The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
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.
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 enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Agents that inhibit PROTEIN KINASES.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
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.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
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.
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 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 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.
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 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.
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 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.
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.
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.
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.
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.
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.
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.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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).
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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).
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.
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.
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.
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.
The rate dynamics in chemical or physical systems.
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.
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.
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.
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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 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.
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.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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 ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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 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.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Proteins prepared by recombinant DNA technology.
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.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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 group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
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.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
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.
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.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
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.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
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
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 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.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
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.
A cell line derived from cultured tumor cells.
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.
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 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.
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.
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.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
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.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
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.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
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.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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 multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Elements of limited time intervals, contributing to particular results or situations.
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.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
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.
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.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
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 serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
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.
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.
A group of phenyl benzopyrans named for having structures like FLAVONES.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
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 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 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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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 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)
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
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)
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC
The phosphoric acid ester of serine.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
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.
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.
A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.
An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
An enzyme that catalyzes the phosphorylation of the guanidine nitrogen of arginine in the presence of ATP and a divalent cation with formation of phosphorylarginine and ADP. EC
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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.
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.
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.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.
Adherence of cells to surfaces or to other cells.
The sum of the weight of all the atoms in a molecule.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A pyridoxal-phosphate protein that catalyzes the conversion of L-tyrosine to tyramine and carbon dioxide. The bacterial enzyme also acts on 3-hydroxytyrosine and, more slowly, on 3-hydroxyphenylalanine. (From Enzyme Nomenclature, 1992) EC
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.
Serine protein kinases involved in the regulation of ACTIN polymerization and MICROTUBULE disassembly. Their activity is regulated by phosphorylation of a threonine residue within the activation loop by intracellular signaling kinases such as P21-ACTIVATED KINASES and by RHO KINASE.
An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC
A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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 CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
An enzyme that catalyzes the cleavage of tyrosine to phenol, pyruvate, and ammonia. It is a pyridoxal phosphate protein. The enzyme also forms pyruvate from D-tyrosine, L-cysteine, S-methyl-L-cysteine, L-serine, and D-serine, although at a slower rate. EC
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.
Tyrosine kinase inhibitors[edit]. Crystal structure of Abl kinase domain (blue) in complex with 2nd generation tyrosine kinase ... a tyrosine kinase, and the BCR-Abl transcript is also translated into a tyrosine kinase containing domains from both the BCR ... "The Tyrosine Kinase c-Abl Responds to DNA Damage by Activating the Homeodomain-interacting Protein Kinase 2". Journal of ... Bandyopadhyay, G (2004). "Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase- ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Protein kinase *Tyrosine kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate ... "Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in atherosclerosis". Antioxidants & ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Protein kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... or tyrosine.[23] ... As a consequence, if two protein kinase inhibitors both bind in ... For example, some protein kinase inhibitors have chemical structures that are similar to adenosine triphosphate, one of the ... Bogoyevitch, MA; Barr, RK; Ketterman, AJ (2005). "Peptide inhibitors of protein kinases-discovery, characterisation and use". ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Tyrosine-kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Erlotinib ...
... kinases. Afatinib is not only active against EGFR mutations targeted by first generation tyrosine-kinase inhibitors (TKIs) like ... 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] ... Like lapatinib and neratinib, afatinib is a protein kinase inhibitor that also irreversibly inhibits human epidermal growth ...
The ligands interact with the two tyrosine kinase receptor monomers, PDGFRα (PDGFRA) and -Rβ (PDGFRB).[6] The PDGF family also ... 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.. ... "Embryonic mesoderm cells spread in response to platelet-derived growth factor and signaling by phosphatidylinositol 3-kinase" ...
See also: Discovery and development of Bcr-Abl tyrosine kinase inhibitors. Nilotinib was developed by Novartis.[3] It was ... Structurally related to imatinib,[18] It is 10-30 fold more potent than imatinib in inhibiting Bcr-Abl tyrosine kinase activity ... 2010). "Extended kinase profile and properties of the protein kinase inhibitor nilotinib". Biochimica et Biophysica Acta (BBA ... Breccia, M.; Alimena, G. (2010). "Nilotinib: a second-generation tyrosine kinase inhibitor for chronic myeloid leukemia". ...
cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine kinase activity. • ... protein kinase inhibitor activity. • protein kinase binding. • macromolecular complex binding. Cellular component. • cytoplasm ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin- ...
... especially those associated with receptor tyrosine kinases) is known as targeted therapy. ... Zhang J, Yang PL, Gray NS (Jan 2009). "Targeting cancer with small molecule kinase inhibitors". Nature Reviews. Cancer. 9 (1): ...
... a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): 949-57. doi:10.1083/jcb. ... "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha- ... "p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha- ... Takahashi K, Suzuki K, Tsukatani Y (July 1997). "Induction of tyrosine phosphorylation and association of beta-catenin with EGF ...
JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial ... As with other ATP competitive small molecule tyrosine kinase inhibitors, such as imatinib (Gleevec) in CML, patients rapidly ... Raymond E, Faivre S, Armand J (2000). "Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy". ... It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ...
protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... transmembrane receptor protein tyrosine kinase activity. • receptor tyrosine kinase. • transmembrane signaling receptor ... Within the cytoplasmic tyrosine kinase domain, there are 16 tyrosines (Tyrs) in RET9 and 18 in RET51. Tyr1090 and Tyr1096 are ... triggering trans-autophosphorylation of specific tyrosine residues within the tyrosine kinase domain of each RET molecule. ...
The active sites of tyrosine kinases each have a binding site for ATP. The enzymatic activity catalyzed by a tyrosine kinase is ... Some tumor cells, however, have a dependence on bcr-abl.[28] Inhibition of the bcr-abl tyrosine kinase also stimulates its ... Schiffer CA (July 2007). "BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia". N. Engl. J. Med. 357 (3): 258- ... Imatinib is a 2-phenyl amino pyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase ...
Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ... receptor serine/threonine kinase binding. • peroxisome proliferator activated receptor binding. • ubiquitin binding. ... This loop can be interfered with by kinases and genes like p14arf when p53 activation signals, including DNA damage, are high. ... "Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation". The EMBO Journal. 21 (14): 3715-27. doi:10.1093/ ...
Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ...
Tyrosine kinase inhibitors ("-nib"). Receptor tyrosine kinase. *ErbB: HER1/EGFR (Brigatinib. *Dacomitinib ... "Analplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer". UpToDate. Wolters Kluwer. Retrieved 30 ... "Anapestic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer". UpToDate. Wolters Kluwer. Retrieved 30 ... Ceritinib is an anaplastic lymphoma kinase (ALK)-positive inhibitor primarily used for the treatment of metastatic NSCLC.[4] ...
"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ... Gupta S, Davis RJ (October 1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Letters. 353 (3): 281 ... Iijima S, Teraoka H, Date T, Tsukada K (June 1992). "DNA-activated protein kinase in Raji Burkitt's lymphoma cells. ...
