Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Protein Kinase C beta: 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.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Protein Kinase C-alpha: 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.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Protein Kinase C-delta: 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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Phorbol 12,13-Dibutyrate: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.DiglyceridesProtein Kinase C-epsilon: 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.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Phorbol Esters: Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine: A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Kinetics: The rate dynamics in chemical or physical systems.Benzophenanthridines: Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.MaleimidesIndoles: 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.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.PhenanthridinesAmino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.AMP-Activated Protein Kinases: 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.Cyclic AMP: 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.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.PhosphoproteinsBlotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Calcium-Calmodulin-Dependent Protein Kinase Type 2: 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.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Bryostatins: A group of 20-member macrolactones in which there are three remotely substituted pyran rings that are linked by a methylene bridge and an E-disubstituted alkene, and have geminal dimethyls at C8 and C18 carbons. Some interact with PROTEIN KINASE C.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.eIF-2 Kinase: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Casein Kinases: 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.Threonine: 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.Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.MAP Kinase Kinase 4: 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.Phosphoserine: The phosphoric acid ester of serine.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Enzyme Activators: Compounds or factors that act on a specific enzyme to increase its activity.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.3-Phosphoinositide-Dependent Protein Kinases: 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).Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Cattle: 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.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Ionomycin: A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.Adenosine Triphosphate: 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.PiperazinesCalcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Glycogen Synthase Kinase 3: 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.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Glycerides: GLYCEROL esterified with FATTY ACIDS.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Sphingosine: An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cyclic AMP-Dependent Protein Kinase Type II: A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.Cell Line, Tumor: A cell line derived from cultured tumor cells.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.ChromonesAcetophenonesEpidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Pyruvate Kinase: 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 2.7.1.40.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Molecular Weight: The sum of the weight of all the atoms in a molecule.Okadaic Acid: A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.MAP Kinase Kinase Kinase 1: 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.Myosin-Light-Chain Kinase: 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.I-kappa B Kinase: 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.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Morpholines8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Phosphothreonine: The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.Mitogen-Activated Protein Kinase 8: 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.Ribosomal Protein S6 Kinases, 90-kDa: 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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Phospholipase D: An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.MAP Kinase Kinase 2: A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.A Kinase Anchor Proteins: A structurally-diverse family of intracellular-signaling adaptor proteins that selectively tether specific protein kinase A subtypes to distinct subcellular sites. They play a role in focusing the PROTEIN KINASE A activity toward relevant substrates. Over fifty members of this family exist, most of which bind specifically to regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASE TYPE II such as CAMP PROTEIN KINASE RIIALPHA or CAMP PROTEIN KINASE RIIBETA.Insulin: 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).Benzopyrans: Compounds with a core of fused benzo-pyran rings.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Focal Adhesion Kinase 1: A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.Cell Cycle Proteins: 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.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Proto-Oncogene Proteins c-raf: A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.PhosphopeptidesUp-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.CDC2-CDC28 Kinases: 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.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Inositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Butadienes: Four carbon unsaturated hydrocarbons containing two double bonds.Thymidine Kinase: 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 2.7.1.21.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesCyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Focal Adhesion Protein-Tyrosine Kinases: A family of non-receptor, PROLINE-rich protein-tyrosine kinases.Cell Cycle: 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.Genistein: An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.Protein Phosphatase 1: A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.Aurora Kinases: 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.Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.PC12 Cells: 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.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Sulfonamides: A group of compounds that contain the structure SO2NH2.

Intracellular signalling: PDK1--a kinase at the hub of things. (1/15539)

Phosphoinositide-dependent kinase 1 (PDK1) is at the hub of many signalling pathways, activating PKB and PKC isoenzymes, as well as p70 S6 kinase and perhaps PKA. PDK1 action is determined by colocalization with substrate and by target site availability, features that may enable it to operate in both resting and stimulated cells.  (+info)

PKCdelta acts as a growth and tumor suppressor in rat colonic epithelial cells. (2/15539)

