.com)
  • A major mechanism of injury associated with the production of nitric oxide (NO*) in vivo is due to its diffusion-limited reaction with superoxide to form peroxynitrite, which in turn may cause nitration of protein tyrosine residues. (nih.gov)
  • c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (wikipedia.org)
  • It phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs). (reportlinker.com)
  • The amino acids at positions three and five within the conserved sequence are leucine (L) residues in TYRO3 and isoleucine (I) residues in the related receptor tyrosine kinases, AXL and MERTK. (atlasgeneticsoncology.org)
  • 2004). Three tyrosine residues (Y681, Y685, Y686) located within the activation loop of the kinase domain of the TYRO3 receptor correspond to three tyrosine residues in the MERTK receptor kinase domain, which have been identified as sites of autophosphorylation, however, there is no direct evidence that Y681, Y685, and Y686 are autophosphorylated in the TYRO3 receptor (Linger et al. (atlasgeneticsoncology.org)
  • This protein phosphorylates specific tyrosine residues in other protein s. (wikidoc.org)
  • A large class of enzymes that catalyse the transfer of phosphate from ATP to tyrosine residues in polypeptides. (thefreedictionary.com)
  • detailed analysis disclosed either genomic DNA deletions in the region encompassing Btk or missense point mutations resulting in nonconservative amino acid substitutions at important residues in the putative protein-tyrosine kinase domain (89). (thefreedictionary.com)
  • Individual replacement of the two cysteine residues within the first 10 amino acids of p59fyn and p56lck with serine indicated that Cys3 was the major determinant of palmitoylation, as well as association of the PTK with glycosyl-phosphatidylinositol-anchored proteins. (rupress.org)
  • PAG comprises a short extracellular domain of 16 amino acids and a 397-amino acid cytoplasmic tail containing ten tyrosine residues that are likely phosphorylated by Src family kinases. (rupress.org)
  • Similarly, the transmembrane protein LAT is targeted to GEMs of T lymphocytes by palmitoylation of two membrane-proximal cysteine residues ( 15 ). (rupress.org)
  • These interactions are dependent on the RTK kinase activity and autophosphorylation of specific tyrosine residues in the carboxyl terminus. (aspetjournals.org)
  • Epidermal growth factor receptor (EGFR) BRET structure-function studies identify the tyrosine residues 1068, 1114, and 1148 as the main residues mediating the interaction of EGFR with the adapter protein Grb2. (aspetjournals.org)
  • Many of the RTK-effector protein interactions depend on the autophosphorylation of specific tyrosine residues in the intracellular carboxyl terminus of an RTK. (aspetjournals.org)
  • Protein receptor tyrosine kinases (RTKs) are the largest class of enzyme-linked receptors, both receptors and enzymes that bind to ligands and phosphorylate tyrosine residues of target proteins. (creativebiomart.net)
  • Since the RTK receptor phosphorylates multiple tyrosine residues, they can activate a variety of signal transduction pathways. (creativebiomart.net)
  • Sekimoto H, Eipper-Mains J, Pond-Tor S, Boney CM. (alpha)v(beta)3 integrins and Pyk2 mediate insulin-like growth factor I activation of Src and mitogen-activated protein kinase in 3T3-L1 cells. (umassmed.edu)
  • Knockdown of Brk by stable expression of short hairpin RNA (shRNA) in T47D breast cancer cells decreases proliferation and blocks epidermal growth factor (EGF)- and heregulin-induced activation of Rac GTPase, extracellular signal-regulated kinase (ERK) 5, and p38 mitogen-activated protein kinase (MAPK) but not Akt, ERK1/2, or c-Jun NH 2 -terminal kinase. (aacrjournals.org)
  • The intracellular protein tyrosine kinase, PTK6 (also known as the breast tumor kinase, Brk), has been implicated in the development and progression of a number of different tumor types. (springer.com)
  • Castro NE, Lange CA. Breast tumor kinase and extracellular-signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells. (springer.com)
  • Breast tumor kinase (protein tyrosine kinase 6) regulates heregulin-induced activation of ERK5 and p38 MAP kinases in breast cancer cells. (springer.com)
  • Breast tumor kinase (Brk/PTK6) plays a role in the differentiation of primary keratinocytes. (springer.com)
  • Role of breast tumor kinase in the in vitro differentiation of HaCaT cell. (springer.com)
  • Breast tumor kinase (Brk) is a soluble tyrosine kinase that was cloned from a metastatic breast tumor. (aacrjournals.org)
  • Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. (axonmedchem.com)
  • Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression. (axonmedchem.com)
  • The present invention relates to compounds of the Formula I, the pharmaceutically acceptable salts and stereoisomers thereof, which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent. (google.com)