... and RET tyrosine kinases. RET tyrosine kinases; it weakly inhibits VEGFR-3.[5][9] ... an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases". Cancer Research. 62 ( ... and the RET-tyrosine kinase.[3][4] The drug was developed by AstraZeneca[1] and later on Sanofi.[citation needed] ... "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors". Drug Metabol Drug Interact. 0 (4): 249-59. doi:10.1515/dmdi ...
tyrosine kinase inhibitors (TKI's):[9] *erlotinib (Tarceva)[10][unreliable medical source?]. *gefitinib (Iressa)[11][unreliable ... Ansari J, Palmer DH, Rea DW, Hussain SA (June 2009). "Role of tyrosine kinase inhibitors in lung cancer". Anti-Cancer Agents in ... "The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies". ... "Morphologic features of adenocarcinoma of the lung predictive of response to the epidermal growth factor receptor kinase ...
Tyrosine kinase inhibitors (TKI) *Midostaurin. TKI acting on many different tyrosine kinases, approved by FDA and EMA for ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase". ... 1-phosphatidylinositol-3-kinase activity. • phosphatidylinositol-4,5-bisphosphate 3-kinase activity. • kinase activity. • ... protein kinase activator activity. • 1-phosphatidylinositol-4-phosphate 3-kinase activity. • protein serine/threonine kinase ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... This enzyme is also called galacturonokinase (phosphorylating) D-galacturonic acid kinase. This enzyme participates in ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ...
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 ... "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.". Nat. Biotechnol. 23 (1): 94-101. PMID 15592455. doi: ...
Other kinase/phosphatase. Tyrosine kinase. *BTK *X-linked agammaglobulinemia. *ZAP70 *ZAP70 deficiency ... RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity ... Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase ... RSK2 is a downstream component of the MAPK (mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 ...
Bcr-Abl tyrosine-kinase inhibitors. *Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor ...
... binding to cAMP-dependent protein kinase (PKA).[111] ... Substrates→Products: Tyrosine→L-DOPA (levodopa). *Inhibitors: 2 ...
"Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired ...
1992). "The lymphocyte-specific tyrosine protein kinase p56lck is endocytosed in Jurkat cells stimulated via CD2.". J. Immunol. ... Regulation by the CD45 tyrosine phosphatase.". J. Immunol. 145 (8): 2448-54. PMID 1976695.. ... Samelson LE, Fletcher MC, Ledbetter JA, June CH (1990). "Activation of tyrosine phosphorylation in human T cells via the CD2 ... to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation pathways dependent on protein kinase C and ...
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 ... Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD (Jan 2005). "Sterile 20 kinase phosphorylates histone H2B at serine 10 ... SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ...
Type 3: Kinase-linked and related receptors (see "Receptor tyrosine kinase" and "Enzyme-linked receptor") - They are composed ...
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 ... 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), ... "Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas". Journal of ...
Thakker DR, Standifer KM (2003). „Orphanin FQ/nociceptin blocks chronic morphine-induced tyrosine hydroxylase upregulation.". ... FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein kinase C: a ...
"Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3". ...
"Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias". Oncogene ... "Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase". J. Biol. Chem. 275 (34): ...
A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in people with advanced ...
2000). "The protein tyrosine kinase family of the human genome". Oncogene 19 (49): 5548-5557. PMID 11114734. doi:10.1038/sj.onc ... Zwick, E. Bange, J. Ullrich, A. (2001). "Receptor tyrosine kinase signalling as a target for cancer intervention strategies". ...
tyrosine 3-monooxygenase) kinase (EC *STK4. Myosin-heavy-chain kinase (EC *Aurora kinase *Aurora A kinase ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... Dephospho-(reductase kinase) kinase (EC *AMP-activated protein kinase α *PRKAA1 ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
... and the Fyn protein-tyrosine kinase". Molecular Biology Reports. 26 (3): 173-7. doi:10.1023/A:1006954206151. PMID 10532312.. ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ... protein kinase binding. • small GTPase binding. • Rac GTPase binding. Cellular component. • cytoplasm. • cell-cell junction. • ... Wu Y, Spencer SD, Lasky LA (March 1998). "Tyrosine phosphorylation regulates the SH3-mediated binding of the Wiskott-Aldrich ...
positive regulation of peptidyl-tyrosine phosphorylation. • positive regulation of protein tyrosine kinase activity. • positive ... activation of protein kinase activity. • calcium-mediated signaling using intracellular calcium source. • negative regulation ... The PrP-activated signal transduction pathway is associated with axon and dendritic outgrowth with a series of kinases.[25][46] ... is pivotal in memory processing and is likely modulated by the kinases PKA and ERK1/2.[35][36] ...
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. ... "Tyrosine phosphorylation of Crk-associated substrates by focal adhesion kinase. A putative mechanism for the integrin-mediated ... These include association with FAK and Src family kinases at focal adhesions to transmit integrin-initiated signals to ...
Copurification of tyrosine hydroxylase from rat pheochromocytoma by protein kinase". C. R. Acad. Sci. III. 302: 435-438. PMID ... Goodwill, K.E., Sabatier, C., Marks, C., Raag, R., Fitzpatrick, P.F. and Stevens, R.C. (1997). „Crystal structure of tyrosine ... Ikeda, M., Levitt, M. and Udenfriend, S. (1967). „Phenylalanine as substrate and inhibitor of tyrosine hydroxylase". Arch. ... Nagatsu, T., Levitt, M. and Udenfriend, S. (1964). „Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis". J. ...
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 ... CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ...
protein serine/threonine kinase activator activity. • receptor ligand activity. Cellular component. • extracellular region. • ... positive regulation of peptidyl-tyrosine phosphorylation. • striated muscle cell differentiation. • regulation of muscle cell ... positive regulation of protein kinase B signaling. • regulation of transcription, DNA-templated. • ossification. • platelet ... positive regulation of protein serine/threonine kinase activity. • carbohydrate metabolic process. • regulation of receptor ...
stress-activated protein kinase signaling cascade. • cellular response to peptide. • daunorubicin metabolic process. • ... 2acu: TYROSINE-48 IS THE PROTON DONOR AND HISTIDINE-110 DIRECTS SUBSTRATE STEREOCHEMICAL SELECTIVITY IN THE REDUCTION REACTION ... "Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C δ in a mouse ...
... 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 ...
proved that repeated exposure of GHB to MAP kinase affected myelin expression. This is a critical finding since myelin is the ... Tyrosine→Melanin. *Albinism: Ocular albinism (1). *Oculocutaneous albinism (Hermansky-Pudlak syndrome). *Waardenburg syndrome ... MAP kinase is imperative for numerous physiological changes including regulation of cell division and differentiation, thus, ... In terms of intracellular signaling, GHB inhibits mitogen activated protein (MAP) kinase action via the GABAB receptor ...
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 ...