We have analysed the expression of three calcium-independent isoforms of protein kinase C (PKC), PKCdelta, PKCepsilon and PKCzeta, in an in vitro model of colon carcinogenesis consisting of the nontumorigenic rat colonic epithelial cell line D/WT, and a derivative src-transformed line D/src. While PKCzeta and PKCepsilon showed similar protein levels, PKCdelta was markedly decreased in D/src cells when compared to the D/WT line. To assess whether down-regulation of PKCdelta was causally involved in the neoplastic phenotype in D/src cells, we prepared a kinase-defective mutant of PKCdelta. Stable transfection of this sequence caused morphological and growth changes characteristic of partial transformation in D/WT cells. Moreover, to test whether PKCdelta was involved in growth control and transformation in this model, we overexpressed PKCdelta in D/src cells. Transfected cells underwent marked growth and morphological modifications toward the D/WT phenotype. In a late stage in culture, transfected cells ceased to proliferate, rounded up and degenerated into multinucleated, giant-like cells. We conclude that PKCdelta can reverse the transformed phenotype and act as a suppressor of cell growth in D/src cells. Moreover, our data show that downregulation of this isoenzyme of PKC may cooperate in the neoplastic transformation induced by the src oncogene in D/WT cells.  (+info)

Activation of IkappaB kinase beta by protein kinase C isoforms. (3/15539)

The atypical protein kinase C (PKC) isotypes (lambda/iotaPKC and zetaPKC) have been shown to be critically involved in important cell functions such as proliferation and survival. Previous studies have demonstrated that the atypical PKCs are stimulated by tumor necrosis factor alpha (TNF-alpha) and are required for the activation of NF-kappaB by this cytokine through a mechanism that most probably involves the phosphorylation of IkappaB. The inability of these PKC isotypes to directly phosphorylate IkappaB led to the hypothesis that zetaPKC may use a putative IkappaB kinase to functionally inactivate IkappaB. Recently several groups have molecularly characterized and cloned two IkappaB kinases (IKKalpha and IKKbeta) which phosphorylate the residues in the IkappaB molecule that serve to target it for ubiquitination and degradation. In this study we have addressed the possibility that different PKCs may control NF-kappaB through the activation of the IKKs. We report here that alphaPKC as well as the atypical PKCs bind to the IKKs in vitro and in vivo. In addition, overexpression of zetaPKC positively modulates IKKbeta activity but not that of IKKalpha, whereas the transfection of a zetaPKC dominant negative mutant severely impairs the activation of IKKbeta but not IKKalpha in TNF-alpha-stimulated cells. We also show that cell stimulation with phorbol 12-myristate 13-acetate activates IKKbeta, which is entirely dependent on the activity of alphaPKC but not that of the atypical isoforms. In contrast, the inhibition of alphaPKC does not affect the activation of IKKbeta by TNF-alpha. Interestingly, recombinant active zetaPKC and alphaPKC are able to stimulate in vitro the activity of IKKbeta but not that of IKKalpha. In addition, evidence is presented here that recombinant zetaPKC directly phosphorylates IKKbeta in vitro, involving Ser177 and Ser181. Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation.  (+info)

Promoter and exon-intron structure of the protein kinase C gene from the marine sponge Geodia cydonium: evolutionary considerations and promoter activity. (4/15539)

We report the gene structure of a key signaling molecule from a marine sponge, Geodia cydonium. The selected gene, which codes for a classical protein kinase C (cPKC), comprises 13 exons and 12 introns; the introns are, in contrast to those found in cPKC from higher Metazoa, small in size ranging from 93 nt to 359 nt. The complete gene has a length of 4229 nt and contains exons which encode the characteristic putative regulatory and catalytic domains of metazoan cPKCs. While in the regulatory domain only one intron is in phase 0, in the catalytic domain most introns are phase 0 introns, suggesting that the latter only rarely undergo module duplication. The 5'-flanking sequence of the sponge cPKC gene contains a TATA-box like motif which is located 35-26 nt upstream from the start of the longest sequenced cDNA. This 5'-flanking sequence was analyzed for promoter activity. The longest fragment (538 nt) was able to drive the expression of luciferase in transient transfections of NIH 3T3 fibroblasts; the strong activity of the sponge promoter was found to be half the one displayed by the SV40 reference promoter. Deletion analysis demonstrates that the AP4 site and the GC box which is most adjacent to the TATA box are the crucial elements for maximal promoter activity. The activity of the promoter is not changed in 3T3 cells which are kept serum starved or in the presence of a phorbol ester. In conclusion, these data present the phylogenetically oldest cPKC gene which contains in the 5'-flanking region a promoter functional in the heterologous mammalian cell system.  (+info)