  • We now present biochemical evidence for Jak-family kinase involvement in IFN signal transduction. (nih.gov)
  • Analysis of how these adapter proteins bind to the Met receptor and what signal transducers they recruit have led to more substantial models of HGF/SF-Met signal transduction and have uncovered new potential pathways that may be involved into Met mediated tumor cell invasion and metastasis. (nih.gov)
  • One of these proteins was immunologically identified as the p85 regulatory subunit of the phosphatidylinositol 3-kinase, a key enzyme involved in the signal transduction cascade initiated by many agonists including growth factors. (nih.gov)
  • Activated tyrosine kinases therefore regulate the association of Shc proteins with p23 and may thereby control the stimulation of an Shc-mediated signal transduction pathway. (pnas.org)
  • Receptor protein-tyrosine kinases and their signal transduction pathways. (thefreedictionary.com)
  • Cellular interactions and signal transduction must be an important aspect of hindbrain segmentation, so we have screened for tyrosine kinases expressed in rhombomere-restricted patterns in the developing mouse embryo. (biologists.org)
  • Signal transduction by immunoreceptors (TCRs, B cell receptors, and most Fc receptors) after their aggregation by natural ligands or Abs is initiated by activation of protein tyrosine kinases (PTKs) of the Src and Syk families, which phosphorylate a variety of substrates, thus allowing propagation of the initial stimulus to cytosolic signaling pathways ( 1 ). (rupress.org)
  • In the present study we investigated the role of tyrosine kinases such as proline-rich tyrosine kinase 2 (Pyk2) in MCP-1-mediated signal transduction in the monocytic cell line THP-1. (portlandpress.com)
  • These adaptor proteins associate RTK activation with downstream signal transduction pathways, such as the MAP kinase signaling cascade. (creativebiomart.net)
  • An important signal transduction pathway contains the tyrosine kinase receptor c-met, which is required for the survival and proliferation of myoblasts during migration during muscle development. (creativebiomart.net)
  • Aberrant regulation of cell growth pathways is required for normal cells to become cancerous, and in many types of cancer, cell growth is driven by a group of enzymes known as receptor tyrosine kinases (RTKs). (eurekalert.org)
  • Shown are examples of mutations (A), amplifications (B), or translocations (C) that render a kinase constitutively active and thus contribute to the addiction of tumor cells on pathways driven by the genetically altered kinase. (asm.org)
  • 2002) Thrombopoietin regulates Bcl-xL gene expression through Stat5 and phosphatidylinositol 3-kinase activation pathways. (acris-antibodies.com)
  • 2002) UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. (acris-antibodies.com)
  • These results suggest that Brk may be regulated differently than other Src family tyrosine kinases and/or that Brk may interact with novel signaling pathways. (aacrjournals.org)
  • It activates several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. (medgadget.com)
  • RTK BRET-2 assays monitor, in living cells, the specific interaction between RTKs and their effector proteins, which control the activation of specific downstream signaling pathways. (aspetjournals.org)
  • They control the assembly of larger protein complexes that are involved in building, shaping, and directing specific RTK signaling pathways (illustrated in Fig. 1a ) ( Schlessinger, 2000 ). (aspetjournals.org)
  • Among the many enzymes, protein tyrosine kinases (PTKs) are known to play key roles in intracellular signaling for the development and functions of cells [ 1 ]. (hindawi.com)
  • Myelin is composed of a limited number of myelin proteins: proteolipid protein (PLP), myelin basic protein (MBP), 2′, 3′-cyclic nucleotide 3′-phosphohydrolase (CNPase), MAG, and several enzymes. (jneurosci.org)
  • PTK6 is related to the Src family of protein kinases and belongs to a distinct class of enzymes which includes Frk and SRMS (reviewed Harvey and Burmi 2011 ) and expression produces two different isoforms as a result of alternative splicing (reviewed in. (springer.com)
  • Protein Kinase C (PKC) enzymes are a diverse family of enzymes that under specific signaling conditions phosphorylate proteins on serine and threonine amino acids. (bmglabtech.com)
  • Tyrosine kinases (TKs) are a diverse family of enzymes that under specific signaling conditions phosphorylate proteins on the amino acid tyrosine. (bmglabtech.com)
  • Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT . (rcsb.org)
  • The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of β-catenin. (springer.com)