Brutons tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is an enzyme that in humans is ... non-membrane spanning protein tyrosine kinase activity. • ATP binding. • protein binding. • protein tyrosine kinase activity. ... "Brutons tyrosine kinase (Btk) associates with protein kinase C mu". FEBS Lett. 461 (1-2): 68-72. doi:10.1016/S0014-5793(99) ... Brutons tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.[5] ...
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes ... Crystal structure of the second generation Bcr-Abl tyrosine-kinase inhibitor nilotinib (red) in complex with an Abl kinase ... Levitzki A, Mishani E (2006). "Tyrphostins and other tyrosine kinase inhibitors". Annu Rev Biochem. 75: 93-109. doi:10.1146/ ... It was further shown that in spite of the conservation of the tyrosine-kinase domains one can design and synthesize tyrphostins ...
... tyrosine kinase inhibitor (CHEBI:38637). EC (receptor protein-tyrosine kinase) inhibitor (CHEBI:62434) is a tyrosine ... 1-NA-PP1 (CHEBI:52310) has role tyrosine kinase inhibitor (CHEBI:38637). 1-NM-PP1 (CHEBI:52309) has role tyrosine kinase ... BE-23372M (CHEBI:65473) has role tyrosine kinase inhibitor (CHEBI:38637). biochanin A (CHEBI:17574) has role tyrosine kinase ... bosutinib hydrate (CHEBI:68533) has role tyrosine kinase inhibitor (CHEBI:38637). butein (CHEBI:3237) has role tyrosine kinase ...
Tyrosine-protein kinase, non-receptor Jak/Tyk2 (IPR016251)*Tyrosine-protein kinase, non-receptor Jak2 (IPR020693) ... GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity GO:0005524 ATP ...
Syk Kinase. We are also actively investigating the regulation of Syk tyrosine kinase binding to membrane immune receptors and ... "Substrate recognition by the Lyn protein-tyrosine kinase. NMR structure of the immunoreceptor tyrosine-based activation motif ... Tyrosine Kinases. The transduction of extracellular signals across the membrane to initiate complex cascades of molecular ... The molecular basis of phospho-tyrosyl-regulation of Src-family and Syk-family protein tyrosine kinases in signaling pathways ...
... 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, ... Tyrosine kinases can be categorized as receptor type or non-receptor type. Receptor type tyrosine kinases have an extracellular ... For example, the Bcr-Abl tyrosine kinase is the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome ...
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 ...
Smart drugs: tyrosine kinase inhibitors in cancer therapy.. Shawver LK1, Slamon D, Ullrich A. ... Protein-Tyrosine Kinases/antagonists & inhibitors*. *Protein-Tyrosine Kinases/metabolism. *Receptor Protein-Tyrosine Kinases/ ...
Whereas KIT possesses inherent tyrosine kinase activity, Fc epsilon RI requires the recruitment of Src family tyrosine kinases ... The signaling pathways propagated by these tyrosine kinases can be further upregulated by the Tec kinase Brutons tyrosine ... Basic structures of the tyrosine kinase, CSK, and the tyrosine phosphatases SHP1, SHP2, and CD45 ... The tyrosine kinase network regulating mast cell activation.. Gilfillan AM1, Rivera J. ...
... Aafaque Ahmad Khan,1,2 Varot K. Sandhya,1 Priyata Singh,3 Deepak ... Aafaque Ahmad Khan, Varot K. Sandhya, Priyata Singh, et al., "Signaling Network Map of Endothelial TEK Tyrosine Kinase," ...
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 ... Kinase, Transferase, Tyrosine-protein kinaseUniRule annotation. Automatic assertion according to rulesi ... PS00107 PROTEIN_KINASE_ATP, 1 hit. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 hit. PS50001 SH2, 1 hit ...
... 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, ...
Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. P M Guy, J V Platko, L C Cantley, R A Cerione, ... Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. P M Guy, J V Platko, L C Cantley, R A Cerione, ... suggesting that these residues are necessary for kinase activity. In p180erbB3, a receptor tyrosine kinase belonging to the ... Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. P M Guy, J V Platko, L C Cantley, R A Cerione, ...
An isolated nucleic acid molecule encoding a novel human receptor type tyrosine kinase gene, KDR, is disclosed. The isolation ... assays employing these receptor type tyrosine kinase genes, cells expressing these receptor type tyrosine kinase genes, and ... assays employing these receptor type tyrosine kinase genes, cells expressing these receptor type tyrosine kinase genes, and ... because the sKDR forms are devoid of an intracellular tyrosine kinase region, prevent receptor tyrosine kinase domain ...
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. Tyrosine ... A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. Tyrosine ... Approximately 2000 kinases are known and more than 90 Protein Tyrosine Kinases (PTKs) have been found in the human genome. They ... Oncogenic Fusion Tyrosine Kinases As Molecular Targets for Anti-Cancer Therapy. Anti-Cancer Agents in Medicinal Chemistry, 2007 ...
The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and ... particularly those drugs that inhibit the activity of tyrosine kinases, has become a remarkable progress in the treatment of ... The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and ... Here we summarize what is known up to date about the cardiotoxicity of drugs targeting the tyrosine kinases. Being aware of the ...
Tyrosine kinases,state=autocollapse}}. *shows the template collapsed to the title bar if there is a {{navbar}}. , a {{sidebar}} ... Tyrosine kinases,state=collapsed}}. to show the template collapsed, i.e., hidden apart from its title bar ... Tyrosine kinases,state=expanded}}. to show the template expanded, i.e., fully visible ... Retrieved from "" ...
Brutons tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase critical for B cell signal transduction. While it has been ... 1997) Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity. J Biol Chem ... The structures of Tec kinases resembles that of Src and Abl families of cytoplamsmic tyrosine kinases in that they contain the ... 1B) (27⇓⇓⇓⇓-32). A feature that distinguishes Btk and other Tec family members from other cytoplasmic tyrosine kinases is the ...
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 ...
... 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 ...
SYK(SYKKD). SYK is a member of the SYK family of family of tyrosine protein kinases, a family of cytoplasmic tyrosine kinases ... The present invention concerns crystalline forms of polypeptides that correspond to the kinase domain of spleen tyrosine kinase ... 0317] The structure in both cases was that of a monomeric kinase domain with a subdomain structure typical for kinases, i.e. ... 0048] The target may, for example, be another kinase. The target may be another SYK family kinase, for example, ZAP70. ...
Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. FYN and NOX4 ... Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative ...
... Receptor tyrosine kinases (RTK)s are the high affinity cell surface receptors for many polypeptide ... Abelson leukemia virus protein - c-Kit - C-MET - Flt3 - Janus kinase (Janus kinase 1, Janus kinase 2, Janus kinase 3, Tyrosine ... Of the ninety unique tyrosine kinase genes idenitified in the human genome, 58 encode receptor tyrosine kinase proteins.[1] ... Kinase enzymes that specifically phosphorylate tyrosine amino acids are termed tyrosine kinases. ...