Phosphorylation by protein kinase C decreases catalytic activity of avian phospholipase C-beta. (5/15539)

The potential role of protein kinase C (PKC)-promoted phosphorylation has been examined in the G-protein-regulated inositol lipid signalling pathway. Incubation of [32P]Pi-labelled turkey erythrocytes with either the P2Y1 receptor agonist 2-methylthioadenosine triphosphate (2MeSATP) or with PMA resulted in a marked increase in incorporation of 32P into the G-protein-activated phospholipase C PLC-betaT. Purified PLC-betaT also was phosphorylated by PKC in vitro to a stoichiometry (mean+/-S. E.M.) of 1.06+/-0.2 mol of phosphate/mol of PLC-betaT. Phosphorylation by PKC was isoenzyme-specific because, under identical conditions, mammalian PLC-beta2 also was phosphorylated to a stoichiometry near unity, whereas mammalian PLC-beta1 was not phosphorylated by PKC. The effects of PKC-promoted phosphorylation on enzyme activity were assessed by reconstituting purified PLC-betaT with turkey erythrocyte membranes devoid of endogenous PLC activity. Phosphorylation resulted in a decrease in basal activity, AlF4(-)-stimulated activity, and activity stimulated by 2MeSATP plus guanosine 5'-[gamma-thio]triphosphate in the reconstituted membranes. The decreases in enzyme activities were proportional to the extent of PKC-promoted phosphorylation. Catalytic activity assessed by using mixed detergent/phospholipid micelles also was decreased by up to 60% by phosphorylation. The effect of phosphorylation on Gqalpha-stimulated PLC-betaT in reconstitution experiments with purified proteins was not greater than that observed on basal activity alone. Taken together, these results illustrate that PKC phosphorylates PLC-betaT in vivo and to a physiologically relevant stoichiometry in vitro. Phosphorylation is accompanied by a concomitant loss of enzyme activity, reflected as a decrease in overall catalytic activity rather than as a specific modification of G-protein-regulated activity.  (+info)

Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli. (6/15539)

Inflammatory mediators such as histamine and thrombin increase the tight-junction permeability of endothelial cells. Tight-junction permeability may be independently controlled, but is dependent on the adherens junction, where adhesion is achieved through homotypic interaction of cadherins, which in turn are associated with cytoplasmic proteins, the catenins. p120, also termed p120(cas)/p120(ctn), and its splice variant, p100, are catenins. p120, originally discovered as a substrate of the tyrosine kinase Src, is also a target for a protein kinase C-stimulated pathway in epithelial cells, causing its serine/threonine dephosphorylation. The present study shows that pharmacological activation of protein kinase C stimulated a similar pathway in endothelial cells. Activation of receptors for agents such as histamine (H1), thrombin and lysophosphatidic acid in the endothelial cells also caused serine/threonine dephosphorylation of p120 and p100, suggesting physiological relevance. However, protein kinase C inhibitors, although blocking the effect of pharmacological activation of protein kinase C, did not block the effects due to receptor activation. Calcium mobilization and the myosin-light-chain-kinase pathway do not participate in p120/p100 signalling. In conclusion, endothelial cells possess protein kinase C-dependent and -independent pathways regulating p120/p100 serine/threonine phosphorylation. These data describe a new connection between inflammatory agents, receptor-stimulated signalling and pathways potentially influencing intercellular adhesion in endothelial cells.  (+info)

Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (7/15539)