  • Together, these data demonstrate for the first time that IL-13 down-regulates NO production through arginase induction via cAMP/PKA, tyrosine kinase, and p38 MAPK signalings and underline the importance of arginase in the immunosuppressive activity of IL-13 in activated macrophages. (jimmunol.org)
  • 2002) Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line. (acris-antibodies.com)
  • 2001) Thrombin regulates vascular smooth muscle cell growth and heat shock proteins via the JAK-STAT pathway. (acris-antibodies.com)
  • Objective- G protein-coupled receptor kinase-5 (GRK5) is a widely expressed Ser/Thr kinase that regulates several atherogenic receptors and may activate or inhibit nuclear factor-κB (NF-κB). (ahajournals.org)
  • Fer is a ubiquitously expressed non-receptor protein-tyrosine kinase that regulates normal physiology through signaling in a variety of cell types. (queensu.ca)
  • The Met receptor tyrosine kinase is the prototypic member of a small subfamily of growth factor receptors that when activated induce mitogenic, motogenic, and morphogenic cellular responses. (nih.gov)
  • c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. (wikipedia.org)
  • 1994). Following ligand binding to the extracellular domain, the TYRO3 receptors dimerize and autophosphorylation of the tyrosine kinase domain occurs. (atlasgeneticsoncology.org)
  • adhesion receptors , receptor tyrosine kinases , G-protein coupled receptors and cytokine receptors . (wikidoc.org)
  • It assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. (reportbuyer.com)
  • A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity. (umassmed.edu)
  • JAK2 (Janus Kinase 2) belongs to the emerging family of non-receptor Janus tyrosine kinases, which regulate a spectrum of cellular functions downstream of activated cytokine receptors in the lympho-hematopoietic system. (acris-antibodies.com)
  • G protein-coupled receptor kinase-5 (GRK5) is a ubiquitously expressed member of the GRK family of Ser/Thr kinases, originally characterized for their ability to phosphorylate agonist-activated 7-transmembrane receptors. (ahajournals.org)
  • The ontogeny of the structural and functional characteristics of insulin receptors is determined by examining insulin binding, subunit structure, autophosphorylation, and tyrosine-specific protein kinase activity in partially purified solubilized liver receptors from fetal (∼21 days postconception), neonatal (1- and 7-day-old), and adult rats. (diabetesjournals.org)
  • also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5′-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. (sciencemag.org)
  • Upon ligand stimulation of various receptors, GIV was phosphorylated at tyrosine-1764 and tyrosine-1798 by both receptor and non-receptor tyrosine kinases. (sciencemag.org)
  • Human epidermal growth factor receptor 2 (ERBB2, NEU, or HER2) is a type I membrane glycoprotein that is a member of the ERBB family of tyrosine kinase receptors. (perkinelmer.com)
  • Receptor tyrosine kinases (RTKs) represent a broad class of cell surface receptors that transduce signals across the cell membrane and regulate cell proliferation, survival, differentiation and migration ( Schlessinger, 2000 ). (aspetjournals.org)
  • This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)
  • It could be that the catalytic activities of PTKs are upregulated through redox mechanism-based inactivation of PTPs which otherwise dephosphorylate phosphorylated tyrosines at the major autophosphorylation sites of PTKs [ 11 - 14 ]. (hindawi.com)
  • Among a variety of sites, Tyrosines 1007 and 1008 are sites of trans- or autophosphorylation in vivo and in in vitro kinase reactions. (acris-antibodies.com)
  • Here we show that CK2 α/α′ subunits undergo intermolecular ( trans ) tyrosine-autophosphorylation, which is dependent on intrinsic catalytic activity and is suppressed by the individual mutation of Tyr 182 , a crucial residue of the activation loop, to phenylalanine. (biochemj.org)
  • At variance with serine-autophosphorylation, tyrosine-autophosphorylation of CK2α is reversed by ADP and GDP and is counteracted by the β-subunit and by a peptide reproducing the activation loop of CK2α/α′ (amino acids 175-201). (biochemj.org)
  • The 32 nonreceptor tyrosine kinases can be placed in 10 subfamilies. (nih.gov)
  • 2003) Distinct mechanisms of receptor and nonreceptor tyrosine kinase activation by reactive oxygen species in vascular smooth muscle cells: role of metalloprotease and protein kinase C-delta. (acris-antibodies.com)
  • The kinetics of activation of these kinases, particularly that of p56blk, paralleled the early appearance of newly tyrosine-phosphorylated B-cell proteins, suggesting that this group of kinases may account for some portion of the tyrosine kinase activity in sIg-activated B cells. (pnas.org)
  • Furthermore, IFN-γ-induced secretion was dependent on tyrosine protein kinase activity. (cambridge.org)