... Opportunities and Market Forecast to 2026 - published on openPR ... Tyrosine Kinase Inhibitors. • Vascular Endothelial Growth Factor (VEGFR) Tyrosine Kinase Inhibitors. Global Tyrosine Kinase ... Tyrosine Kinase Inhibitors - Pipeline Insights 2017 The "Tyrosine kinase Inhibitors-Pipeline Insights 2017″ report provides a ... Tyrosine Kinase Inhibitors - Pipeline Insights 2017 The "Tyrosine kinase Inhibitors-Pipeline Insights 2017″ report provides a ...
Tyrosine Phosphatase Inhibitors, Tyrosine Phosphatase Substrates, Tyrosine Phosphatases ... Browse Sigma-Aldrichs Tyrosine Phosphatase Biology to find products in Tyrosine Phosphatase Assays, ... USA Home > Product Directory > Cell Biology > Cell Signaling and Neuroscience > Kinase/Phosphatase Biology > Tyrosine ...
Src tyrosine kinase is a critical signal transducer that modulates a wide variety of cellular functions. Misregulation of Src ... Recently, it was discovered that G alpha s and G alpha i could directly stimulate Src family tyrosine kinase activity. This ... Novel regulation and function of Src tyrosine kinase.. Ma Y.C., Huang X.Y. ... novel regulation of Src tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling ...
... a member of the receptor tyrosine kinase (RTK) superfamily, is essential for development of the enteric nervous system and ... GDNF signalling through the Ret receptor tyrosine kinase Nature. 1996 Jun 27;381(6585):789-93. doi: 10.1038/381789a0. ... a member of the receptor tyrosine kinase (RTK) superfamily, is essential for development of the enteric nervous system and ...
Tyrosine Kinases RT2 Profiler PCR Array The Rat Tyrosine Kinases RT2 Profiler PCR Array profiles the expression of 84 receptor ... Tyrosine Kinases RT2 Profiler PCR Array The Human Tyrosine Kinases RT2 Profiler PCR Array profiles the expression of 84 ... Tyrosine Kinases RT2 Profiler PCR Array The Mouse Tyrosine Kinases RT2 Profiler PCR Array profiles the expression of 84 ... Receptor Tyrosine Kinase (Panel II) qBiomarker Somatic Mutation PCR Array The Human Receptor Tyrosine Kinase (RTK) Pathways ...
HER kinase axis receptor dimer partner switching occurs in response to EGFR tyrosine kinase inhibition despite failure to block ... Reduced proteolytic shedding of receptor tyrosine kinases is a post-translational mechanism of kinase inhibitor resistance. ... Endocytosis of receptor tyrosine kinases. Cold Spring Harb. Perspect. Biol. 5:a017459-a017459, 2013.CrossRefGoogle Scholar ... Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J. Clin. Oncol. 31:1070-1080, 2013.CrossRefGoogle ...
  • It is based, at least in part, on the discovery that the trkB proto-oncogene encodes a tyrosine kinase receptor that may serve as a functional binding protein for BDNF and NT-3. (
  • We are also actively investigating the regulation of Syk tyrosine kinase binding to membrane immune receptors and other signaling proteins. (
  • However, p180erbB3 is capable of binding the ATP analog 5'-p-fluorosulfonylbenzoyladenosine, indicating that the lack of observed kinase activity is probably not due to nonfunctional or denatured receptors expressed by the insect cells. (
  • Receptor tyrosine kinases (RTK)s are the high affinity cell surface receptors for many polypeptide growth factors , cytokines and hormones . (
  • The intracellular C-terminal region comprises domains responsible for the kinase activity of these receptors. (
  • Receptor tyrosine kinases are a large family of cell-surface receptors that respond to a variety of intercellular signals, including insulin, growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), and molecules involved in neuronal guidance. (
  • Ligand binding stimulates the tyrosine kinase activity of the receptors, leading to recruitment of enzymes and adapter proteins that activate intracellular signaling pathways that control cell proliferation, differentiation, and numerous other biological processes. (
  • c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. (
  • In this review, the importance of glioblastoma multiforme in signaling pathways initiated by extracellular tyrosine kinase receptors such as EGFR, PDGFR and IGF-1R will be discussed. (
  • 1994). Following ligand binding to the extracellular domain, the TYRO3 receptors dimerize and autophosphorylation of the tyrosine kinase domain occurs. (
  • In animal, receptor tyrosine kinases is the membrane receptors that recognize hydrophilic ligands. (
  • Signaling by receptor tyrosine kinases (RTKs) involves ligand-induced dimerization of receptors within the plasma membrane, triggering subsequent downstream signaling events. (
  • The FLT3 ligand is a hematopoietic growth factor that stimulates cells via a set of structurally related tyrosine kinase receptors. (
  • Lyn-deficient B cells fail to recruit protein tyrosine phosphatases to the plasma membrane due to defects in phosphorylation of inhibitory receptors ( 16 - 19 , 22 ). (
  • We identified TYRO3 and AXL , belonging to the TAM family (Tyro3, Axl, and Mer) of tyrosine kinase receptors ( 7, 8 ). (
  • Dasatinib is an inhibitor of tyrosine kinases receptors so it acts as anti-RTKs. (
  • The structural investigation revealed that Dasatinib IC50 for SRC tyrosine kinase receptors and ABL it is 0.55 and 3nm respectively [2]. (
  • Expression of tyrosine kinase receptors in lung carcinoids. (
  • The molecular basis of phospho-tyrosyl-regulation of Src-family and Syk-family protein tyrosine kinases in signaling pathways is a current focus of the lab. (
  • Tyrosine kinases and their downstream signaling pathways are involved in many basic biological processes, such as growth, proliferation, and differentiation. (
  • The Human Receptor Tyrosine Kinase (RTK) Pathways qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid and accurate profiling of the somatic mutation status for. (
  • Tyrosine kinases function in a variety of processes, pathways, and actions, and are responsible for key events in the body. (
  • Lyn and Src family tyrosine kinases in general have been known to function in signal transduction pathways. (
  • Fibroblast growth receptor 1, platelet-derived growth factor receptor-α, and epidermal growth factor receptor are all potential entry points to the phosphatidylinositol 3-kinase and mitogen-activated protein kinase intracellular signaling pathways already known to be important for neoplasia. (
  • These adaptor proteins link RTK activation to downstream signal transduction pathways, such as the MAP kinase signalling cascade . (
  • This engagement transduces activating signal pathways such as phospholipase C-(PLC-) γ and phosphatidylinositol-3 kinase (PI3 K) [ 2 ] and triggers activation of intrinsic glomerular cells or infiltrating leukocytes to release many inflammatory mediators, such as complements, vasoactive substances, cytokines, and coagulation factors [ 1 , 3 , 4 ]. (
  • Thus, inhibitors that block the activity of tyrosine kinases and the signaling pathways they activate may provide a useful basis for drug development. (
  • 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). (
  • General receptor tyrosine kinase (RTK) endocytosis and recycling pathways. (
  • Tyrosine kinases constitute a large family of evolutionarily conserved enzymes that activate/deactivate a number of different metabolic pathways by catalyzing the phosphorylation of specific tyrosine residues on key effector proteins. (
  • The Lyn tyrosine kinase is involved in both positive and inhibitory signaling pathways in B lymphocytes ( 13 ). (