Activation of the extracellularly regulated kinase (ERK) pathway is part of the early biochemical events that follow lipopolysaccharide (LPS) treatment of macrophages or their infection by virulent and attenuated Salmonella strains. Phagocytosis as well as the secretion of invasion-associated proteins is dispensable for ERK activation by the pathogen. Furthermore, the pathways used by Salmonella and LPS to stimulate ERK are identical, suggesting that kinase activation might be solely mediated by LPS. Both stimuli activate ERK by a mechanism involving herbimycin-dependent tyrosine kinase(s) and phosphatidylinositol 3-kinase. Phospholipase D activation and stimulation of protein kinase C appear to be intermediates in this novel pathway of MEK/ERK activation.  (+info)

Role of iron in Nramp1-mediated inhibition of mycobacterial growth. (8/15539)

Innate resistance to mycobacterial growth is mediated by a gene, Nramp1. We have previously reported that Nramp1 mRNA from macrophages of Mycobacterium bovis BCG-resistant (Bcgr) mice is more stable than Nramp1 mRNA from macrophages of BCG-susceptible (Bcgs) mice. Based on these observations and on reports that show that the closely related Nramp2 gene is a metal ion transporter, we evaluated the effect of iron on the growth of Mycobacterium avium within macrophages as well as on the stability of Nramp1 mRNA. The addition of iron to macrophages from Bcgs mice resulted in a stimulation of mycobacterial growth. In contrast, iron increased the capacity of macrophages from Bcgr mice to control the growth of M. avium. When we treated recombinant gamma interferon (IFN-gamma)-activated macrophages with iron, we found that iron abrogated the growth inhibitory effect of IFN-gamma-activated macrophages from Bcgs mice but that it did not affect the capacity of macrophages from Bcgr mice to control microbial growth. A more detailed examination of the effect of iron on microbial growth showed that the addition of small quantities of iron to resident macrophages from Bcgr mice stimulated antimicrobial activity within a very narrow dose range. The effect of iron on the growth inhibitory activity of macrophages from Bcgr mice was abrogated by the addition of catalase or mannitol to the culture medium. These results are consistent with an Fe(II)-mediated stimulation of the Fenton/Haber-Weiss reaction and hydroxyl radical-mediated inhibition of mycobacterial growth.  (+info)