  • c-Src should not be confused with CSK (C-terminal Src kinase), an enzyme that phosphorylates c-Src at its C-terminus and provides negative regulation of Src's enzymatic activity. (wikipedia.org)
  • On the other hand, dephosphorylation of phosphorylated Tyr416 by PTPs downregulates the kinase activity [ 5 , 6 , 8 ]. (hindawi.com)
  • Proteins binding to this region were found by gel shift study, and the binding activity correlates with Fyn activity during myelination. (jneurosci.org)
  • Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. (springer.com)
  • Activation of the co-receptor complex transduces a signal, which in turn, stimulates tyrosine kinase activity in the intracellular domain. (ganfyd.org)
  • An elevated level of activity of c-Src tyrosine kinase is suggested to be linked to cancer progression by promoting other signals. (wikidoc.org)
  • Results showed that IL-13 increased arginase activity through de novo synthesis of the arginase I mRNA and protein. (jimmunol.org)
  • Additionally, we demonstrate that in detergent conditions (1% Nonidet P-40 (NP-40)) which disrupt the association between mIg and the MB-1/B29 heterodimer, no protein tyrosine kinase activity can be detected in association with mIg. (jimmunol.org)
  • These data support the hypothesis that the MB-1/B29 heterodimer couples the antigen receptor to protein tyrosine kinases, thereby providing a physical link that facilitates Ag receptor-mediated regulation of kinase activity. (jimmunol.org)
  • Its activation is highly correlated with the stimulation of c-Jun N-terminal kinase activity. (hmdb.ca)
  • an index of Rho-kinase activity) in vascular smooth muscle cells (VSMCs). (ahajournals.org)
  • GRK5 activity in monocytes also reduced migration promoted by the 7-transmembrane receptor for monocyte chemoattractant protein-1 CC chemokine receptor-2. (ahajournals.org)
  • 16 Lastly, GRK5 phosphorylates the platelet-derived growth factor receptor-β (PDGFRβ) and thereby alters signaling through this proatherogenic receptor tyrosine kinase in vascular smooth muscle cells (SMCs)-by reducing PDGFRβ-triggered inositol phosphate signaling, reducing PDGFRβ catalytic activity, and enhancing PDGFRβ-dependent Src activation. (ahajournals.org)
  • Total tyrosine kinase activity is often elevated in both cytosolic and membrane fractions of malignant breast tissue and correlates with a decrease in disease-free survival. (aacrjournals.org)
  • In addition to overexpression of ErbB family members, total tyrosine kinase activity is often enhanced in both cytosolic and membrane fractions of malignant breast tissue and correlates with a decrease in disease-free survival. (aacrjournals.org)
  • To our knowledge, this is the first demonstration that antibody-mediated inhibition of RON receptor tyrosine kinase activity negatively influences the proliferation of colon cancer cells in vitro and in vivo . (aacrjournals.org)
  • With fixed amounts of protein, the tyrosine-specific protein kinase activity in the presence of different insulin concentrations (1 × 10 −8 to 1 × 10 −6 M) was significantly higher in the fetal and neonatal rats than in adult rats. (diabetesjournals.org)
  • However, when expressed as a function of insulin-binding activity, the insulin-stimulated tyrosine-specific protein kinase activity in fetal and neonatal rats appears to be similar to that in adult rats because of decreased insulin binding in the latter group. (diabetesjournals.org)
  • In vitro for inhibitory activity against tyrosine specific protein kinase from murine spleen cells (T-kinase). (nih.gov)
  • Employing purified protein phosphotyrosine phosphatase, and benzylidene derivatives (tyrphostins: compounds 11 and 12) that selectively inhibit EGF receptor protein tyrosine kinase (EGFRK) activity, the role of EGFRK in EGF-mediated stimulation of cardiac adenylyl cyclase was investigated. (amrita.edu)
  • Compounds 11 and 12, in a concentration-dependent manner, inhibited EGF receptor tyrosine kinase activity. (amrita.edu)
  • Thus, we conclude that protein tyrosine kinase activity of the EGF receptor is essential for the stimulation of cardiac adenylyl cyclase by EGF. (amrita.edu)
  • Dr. Bipin G. Nair and Tarun B Patel, "Regulation of cardiac adenylyl cyclase by Epidermal Growth Factor (EGF): Role of EGF receptor protein tyrosine kinase activity", Biochemical pharmacology, vol. 46, pp. 1239-1245, 1993. (amrita.edu)
  • Fractionation of this protein-tyrosine kinase activity by chromatography on DEAE-cellulose yields a major diffuse peak of activity. (biochemj.org)
  • We have now partially purified the early-eluting peak of kinase activity by chromatography on columns of butyl-agarose, protamine-agarose and Sephacryl S200. (biochemj.org)