  • Having noted the effects of the absence of Lyn activity ( 24 ), we now ask what immunological consequences flow from the constitutive engagement of both stimulatory and inhibitory signaling pathways using a targeted gain-of-function Lyn tyrosine kinase mutant (Lyn up/up mice). (
  • To study the effectiveness of Dasatinib in prostate cancer it has shown to block a number of signaling pathways such as SFKs, Src kinases, Lyn and p130CAS by stopping them [8]. (
  • The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphorylate serine or threonine residues and can discriminate between the kinase domains of the EGFR and that of the insulin receptor . (
  • Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal)phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (
  • Kinases that phosphorylate serine and threonine residues, and3. (
  • Kinases with activity toward all three residues. (
  • 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. (
  • A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. (
  • Tyrosine kinases catalyze the phosphorylation of tyrosine residues in proteins. (
  • The phosphorylation of tyrosine residues in turn causes a change in the function of the protein that they are contained in. (
  • Phosphorylation at tyrosine residues controls a wide range of properties in proteins such as enzyme activity, subcellular localization, and interaction between molecules. (
  • proteins in the cytosol and proteins in the nucleus are phosphorylated at tyrosine residues during this process. (
  • Protein kinases share a number of highly conserved or invariant amino acid residues in their catalytic domains, suggesting that these residues are necessary for kinase activity. (
  • In p180erbB3, a receptor tyrosine kinase belonging to the epidermal growth factor (EGF) receptor subfamily, three of these residues are altered, suggesting that this protein might have an impaired protein tyrosine kinase activity. (
  • 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. (
  • The activated receptor as a result then becomes autophosphorylated on multiple specific intracellular tyrosine residues. (
  • The phosphorylation of specific tyrosine residues within the activated receptor creates binding sites for Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain containing proteins. (
  • Tyrosine kinases are enzymes capable of phosphorylating tyrosine residues within proteins. (
  • c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (
  • It phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs). (
  • 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. (
  • 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. (
  • Lyn's role in activation is mediated by the phosphorylation of tyrosine residues within immunoreceptor tyrosine-based activation motifs of proteins such as Igα, Igβ, and CD19, and the subsequent recruitment of enzymes such as Syk, phospholipase Cγ2 (PLCγ2), and phosphatidyl inositol-3 kinase ( 14 ). (
  • As a balance, there is suppression of B cell stimulation from Lyn-dependent phosphorylation of tyrosine residues within immunoreceptor tyrosine-based inhibitory motifs in proteins such as CD22, PIR-B, and FcγRIIb1, with the concomitant recruitment to the plasma membrane of phosphatases such as SHP-1 and SHIP-1 ( 15 - 21 ). (
  • Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. (
  • 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. (
  • QIAGEN provides a broad range of assay technologies for tyrosine kinase research that enable analysis of gene expression and regulation, epigenetic modification, and signal transduction pathway activation. (
  • Phosphorylation of proteins by kinases is an important mechanism for communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division. (
  • Furthermore, tyrosine kinases function in many signal transduction cascades wherein extracellular signals are transmitted through the cell membrane to the cytoplasm and often to the nucleus, where gene expression may be modified. (
  • The receptor tyrosine kinases function in transmembrane signaling, whereas tyrosine kinases within the cell function in signal transduction to the nucleus. (
  • P rotein kinases are key modulators of signal transduction and play essential roles in the regulation of cell cycle, cellular movement, apoptosis, and other processes that are fundamental to the development and progression of cancers ( 1 ). (
  • Phosphorylation of proteins by kinases is an important mechanism in signal transduction for regulation of enzyme activity. (
  • 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. (
  • A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth. (
  • The two nonreceptor tyrosine kinases, spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk), are primarily expressed by hematopoietic cells, and participate in B-cell-receptor- and Fc-receptor-mediated activation. (
  • Rational design of highly selective spleen tyrosine kinase inhibitors. (
  • 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, and SLE. (
  • We report the structure-guided identification of three series of selective spleen tyrosine kinase inhibitors that support our hypothesis, and offer useful guidance to other researchers in the field. (
  • 27 Spleen tyrosine Kinase (SYK) ELISA Kits von 5 Herstellern verfügbar auf (
  • It has been reported that spleen tyrosine kinase (Syk) regulates actin cytoskeleton and that it may interact with TLR4. (
  • Recent structural studies of receptor tyrosine kinases (RTKs) have revealed unexpected diversity in the mechanisms of their activation by growth factor ligands. (
  • Human receptor tyrosine kinases (RTKs) contain 20 subfamilies, shown here schematically with the family members listed beneath each receptor. (
  • Top: In general, receptor tyrosine kinases (RTKs) associate into dimers when ligand (red) binds to their extracellular regions. (
  • Dimerization of the extracellular regions of RTKs activates the intracellular tyrosine kinase domains (TKDs), which contain a C-lobe (light purple or yellow), N-lobe (dark purple or yellow in the inactive and active states), and an activation loop (dark purple or yellow in the inactive and active states, respectively). (
  • The protein tyrosine kinase superfamily includes roughly 60 receptor tyrosine kinases (RTKs) and about 30 intracellular tyrosine kinases. (
  • Upon activation, RTKs dimerize and autophosphorylate their intracellular domains, initiating downstream signaling that often includes non-receptor tyrosine kinases. (
  • At present, 58 receptor tyrosine kinases (RTKs) are known, grouped into 20 subfamilies. (
  • For instance, target and alternative receptor tyrosine kinases (RTKs) can exhibit enhanced activities via increased expression even in the absence of gene amplification, 4 , 10 , 35 , 46 , 49 including by means of modulated ligand binding and/or receptor oligomerization. (
  • however, drugs that target RTKs, known as tyrosine kinase inhibitors (TKIs) have not been effective in treating breast cancer. (
  • 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 . (
  • Among these, receptor tyrosine kinases (RTKs), such as vascular endothelial growth factor receptor-2 (VEGFR2) and fibroblast growth factor receptor-1 (FGFR1), are essential regulators of such essential EC activities as proliferation, migration, angiogenesis, and vascular permeability. (
  • Dasatinib BCR-ABL inhibitor also has been seen to inhibit various sorts of RTKs at different intensities for example for Src family (c-Kit, eph kinases, Src) was seen to be inhibited at different specificities [6]. (