K04166 AGTR1; angiotensin II receptor type 1 K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha K04635 GNA11; guanine nucleotide-binding protein subunit alpha-11 K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11] K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1 K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2 K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3 K02677 PRKCA; classical protein kinase C alpha type [EC:2.7.11.13] K19662 PRKCB; classical protein kinase C beta type [EC:2.7.11.13] K19663 PRKCG; classical protein kinase C gamma type [EC:2.7.11.13] K18050 PRKCE; novel protein kinase C epsilon type [EC:2.7.11.13] K06070 PKD; protein kinase D [EC:2.7.11.13] K06070 PKD; protein kinase D [EC:2.7.11.13] K06070 PKD; protein ...
Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Kmfor C3 was 2.6 µM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that ...
TY - JOUR. T1 - Identification of a nuclear protein binding element within the rat brain protein kinase C γ promoter that is related to the developmental control of this gene. AU - Chen, Kuang Hua. AU - Widen, Steven. AU - Wilson, Samuel H.. AU - Huang, Kuo Ping. PY - 1993/7/5. Y1 - 1993/7/5. N2 - Protein kinase C γ (PKC γ) is a brain-specific isozyme expressed at a high level in the adult but not in the fetal or newborn rat. At least seventeen nuclear protein binding sites within the 5-flanking region extending from -1612 to +243 had been identified by DNase I footprinting analysis and gel mobility shift assays. Among them, one site, GAATTAATAGG, at -669 to -679 is protected from DNase I digestion by nuclear protein from newborn but not from the adult rat brain. The levels of this binding protein, as determined by gel mobility shift assay, were found inversely related to the levels of PKC γ in rat brain at different stages of development. These results suggest that this particular binding ...
TY - JOUR. T1 - A role for protein kinase C-mediated phosphorylation in eliciting glucagon desensitization in rat hepatocytes. AU - Savage, A.. AU - Zeng, L.. AU - Houslay, M. D.. PY - 1995/4/1. Y1 - 1995/4/1. N2 - An immobilized hepatocyte preparation was used to show that both vasopressin and glucagon could desensitize the ability of glucagon to increase intracellular cyclic AMP concentrations. This process was not dependent on any influx of extracellular Ca2+ and was not mediated by any rise in the intracellular level of Ca2+. The protein kinase C-selective inhibitors chelerythrine, staurosporine and calphostin C acted as potent inhibitors of the desensitization process but with various degrees of selectivity regarding their ability to inhibit the desensitizing actions of glucagon and vasopressin. The protein phosphatase inhibitor okadaic acid was just as potent as vasopressin and glucagon in causing desensitization. Treatment of hepatocyte membranes with alkaline phosphatase restored to near ...
We previously established a cell line from a patient with acute myelomonocytic leukemia with eosinophilia (M4E0), ME-1. ME-1 cells are responsive to colony-stimulating factors (CSFs) such as interleukin-3 (IL-3), IL-4, and granulocyte-macrophage CSF (GM-CSF), and exhibit monocyte-macrophage differentiation. We isolated three subclones, ME-F1 from ME-1, and ME-F2 and ME-F3 from two sublines of ME-1. These subclones had different morphologic, cytochemical, phenotypic, and cytogenetic features. They represented different monocytic-lineage differentiation stages and exhibited different responses to IL-3, GM- CSF, and especially IL-4. IL-3, GM-CSF, and IL-4 enhanced proliferation and differentiation to macrophage-like cells in the ME-F1 subclone. However, they enhanced only proliferation of ME-F2 cells and only differentiation to macrophage-like cells in the ME-F3 subclone. To elucidate possible differences in signal transduction mechanisms in ME- F1, ME-F2, and ME-F3 cells following stimulation by ...
TY - JOUR. T1 - Modulation of chemosensitivity in human colon carcinoma cells by downregulating Protein Kinase Cα expression. AU - Chakrabarty, Subhas. AU - Huang, Shuang. PY - 1996/7/1. Y1 - 1996/7/1. N2 - Protein kinase C (PKC) is thought to play a role in tumor progression and drug resistance of colon carcinomas. Specifically, the PKCα isoform has been implicated in drug resistance and responsiveness of colon carcinoma cells to growth factors. Therefore, in this study we determined the effect of downregulating PKCα expression by transfecting human colon carcinoma cells with an antisense PKCα expression vector and then determined the sensitivity of these cells to the anticancer drugs mitomycin C (MMC), 5-fluorouracil (5-FU) and vincristine (Vin). Transiently transfecting the human colon carcinoma cell lines Moser, SW480 and HT29 with antisense PKCα expression vector (but not antisense PKCβ expression vector) consistently increased the sensitivity of these cells to MMC, 5-FU and VIN by ...