  • Upon cell activation, guanine exchange factors stimulate the exchange of GTP for GDP and thereby activate the Rho GTPases, whereas the GTPase activating proteins turn off the Rho GTPase by stimulating their inherent GTP-hydrolysis activity. (diva-portal.org)
  • In conclusion, our data supports the notion that RhoGAPs are multi-functional proteins, fulfilling not only the role as downregulators of Rho GTPase activity, but also as signal transducers of numerous vital cellular processes. (diva-portal.org)
  • A limited number of whole-cell assays allow monitoring of receptor tyrosine kinase (RTK) activity in a signaling pathway-specific manner. (aspetjournals.org)
  • All RPTKs are composed of three components: an extracellular domain containing a ligand binding site, a single transmembrane hydrophobic alpha helix region, and an intracellular domain containing tyrosine protein kinase (RTKs) activity. (creativebiomart.net)
  • Other proteins that interact with the activating receptor act as adaptor proteins and have no intrinsic enzymatic activity by themselves. (creativebiomart.net)
  • Recent observations on environment-linked control of genetically prescribed signaling systems for either cell activation or cell death have been reviewed with a focus on the regulation of activities of protein tyrosine kinases (PTKs). (hindawi.com)
  • ROS thus generated might upregulate the catalytic activities of PTKs through inactivating protein tyrosine phosphatases that dephosphorylate and inactivate autophosphorylated PTKs. (hindawi.com)
  • Recent evidence has, however, demonstrated that ROS could also directly oxidize SH groups of genetically conserved specific cysteines on PTKs, sometimes producing disulfide-bonded dimers of PTK proteins, either for upregulation or downregulation of their catalytic activities. (hindawi.com)
  • Protein tyrosine phosphatases (PTP) attenuate growth signals generated by the PTKs through catalyzing the tyrosine dephosphorylation step on their substrate proteins. (sigmaaldrich.com)
  • Recent work has demonstrated that p56lck, a member of the Src family of protein tyrosine kinases (PTKs), is modified by palmitoylation of a cysteine residue(s) within the first 10 amino acids of the protein (in addition to amino-terminal myristoylation that is a common modification of the Src family of PTKs). (rupress.org)
  • Several transforming viruses contain "Immunoreceptor Tyrosine Activation Motifs" (ITAMs) which lead to activation of Syk including Epstein Barr virus, bovine leukemia virus, and mouse mammary tumor virus. (wikipedia.org)
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)
  • Over the last decade, major advances have been made in the elucidation of mechanisms involved in leukemogenesis, and this is particularly true with regard to deregulated protein tyrosine kinase (PTK) activation. (haematologica.org)
  • It is known that cross-linking of the B cell Ag receptor results in protein tyrosine kinase activation. (jimmunol.org)
  • lin-15 acts non-cell-autonomously to prevent the activation of a receptor tyrosine kinase/ras signaling pathway. (genetics.org)
  • Mechanisms of mutated and wild-type tyrosine kinase activation in cancer. (asm.org)
  • Three prototypical mechanisms of genetically altered tyrosine kinase activation as evidenced through genetic alterations. (asm.org)
  • Insulin stimulates spreading of skeletal muscle cells involving the activation of focal adhesion kinase, phosphatidylinositol 3-kinase and extracellular signal regulated kinases. (umassmed.edu)
  • Involved in calcium induced regulation of ion channel and activation of the map kinase signaling pathway. (hmdb.ca)
  • 2002) 5(S)-hydroxyeicosatetraenoic acid stimulates DNA synthesis in human microvascular endothelial cells via activation of Jak/STAT and phosphatidylinositol 3-kinase/Akt signaling, leading to induction of expression of basic fibroblast growth factor 2. (acris-antibodies.com)
  • Activation of the c-Abl kinase in response to oxidative damage is not observed in CSB null cells. (harvard.edu)
  • The relative differences in insulin-mediated biological functions in fetal and adult rat livers as reported previously are due to alterations ina step(s) distal to activation of insulin-receptor kinase. (diabetesjournals.org)
  • These are heterotrimeric G proteins, Src family kinases, and the recently cloned transmembrane adaptor protein linker for activation of T cells (LAT). (rupress.org)
  • The cell signaling docking protein p130cas became tyrosine-phosphorylated in SH-SY5Y human neuroblastoma cells during induced differentiation with 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum or a combination of basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I). The differentiating cells develop a neuronal phenotype with neurites and growth cones and sustained activation of protein kinase C (PKC) and pp60c-src. (diva-portal.org)