  • Written and edited by experts in the field, Signaling by Receptor Tyrosine Kinases from Cold Spring Harbor Perspectives in Biology discusses the mechanisms underlying receptor tyrosine kinase signaling, including ligand processing, receptor dimerization, receptor trafficking, and the roles of adapters. (
  • Liu F, Zhuang S. Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis. (
  • It is now generally accepted that receptor tyrosine kinase signaling occurs intracellularly and on the plasma membrane, although many important details remain to be worked out. (
  • Endocytosis and subsequent intracellular trafficking spatiotemporally regulate receptor tyrosine kinase signaling, whereas signaling endosomes provide a platform for the compartmentalization of signaling events. (
  • Our results support the idea that the regulation of NMJ function by SKN-1 occurs via a complex organism-wide signaling network involving receptor tyrosine kinase signaling in multiple tissues. (
  • They are also called tyrphostins , the short name for " tyrosine phosphorylation inhibitor ", originally coined in a 1988 publication, [1] which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). (
  • It was further shown that in spite of the conservation of the tyrosine-kinase domains one can design and synthesize tyrphostins that discriminate between even closely related protein tyrosine kinases such as EGFR and its close relative HER2 . (
  • Receptor tyrosine kinases eg: EGFR, PDGFR, FGFR2. (
  • 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). (
  • 6 In particular, EGFR activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) 7 and AKT 8 signaling from EEA1-positive (early endosome antigen 1) early endosomes. (
  • The prevalence and characteristics of receptortyrosine-kinase (RTK) fusion as acquired resistance to EGFR tyrosine-kinase inhibitors (TKIs) are rarely investigated. (
  • The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR + mutations. (
  • To assess the physiological role of tyrosine nitration, it is crucial to identify the proteins that become nitrated. (
  • Therefore, we treated lysates from RAW 264.7 cells with 1 mM peroxynitrite and immunoprecipitated tyrosine nitrated proteins. (
  • Of the ninety unique tyrosine kinase genes idenitified in the human genome, 58 encode receptor tyrosine kinase proteins. (
  • This novel regulation of Src tyrosine kinase by G proteins provides insights into the adenylyl cyclase-independent signaling mechanisms involved in ligand-induced receptor desensitization, internalization and other physiological processes. (
  • The human TAM genes share similar genomic structures, and their resulting proteins share significant structural similarities, with greatest homology in the tyrosine kinase domain. (
  • As we know, kinases is the enzyme that phosphorylate proteins. (
  • The signal was transferred from the receptor into the cytoplasm via proteins that bind to phosphorylated tyrosines. (
  • In order to maximize the function of kinase cascades, a type of proteins, called scafford proteins, rearrange the kinase cascade into a protein complex. (
  • We report that exposure of microglia and THP1 monocytes to fibrillar Aβ led to time- and dose-dependent increases in protein tyrosine phosphorylation of a population of proteins similar to that elicited by classical immune stimuli such as immune complexes. (
  • Importantly, microglia that are in direct contact with senile plaques exhibit high levels of tyrosine-phosphorylated proteins ( Wood and Zinsmeister, 1991 ), suggesting sustained activation of intracellular signaling processes. (
  • The present invention provides methods for use of IL-21 in combination with a tyrosine kinase inhibitor (TKI) in treatment of diseases in which inhibition of phosphorylation via TK inhibition and modulation of immune function play a clinically beneficial role. (
  • The inhibition of NF-kappaB activation by PI3-kinase inhibitors was also observed in pervanadate-stimulated but not in LPS-stimulated cells. (
  • The alternative splice variant of protein tyrosine kinase 6 negatively regulates growth and enhances PTK6-mediated inhibition of β-catenin. (
  • A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. (
  • PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation. (
  • the transmembrane receptor-linked kinases. (
  • Lemur Tyrosine Kinase 2 (LMTK2) is a recently cloned transmembrane protein, actually a serine/threonine kinase named after the Madagascar primate lemur due to the long intracellular C-terminal tail. (
  • The TAM (Tyro3, Axl, MerTK) family of receptor tyrosine kinases (RTK) is defined by each member possessing an extracellular combination of two immunoglobulin-like domains and two fibronectin type III repeats, a transmembrane portion, and an intracellular region with intrinsic tyrosine kinase activity. (
  • Receptor tyrosine kinases is a transmembrane structure that anchors into the membrane. (
  • Disrupting intermolecular interactions between transmembrane domains is a potential method for attenuating signaling through receptor tyrosine kinases. (
  • KIT is a proto-oncogene encoding a transmembrane tyrosine kinase receptor for stem cell factor required for normal hematopoiesis, melangenesis and gametogenesis. (
  • Your search returned 81 c-mer proto-oncogene tyrosine kinase ELISA ELISA Kit across 15 suppliers. (
  • MERTK (cMER) is a tyrosine kinase proto-oncogene and is involved in the retinal pigment epithelium (RPE) phagocytosis pathway, which is implicated in human retinal disease. (
  • Numerous TKIs aiming at various tyrosine kinases have been generated by the originators of these compounds and proven to be effective anti- tumor agents and anti- leukemic agents. (
  • [11] Recently TKIs have been shown to deprive tyrosine kinases of access to the Cdc37 - Hsp90 molecular chaperone system on which they depend for their cellular stability, leading to their ubiquitylation and degradation. (
  • Pazopanib is a novel antiangiogenic inhibitor of tyrosine kinases (TKIs) with high activity against vascular endothelial growth factor receptor (VEGFR1-3), platelet-derived growth factor receptor (PDGFRα+β), and c-Kit. (
  • It is also showed that tyrosine kinases inhibitors (TKIs) have anti-fibrotic effects in basic research and clinical trials. (
  • A relatively new targeted chemotherapeutic treatment consists of a series of small molecules collectively known as tyrosine kinase inhibitors (TKIs). (
  • 7 , 8 Understanding of this critical mechanism led to the development of targeted therapies including the anti-VEGF antibody bevacizumab, and more recently, VEGF receptor tyrosine kinase inhibitors (VEGFR-TKIs), which are now used as standard of treatment for metastatic RCC (mRCC). (
  • Tyrosine kinases belong to a larger class of enzymes known as protein kinases which also attach phosphates to other amino acids such as serine and threonine. (
  • The enzymes fall into two broad classes, characterised with respect to substrate specificity: serine/threonine-specific, and tyrosine-specific (the subject of this article). (
  • Kinase is a large family of enzymes that are responsible for catalyzing the transfer of a phosphoryl group from a nucleoside triphosphate donor, such as ATP, to an acceptor molecule. (
  • Kinase enzymes that specifically phosphorylate tyrosine amino acids are termed tyrosine kinases . (
  • 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. (
  • Bruton's tyrosine kinase (abbreviated Btk or BTK ), also known as tyrosine-protein kinase BTK , is an enzyme that in humans is encoded by the BTK gene . (