TY - JOUR. T1 - Differential effects of protein kinase C inhibitors on chemokine production in human synovial fibroblasts. AU - Jordan, Nicola J.. AU - Watson, Malcolm L.. AU - Yoshimura, Teizo. AU - Westwick, John. PY - 1996. Y1 - 1996. N2 - 1. Rheumatoid arthritis is associated with the accumulation and activation of selected populations of inflammatory cells within the arthritic joint. One putative signal for this process is the production, by resident cells, of a group of inflammatory mediators known as the chemokines. 2. The chemokines interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated on activation normal T-cell expressed and presumably secreted) are target-cell specific chemoattractants produced by synovial fibroblasts in response to stimulation with interleukin-1α (IL-1α) or tumour necrosis factor α (TNFα). The signalling pathways involved in their production are not well defined. We therefore used four different protein kinase C inhibitors to ...
TY - JOUR. T1 - Protein kinase C regulates the tonic but not the phasic component of contraction in guinea-pig ileum. AU - Sasaguri, T.. AU - Watson, S. P.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contraction to carbachol and high K+. In contrast, 4α-phorbol, which does not activate protein kinase C, had no effect on these responses. Exposure to phorbol 12-myristate 13-acetate (PMA; 1 μM) for up to 8 h induced a time-dependent loss of [3H]-PDBu binding sites, consistent with the down-regulation of protein kinase C by this treatment. The phasic component of contraction to carbachol or high K+ was unaffected following the down-regulation of protein kinase C. The tonic component of contraction to ...
Protein kinase C regulates the activity of a diverse group of cellular proteins including membrane ion channel proteins. Although protein kinase C and its substrate protein have been identified in both membrane and cytosolic fractions in the heart, the physiological role of this kinase in the regulation of cardiac function remains unknown. We examined the physiological role of protein kinase C by stimulating its activity with 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) in human trabeculae carneae. This resulted in decreased peak isometric twitch force and peak intracellular sarcoplasmic reticulum calcium release as detected with aequorin. Furthermore, in the presence of DPBA, steady-state force-[Ca2+] relations were shifted to higher intracellular calcium concentrations, and the Hill coefficient was reduced, indicating a decrease in responsiveness of the myofilaments to calcium and a change in cooperativity among thin filament proteins, respectively. Thus, DPBA affects not only ...
Effects of pentoxifylline and protein kinase C inhibitor on phorbol ester-induced intercellular adhesion molecule-1 expression in brain microvascular endothelial cells.
TY - JOUR. T1 - Inhibition of the spontaneous rate of contraction of neonatal cardiac myocytes by protein kinase C isozymes. T2 - A putative role for the ε isozyme. AU - Johnson, John A. AU - Mochly-Rosen, Daria. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Protein kinase C (PKC) enzymes regulate numerous cardiac functions. In the present study, we determined the effects of the PKC-activating drug 4-β phorbol 12-myristate 13-acetate (4-β PMA) on the rate of contraction and correlated these changes with the distribution and levels of α-, β-, δ-, ε-, and ζ-PKC isozymes by using neonatal rat cardiac myocytes in culture. Treatment with 0.3 to 100 nmol/L 4-β PMA caused negative chronotropic effects on contraction. This effect was maximal at a concentration of 3 nmol/L 4-β PMA and correlated with redistribution of the α- and ε-PKC isozymes from the cytosolic to the particulate cell fraction. After a 1-hour treatment with 100 nmol/L PMA, the α- and β-PKC isozymes and an 80-kD ζ- like PKC isozyme ...
TY - JOUR. T1 - Isolation and characterization of two new Drosophila protein kinase C genes, including one specifically expressed in photoreceptor cells. AU - Schaeffer, Eric. AU - Smith, Dean. AU - Mardon, Graeme. AU - Quinn, William. AU - Zuker, Charles. PY - 1989/5/5. Y1 - 1989/5/5. N2 - We have isolated and characterized two new protein kinase C (PKC) genes from D. melanogaster. One, dPKC98F, maps to chromosome region 98F and displays over 60% amino acid sequence identity with members of a recently described "PKC-related" subfamily in mammals. The other, dPKC53E(ey), maps to region 53E 4-7 on the second chromosome and lies within 50 kb of a PKC gene previously characterized (dPKC). While dPKC98F transcripts are expressed throughout development, expression of the two genes mapping at cytogenetic location 53E is primarily in adults. dPKC98F and the previously reported 53E gene are transcribed predominantly in brain tissue. In contrast, dPKC53E(ey) is transcribed only in photoreceptor cells. We ...