  • Our data suggest that BFT-stimulated IL-8 secretion involves tyrosine kinase-dependent activation of nuclear factor-κB (NF-κB) as well as activation of the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-related kinase. (asm.org)
  • Results: Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). (uni-wuerzburg.de)
  • This article is about the kinase c-Src, for the kinase that phosphorylates c-Src, see CSK . (wikidoc.org)
  • In addition, c-Abl kinase phosphorylates CSB at Tyr932. (harvard.edu)
  • Schneider GB, Gilmore AP, Lohse DL, Romer LH, Burridge K. Microinjection of protein tyrosine phosphatases into fibroblasts disrupts focal adhesions and stress fibers. (umassmed.edu)
  • Similar complexes between ion channels, protein kinases, and protein phosphatases have been shown for several other channels ( Levitan 1999 ) and may be the rule rather than the exception. (rupress.org)
  • Catalytic specificity of protein-tyrosine kinases is critical for selective signalling. (harvard.edu)
  • Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that is distantly related to SRC family kinases. (wiley.com)
  • Although Brk is ∼56% homologous to c-Src within the kinase domain and similarly encodes a "soluble" tyrosine kinase with tandem NH 2 -terminal SH3 and SH2 domains, Brk is a member of a novel family of soluble protein tyrosine kinases, considered to be distantly related to c-Src ( 6 ). (aacrjournals.org)
  • EC belongs to the non-receptor tyrosine kinases, distantly related to the c- Src family kinases, with occurrence in the cytoplasma. (axonmedchem.com)
  • We identified AKT, p130CAS and focal adhesion kinase (FAK) as novel PTK6 substrates and demonstrated their roles in promoting cell proliferation, migration and resistance to anoikis. (wiley.com)
  • 1994). The two Ig domains and two FNIII domains define TYRO3 as a member of a family of receptor tyrosine kinases (RTKs), which also includes AXL and MERTK . (atlasgeneticsoncology.org)
  • A total of 22 BRET assays have been established for nine RTKs derived from four subfamilies [erythroblastic leukemia viral (v-erb-b) oncogene homolog (ErbB), platelet-derived growth factor (PDGF), neurotrophic tyrosine kinase receptor (TRK), vascular endothelial growth factor (VEGF)] monitoring the interactions with five effectors (Grb2, p85, Stat5a, Shc46, PLCγ1). (aspetjournals.org)
  • Receptor tyrosine kinase (RTKs) is a high affinity cell surface receptor for many polypeptide growth factors, cytokines and hormones. (creativebiomart.net)
  • Most studies have looked at the receptor tyrosine kinases and examples of these are platelet derived growth factor receptor (PDGFR) pathway and epidermal growth factor receptor (EGFR). (wikipedia.org)
  • Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:7615558). (rcsb.org)
  • The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins. (genetics.org)
  • In the absence of genetic alterations (D to F), nonmutated tyrosine kinases can be activated via many different mechanisms and contribute to pathway signaling. (asm.org)
  • 2000) Reactive oxygen species regulate heat shock protein 70 via the JAK/STAT Pathway. (acris-antibodies.com)
  • These proteins were also recognized by polyclonal anti-peptide antibodies raised against the C-terminal 33 amino acids of p56lck, a major T lymphocyte protein-tyrosine kinase. (biochemj.org)
  • Antibodies raised against a peptide corresponding to amino acids 39-64 of p56lck, a sequence found near the N-terminus, recognized the slower-migrating, but not the faster-migrating, form of the enzyme, indicating that a fraction of the protein had been proteolysed near the N-terminus during purification. (biochemj.org)
  • A new independent 61 page research with title 'Proto Oncogene Tyrosine Protein Kinase ROS {Proto Oncogene c Ros 1 or Receptor Tyrosine Kinase c Ros Oncogene 1 or c Ros Receptor Tyrosine Kinase or ROS1 or EC} - Pipeline Review, H2 2017' guarantees you will remain better informed than your competition. (medgadget.com)
  • The latest report Proto Oncogene Tyrosine Protein Kinase ROS - Pipeline Review, H2 2017, outlays comprehensive information on the Proto Oncogene Tyrosine Protein Kinase ROS (Proto Oncogene c Ros 1 or Receptor Tyrosine Kinase c Ros Oncogene 1 or c Ros Receptor Tyrosine Kinase or ROS1 or EC targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (medgadget.com)
  • Global Markets Direct's, 'Tyrosine Protein Kinase JAK1 (Janus Kinase 1 or JAK1 or EC Pipeline Review, H2 2019', provides in depth analysis on Tyrosine Protein Kinase JAK1 (Janus Kinase 1 or JAK1 or EC targeted pipeline therapeutics. (globalmarketsdirect.com)
  • Proto Oncogene Tyrosine Protein Kinase ROS (Proto Oncogene c Ros 1 or Receptor Tyrosine Kinase c Ros Oncogene 1 or c Ros Receptor Tyrosine Kinase or ROS1 or EC pipeline Target constitutes close to 6 molecules. (medgadget.com)