  • Ibrutinib (PCI-32765), a selective Bruton's tyrosine kinase inhibitor. (
  • Bruton's tyrosine kinase was discovered in 1993 and is named for Ogden Bruton , who first described XLA in 1952. (
  • We investigated the effects of Bruton's tyrosine kinase (BTK) on CCRT-resistant OSCC tissues. (
  • The conformational activation of Src kinase must be carefully regulated in cells for proper function and to avoid disease. (
  • that is, how kinase interactions observed crystallographically and validated by mutagenesis can regulate activation is rationalized by the energetic profile from the transition pathway calculations. (
  • NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor. (
  • Strategies for inducing dimerization by ligand binding are surprisingly diverse, as are mechanisms that couple this event to activation of the intracellular tyrosine kinase domains. (
  • For example, the SRC-family kinase regulatory domain requires autophosphorylation for kinase domain activation, while most other intracellular tyrosine kinase families use different regulatory mechanisms. (
  • Dimerization leads to a rapid activation of the protein's cytoplasmic kinase domains, the first substrate for these domains being the receptor itself. (
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (
  • The activation of tyrosine kinases is the initial step in regulating a variety of cellular processes, including proliferation, differentiation, and inflammatory responses. (
  • Phosphoinositide 3-kinase activity leads to silica-induced NF-kappaB activation through interacting with tyrosine-phosphorylated IkappaB-alpha and contributing to tyrosine phosphorylation of p65 NF-kappaB. (
  • The role of the subunits of phosphoinositide (PI) 3-kinase in NF-kappaB activation in silica-stimulated RAW 264.7 cells was investigated. (
  • PI3-kinase specific inhibitors, such as wortmannin and LY294003, substantially blocked both silica-induced PI3-kinase and NF-kappaB activation. (
  • Antioxidants, such as superoxide dismutase (SOD), N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), blocked silica-induced PI3-kinase activation, suggesting that reactive oxygen species may be important regulatory molecules in NF-kappaB activation by mediating PI3-kinase activation. (
  • Our data suggest that p85 and p110 subunits of PI3-kinase play a role in NF-kappaB activation through interaction with tyrosine-phosphorylated kappaIB-alpha and contributing to tyrosine phosphorylation of p65 NF-kappaB. (
  • Breast tumor kinase (protein tyrosine kinase 6) regulates heregulin-induced activation of ERK5 and p38 MAP kinases in breast cancer cells. (
  • This results in defective inhibitory signaling and as a consequence, Lyn-deficient B cells are hyperresponsive to BCR stimulation and show enhanced proliferation, calcium flux, and activation of the mitogen-activated protein kinase pathway ( 15 - 19 , 23 ). (
  • Activation of the co-receptor complex transduces a signal, which in turn, stimulates tyrosine kinase activity in the intracellular domain. (
  • Taken together, these results suggest that Syk is a critical kinase in the mmLDL macrophage activation and that the mmLDL-induced cytoskeleton signaling. (
  • To examine the effect of tyrosine kinase activation on ACA, an epitope-tagged AC isoform VI (AC6) was constructed and transiently transfected in HEK 293 cells (HEK-AC6). (
  • Serine, tyrosine and threonine kinases are the three most common. (
  • We have found that, while the EGF receptor readily undergoes EGF-stimulated autophosphorylation and catalyzes the incorporation of phosphate into the model substrates (E4Y1)n (random 4:1 copolymer of glutamic acid and tyrosine) and GST-p85 (glutathione S-transferase fusion protein with the 85-kDa subunit of phosphatidylinositol 3-kinase), p180erbB3 autophosphorylation and substrate phosphorylation are at least 2 orders of magnitude less efficient. (
  • Immunoprecipitation of the p110 catalytic subunit of the phosphatidylinositol 3-kinase co-immunoprecipitated p85 in control lysates. (
  • Cell signaling by receptor tyrosine kinases. (
  • Here we report on the sequence analysis of members of the receptor tyrosine kinase (RTK) gene family in the genomes of glioblastoma brain tumors. (
  • i ) fibroblast growth receptor 1, including the first mutations in the kinase domain in this gene observed in any cancer, and ( ii ) a frameshift mutation in the platelet-derived growth factor receptor-α gene. (
  • An isolated nucleic acid molecule encoding a novel human receptor type tyrosine kinase gene, KDR, is disclosed. (
  • pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. (
  • It belongs to a family of Src family kinases and is similar to the v-Src (viral Src) gene of Rous sarcoma virus. (
  • 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. (
  • ALK (anaplastic lymphoma receptor tyrosine kinase) Hybridization with Vysis ALK Break Apart probe (Abbott Molecular, US) showing the gene at 2p23 (red-green or a fused yellow signal - Courtesy Adriana Zamecnikova. (
  • The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and trastuzumab, the humanized monoclonal antibody against the ERBB2 receptor tyrosine kinase, has proved to have a high efficacy in 25% of breast cancers. (
  • A new business intelligence report released by Up Market Research with title "Global Tyrosine Kinase Inhibitors Market Research Report 2019" that targets and provides comprehensive market analysis with future prospects to 2026. (
  • The global Tyrosine Kinase Inhibitors market will reach Volume Million USD in 2018 with CAGR xx% 2018-2025. (
  • These oncogenic processes make the tyrosine kinase superfamily members attractive drug targets, and there are several chemotherapeutics targeting tyrosine kinases already on the market (e.g., imatinib mesylate). (
  • It is now clear that tyrosine kinases represent attractive targets for therapeutic intervention in cancer. (
  • To find molecular targets, we have sequenced the coding exons for the kinase domains of 20 human receptor tyrosine kinase (RTK) genes in glioblastomas. (
  • Tyrosine kinase started to phosphorylate intracellular targets. (
  • In this study we identified the TYRO3 and AXL receptor tyrosine kinases as transcriptional targets of the chemokine CXCL12/SDF-1 in CXCR4-expressing thyroid cancer cells. (
  • Two closely spaced tyrosines regulate NFAT signaling in B cells via Syk association with Vav. (
  • Protein tyrosine kinases (PTKs) regulate cell proliferation, cell differentiation, and signaling processes in the cells of the immune system. (
  • The epidermal growth factor receptor is a receptor tyrosine kinases that signals in response to various growth factors. (
  • On the basis of these results, we propose that p180erbB3 possesses an impaired intrinsic tyrosine kinase activity. (
  • BCR-ABL Tyrosine Kinase Inhibitors eg: Imatinib Mesylate, Dasatinib, and Nilotinib.2. (
  • The purpose of this study is to evaluate the safety and efficacy of the tyrosine kinase inhibitor, imatinib mesylate (Gleevec ) in reducing peripheral blood eosinophilia in patients with the myeloid form of hypereosinophilic syndrome (HES). (
  • Non-receptor tyrosine kinases include a catalytic domain and a regulatory domain, which vary for each family. (
  • Imatinib (brand names Gleevec and Glivec) is a drug able to bind the catalytic cleft of these tyrosine kinases, inhibiting its activity. (
  • Identification of the murine ortholog, sik, in mouse intestinal cells was achieved by the generation of a library of kinase catalytic domains. (