  • Proto Oncogene Tyrosine Protein Kinase ROS (Proto Oncogene c Ros 1 or Receptor Tyrosine Kinase c Ros Oncogene 1 or c Ros Receptor Tyrosine Kinase or ROS1 or EC - Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ROS1 gene. (medgadget.com)
  • Furthermore, this report also reviews key players involved in Proto Oncogene Tyrosine Protein Kinase ROS (Proto Oncogene c Ros 1 or Receptor Tyrosine Kinase c Ros Oncogene 1 or c Ros Receptor Tyrosine Kinase or ROS1 or EC targeted therapeutics development with respective active and dormant or discontinued projects. (medgadget.com)
  • Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC pipeline Target constitutes close to 23 molecules. (reportsweb.com)
  • Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC tyrosine-protein kinase erbB-3 or HER3 is a membrane bound protein encoded by the ERBB3 gene. (reportsweb.com)
  • It also reviews key players involved in Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC targeted therapeutics development with respective active and dormant or discontinued projects. (reportsweb.com)
  • Tyrosine Protein Kinase Fyn (Proto Oncogene Syn or Proto Oncogene c Fyn or Src Like Kinase or p59 Fyn or FYN or EC pipeline Target constitutes close to 8 molecules. (researchandmarkets.com)
  • Tyrosine Protein Kinase Fyn (Proto Oncogene Syn or Proto Oncogene c Fyn or Src Like Kinase or p59 Fyn or FYN or EC - Proto-oncogene tyrosine-protein kinase Fyn is an enzyme encoded by the FYN gene. (researchandmarkets.com)
  • Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase CYL or CSK or EC pipeline Target constitutes close to 12 molecules. (reportlinker.com)
  • Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase CYL or CSK or EC - Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. (reportlinker.com)
  • It also reviews key players involved in Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase CYL or CSK or EC targeted therapeutics development with respective active and dormant or discontinued projects. (reportlinker.com)
  • Tyrosine Protein Kinase SYK (Spleen Tyrosine Kinase or p72 Syk or SYK or EC pipeline Target constitutes close to 26 molecules. (reportbuyer.com)
  • Additionally, the report provides an overview of key players involved in Tyrosine Protein Kinase JAK1 (Janus Kinase 1 or JAK1 or EC targeted therapeutics development and features dormant and discontinued projects. (globalmarketsdirect.com)
  • Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene. (wikipedia.org)
  • A cellular enzyme that transfers a phosphate group from ATP to a protein is known as a tyrosine kinase. (einpresswire.com)
  • Building a better understanding of the intracellular tyrosine kinase PTK6 - BRK by BRK. (springer.com)
  • The mammalian shc gene encodes two overlapping proteins of 46 and 52 kDa, each with a C-terminal Src homology 2 (SH2) domain and an N-terminal glycine/proline-rich sequence, that induce malignant transformation when overexpressed in mouse fibroblasts. (pnas.org)
  • A gene on chromosome 5q35.3 that encodes a tyrosine kinase receptor for vascular endothelial growth factors (VEGF) C and D, which appear to play a role in lymphangiogenesis and maintenance of the lymphatic endothelium. (thefreedictionary.com)
  • Antibodies specific for phosphatidylinositol-3 kinase alpha and phospholipase C-gamma 1 had no effect. (sciencemag.org)
  • These non-receptor cytoplasmic tyrosine kinases share a characteristic dual SH2 domain separated by a linker domain. (wikipedia.org)
  • MBP, a functionally important structural protein of myelin, is localized at opposing cytoplasmic faces of the myelin lamellae, which form the major dense line in electron micrographs ( Lemke, 1988 ). (jneurosci.org)
  • This allows tyrosine in the cytoplasmic portion of each receptor monomer to be transphosphorylated by its chaperone to propagate signals through the plasma membrane. (creativebiomart.net)
  • Immunoprecipitation of the p110 catalytic subunit of the phosphatidylinositol 3-kinase co-immunoprecipitated p85 in control lysates. (nih.gov)
  • Estrogen-independent and tamoxifen-resistant tumors often have increased levels of the ErbB family of receptor tyrosine kinases. (aacrjournals.org)
  • Chemotherapeutic vandetanib bound to its main target Protein Tyrosine Kinase 6 (PTK6) in purple, which is involved in many cancers including gastrointestinal tumors and ovarian cancers. (eurekalert.org)
  • By modeling vandetanib and PTK6 complex, researchers at LSU found that the KRAS protein to also contain a similar drug-binding site and therefore to be a good match for the same drug. (eurekalert.org)
  • To assess the physiological role of tyrosine nitration, it is crucial to identify the proteins that become nitrated. (nih.gov)
  • Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. (rcsb.org)
  • p46shc, p52shc, and an additional 66-kDa shc gene product become highly tyrosine phosphorylated in Rat-2 cells transformed by the v-src or v-fps oncogene. (pnas.org)
  • Abnormal expression of HER2 protein is thought to result in excess growth stimulation, converting HER2 into an oncogene . (ganfyd.org)
  • Ninety unique kinase genes can be identified in the human genome, along with five pseudogenes. (nih.gov)
  • Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. (creativebiomart.net)
  • To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. (reportlinker.com)
  • This progress had led to the development of small molecules that specifically inhibit the abnormally activated kinase. (haematologica.org)
  • In some cases, highly potent therapies that inhibit (red) the altered protein kinase have resulted in robust clinical outcomes. (asm.org)
  • Recently, treatment with bromodomain and extraterminal protein antagonist (BA) such as JQ1 has been shown to inhibit growth and induce apoptosis of human acute myelogenous leukemia (AML) cells, including those expressing FLT3-ITD. (aacrjournals.org)
  • 1999) Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells. (acris-antibodies.com)
  • In contrast, most transmembrane proteins (with a few exceptions) are excluded from the GEMs ( 4 )( 5 ). (rupress.org)
  • Without Syk, the protein it makes, and genetic disruption in a panel of 55 genes thought also to be controlled by Syk, breast ductal carcinoma in situ (breast DCIS, which can become invasive), it is believed that the cancer has a markedly increased tendency to invade and metastasize. (wikipedia.org)
  • A search of the human genome for tyrosine kinase coding elements identified several novel genes and enabled the creation of a nonredundant catalog of tyrosine kinase genes. (nih.gov)
  • Our microplate readers answer your questions on nucleic acids: concentration, interaction with other nucleic acids or proteins, single nucleotide polymorphisms and expression of genes. (bmglabtech.com)
  • Conclusion: Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. (uni-wuerzburg.de)
  • Met receptor tyrosine kinase: enhanced signaling through adapter proteins. (nih.gov)
  • The multisubstrate docking site mediates the binding of several adapter proteins such as Grb2, SHC, Crk/CRKL, and the large adapter protein Gab1. (nih.gov)
  • These adapter proteins in turn recruit several signal transducing proteins to form an intricate signaling complex. (nih.gov)
  • Plays a role in neural processes by phosphorylating DPYSL2 , a multifunctional adapter protein within the central nervous system, ARHGAP32 , a regulator for Rho family GTPases implicated in various neural functions, and SNCA , a small pre-synaptic protein. (rcsb.org)
  • The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. (reportbuyer.com)
  • When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the flexible linker domain and thereby keeps the inactive unit tightly bound. (wikipedia.org)
  • Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity). (rcsb.org)
  • Interacts with KDR (tyrosine phosphorylated). (rcsb.org)
  • Interacts (via its SH3 domain) with HEV ORF3 protein. (rcsb.org)
  • The HER2 protein , also known amongst other names as, ErbB2 or neu, and coded for by the ERBB2 gene at 17q12 derives its name from human epidermal growth factor receptor 2 , indicating its similarity to epidermal growth factor receptor (EGFR). (ganfyd.org)
  • Pfleger and Eidne, 2006 ) and developed new whole-cell receptor tyrosine kinase assays, which enabled us to monitor in living cells the ligand-induced recruitment of downstream effector proteins to various members of the RTK superfamily. (aspetjournals.org)
  • protein tyrosine kinase 6) is a soluble tyrosine kinase that was cloned from a metastatic breast tumor and found to be overexpressed in a majority of breast tumors. (aacrjournals.org)
  • A family of non-receptor, PROLINE-rich protein-tyrosine kinases. (umassmed.edu)
  • 2001) TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. (acris-antibodies.com)
  • Several Brk substrates and interacting proteins have been identified ( 8 ). (aacrjournals.org)
  • Recently, the Sam68-like proteins, SLM-1 and SLM-2, were identified as Brk substrates ( 9 ). (aacrjournals.org)
  • CK2 is a pleiotropic and constitutively active serine/threonine protein kinase composed of two catalytic (α and/or α′) and two regulatory β-subunits, whose mechanism of modulation is still obscure. (biochemj.org)
  • Tyrosine-protein kinase BLK, also known as B lymphocyte kinase, is a non-receptor tyrosine kinase that in humans is encoded by the BLK gene. (wikipedia.org)
  • PTP1B, protein tyrosine phosphatase 1B. (asm.org)
  • These results suggest that OVA-induced vasocontraction is mediated by the Rho-kinase-dependent inactivation of myosin light chain phosphatase via signaling downstream of Src-induced transactivation of EGFR. (ahajournals.org)