  • Normally the level of cellular tyrosine kinase phosphorylation is tightly controlled by the antagonizing effect of tyrosine kinase and tyrosine phosphatases. (
  • An electrostatic network and long-range regulation of Src kinases. (
  • Studying tyrosine kinase expression and regulation in an experimental model system can yield new insights into their role in normal biological and pathophysiological processes. (
  • Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. (
  • 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. (
  • 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. (
  • Receptor tyrosine kinases are involved in regulation of key processes in endothelial biology, including proliferation, migration, and angiogenesis. (
  • We identified two receptor tyrosine kinases, EGL-15 (fibroblast growth factor receptor, FGFR) and DAF-2 (insulin-like peptide receptor), that are required for NMJ regulation in response to stress. (
  • Through double-mutant analysis, we found that EGL-15 functions downstream of, or parallel to, SKN-1 and SPHK-1 (sphingosine kinase), and that the EGL-15 ligand EGL-17 FGF and canonical EGL-15 effectors are required for oxidative stress-mediated regulation of NMJ function. (
  • In humans, there are 32 cytoplasmic protein tyrosine kinases ( EC (
  • In contrast to FGFRs 1-4 it lacks a cytoplasmic tyrosine kinase domain and one isoform, FGFR5γ, only contains the extracellular domains D1 and D2. (
  • Cytoplasmic protein tyrosine phosphatases such as SHP-1 also modulate BCR signaling ( 9 ) as exemplified by the severe B cell lymphopenia and autoantibody production of motheaten mice ( 10 ) that carry a debilitating mutation in SHP-1 ( 11 , 12 ). (
  • In every case, the result is a hyper-active kinase, that confers an aberrant, ligand-independent, non-regulated growth stimulus to the cancer cells. (
  • [6] These isoforms vary in their ligand binding properties and kinase domains, however all share a common extracellular region composed of three immunoglobulin (Ig) like domains (D1-D3), and thus belong to the immunoglobulin superfamily . (
  • The structure consists of ligand-binding domain in the outside and the kinase domain in the inside of the cell. (
  • AXL displayed high levels of tyrosine phosphorylation in most cancer cell lines due to constitutive expression of its ligand GAS6. (
  • The Breast tumor kinase Brk is a prototypical non-myristoylated, non-receptor tyrosine kinase. (
  • 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. (
  • Castro NE, Lange CA. Breast tumor kinase and extracellular-signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells. (
  • Lukong KE, Larocque D, Tyner AL, Richard S. Tyrosine phosphorylation of sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression. (
  • Breast tumor kinase (Brk/PTK6) plays a role in the differentiation of primary keratinocytes. (
  • Role of breast tumor kinase in the in vitro differentiation of HaCaT cell. (
  • Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. (
  • Recently, it was discovered that G alpha s and G alpha i could directly stimulate Src family tyrosine kinase activity. (
  • The Src-family tyrosine kinase Fyn is involved in the initial events of myelination. (
  • Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. (
  • Kinases that specifically phosphorylate tyrosine residues2. (
  • The first non-receptor tyrosine kinase identified was the v-src oncogenic protein. (
  • Tyrosine kinase activity in the nucleus involves cell-cycle control and properties of transcription factors. (
  • Fibroblasts - a type of cell that synthesizes the extracellular matrix and collagen and is involved in wound healing - that have been transformed by the polyomavirus possess higher tyrosine activity in the cellular matrix. (
  • Furthermore, tyrosine kinase activity has been determined to be correlated to cellular transformation. (
  • The development of the so-called "targeted therapies", particularly those drugs that inhibit the activity of tyrosine kinases, has become a remarkable progress in the treatment of neoplastic diseases. (
  • In addition, Brk deficient mice exhibited increased Akt kinase activity. (
  • Furthermore, IFN-γ-induced secretion was dependent on tyrosine protein kinase activity. (
  • ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. (
  • Results indicate that PI3-kinase activity was increased in response to silica. (
  • Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells. (
  • Discovery of N-(2-chloro-6-methylphneyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in pre-clinical assays. (
  • Tyrosine Protein Kinase CSK (C Src Kinase or Protein Tyrosine Kinase CYL or CSK or EC pipeline Target constitutes close to 12 molecules. (
  • 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. (
  • Smart drugs: tyrosine kinase inhibitors in cancer therapy. (
  • S B Bhise, Abhijit D. Nalawade and Hitesh Wadhawa, Role of protein tyrosine kinase inhibitors in cancer therapeutics . (
  • A catalog of 518 human protein kinases has been discerned from the human genome sequence ( 1 ). (
  • Approximately 2000 kinases are known and more than 90 Protein Tyrosine Kinases (PTKs) have been found in the human genome. (
  • This review summarizes recent advances in our understanding of endothelial receptor tyrosine kinase endocytosis and signaling using vascular endothelial growth factor receptor-2 as a paradigm. (
  • VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibitors have become first-line therapy for metastatic renal cell carcinoma. (
  • Is the Subject Area "In vitro kinase assay" applicable to this article? (
  • This application note describes the successful performance of Invitrogen´s PolarScreen™ Far-Red Kinase Assay on the Tecan Infinite™ F500 filter based multimode detection system. (
  • however, the role of tyrosine kinase-mediated phosphorylation is unclear. (
  • The Human Tyrosine Kinases RT 2 Profiler PCR Array profiles the expression of 84 receptor and non-receptor tyrosine kinase genes. (
  • The Human Kinases & Phosphatases qBiomarker Copy Number PCR Array profiles the copy number of 23 genes encoding kinases or phosphatases reported to undergo frequent genomic alterations. (
  • The first study to take advantage of both of these advances resequenced 138 genes, including all of the tyrosine kinase and tyrosine-kinase-like genes, in colon cancers, which resulted in the identification of 14 genes with somatic mutations, suggesting potential roles in carcinogenesis ( 4 ). (
  • Studies performing knockout of these genes have revealed that these kinase are associated with apoptosis (the cellular signaling leading to the deal of potentially cancerous cells) and immune response. (
  • Roles or expressions of Src family tyrosine kinases vary significantly according to cell type, as well as during cell growth and differentiation. (
  • Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. (
  • With the Human siGENOME Tyrosine Kinase siRNA Library, researchers can suppress the expression of receptor/non-receptor tyrosine kinases critical for the control of several cell processes, including cell cycle, shape, proliferation and differentiation. (
  • The dimerization of c-Src is mediated by the interaction of the myristoylated N-terminal region of one partner and the kinase domain of another partner. (
  • Exons 12-19 are predicted to encode the tyrosine kinase domain, within the intracellular region (Hubbard et al. (
  • The tyrosine kinase domain (aa 525-776) is within the intracellular region of the TYRO3 receptor. (