We found that removal of Ca2+ and inhibition of PKC prevented high Pi-induced O2·− production (Figures 3A and 3B), indicating a role for mechanosensitive Ca2+ signaling and PKC-dependent pathways in high Pi-induced upregulation of NAD(P)H oxidase activity. This idea is consistent with the findings that high Pi elicited significantly greater increases in smooth muscle [Ca2+]i than normal levels of Pi (Figure 4). The important role of Ca2+ signaling is also supported by the finding that administration of a Ca2+ ionophore resulted in significantly increased arterial O2·− production (Figure 3C). Further, pharmacological activation of PKC2 elicited substantial increases in arterial NAD(P)H oxidase-derived O2·− generation (Figure 3C). Because removal of Ca2+ during high-pressure treatment prevented endothelial dysfunction (Figure 1) and increases in O2·− production in high Pi-exposed arteries (Figure 3A) and phorbol ester-stimulated O2·− generation in normotensive arteries could also be ...
This investigation deals with the molecular mechanism of anti-human immunodeficiency virus type 1 (HIV-1) action of pentoxifylline (PTX) [1-(5′-oxohexyl)-3,7-dimethylxanthine] a drug widely used for the treatment of conditions involving defective regional microcirculation. The inhibition by PTX of protein kinase C (PKC) or cAMP-dependent protein kinase (PKA)-mediated activation by phorbol ester (PMA) and tumor necrosis factor alpha (TNF-α) of HIV-1-LTR-regulated reporter gene expression was studied in human CD4+ T lymphocytes (Jurkat) and human embryo kidney cells (293-27-2). A protein kinase C is involved in activation of NF-κB in whole cells, identified by using inhibitors specific for PKC- or PKA-catalyzed NF-κB activation in whole cell and cell-free systems. PTX inhibited PKC- or PKA-catalyzed activation of NF-κB in cytoplasmic extracts from unstimulated Jurkat or 293-27-2 cells, but not interaction of preactivated NF-κB with its motifs. Calphostin C, a specific inhibitor of PKC, inhibited NF
TY - JOUR. T1 - Photoactivated inhibition of superoxide generation and protein kinase C activity in neutrophils by blepharismin, a protozoan photodynamically active pigment. AU - Watanabe, Yoshiya. AU - E-ige, Keisuke. AU - Kobuchi, Hirotsugu. AU - Kato, Yoji. AU - Matsuoka, Tatsuomi. AU - Utsumi, Toshihiko. AU - Yoshioka, Tamotsu. AU - Horton, Alan A.. AU - Utsumi, Kozo. PY - 1995/2/14. Y1 - 1995/2/14. N2 - Blepharismin is an endogenous photosensitizing pigment found in the protozoan Blepharisma. This pigment inhibited the generation of Superoxide anion (O2-) in neutrophils not only via a diacylglycerol-induced protein kinase C (PKC)-dependent reaction but also by an arachidonate-induced PKC-independent reaction. The inhibition was light and concentration dependent for both reactions. Light-activated inhibition was strong at wavelengths between 520 and 570nm but not above 610nm. PKC activity in neutrophils and from rat brain was inhibited by blepharismin in a light- and concentration dependent ...
TY - JOUR. T1 - Differential effects of protein kinase C on the levels of epithelial Na+ channel subunit proteins. AU - Stockand, James D. AU - Hui-Fang, B.. AU - Schenck, J.. AU - Malik, B.. AU - Middleton, P.. AU - Schlanger, L. E.. AU - Eaton, D. C.. PY - 2000/8/18. Y1 - 2000/8/18. N2 - Regulation of epithelial Na+ channel (ENaC) subunit levels by protein kinase C (PKC) was investigated in A6 cells. PKC activation altered ENaC subunit levels, differentially decreasing the levels of both β and γ, but not αENaC. Temporal regulation of β and γENaC by PKC differed; γENaC decreased with a time constant of3.7 ± 1.0 h, whereas βENaC decreased in 13.9 ±3.0h. Activation of PKC also resulted in a decrease in trans-epithelial Na+ reabsorption for up to 48h. PMA activation of PKC resulted in negative feedback inhibition of PKC protein levels beginning within 4h. Both β and γENaC levels, as well as transport tended toward pretreatment values after 48 h of PMA treatment. PKC inhibitors ...
TY - JOUR. T1 - Synthesis and protein kinase C binding activity of benzolactam-V7. AU - Ma, Dawei. AU - Wang, Guoqiang. AU - Wang, Shaomeng. AU - Kozikowski, Alan P.. AU - Lewin, Nancy E.. AU - Blumberg, Peter M.. PY - 1999/5/17. Y1 - 1999/5/17. N2 - Benzolactam-V7 (3a), a simplified analogues of (-)-indolactam-V with twist-form conformation, was synthesized and evaluated as a new protein kinase C modulator. Both 3a and its-7-substituted analogue 3c showed weak binding activity to displace PDBU binding from recombinant PKCα.. AB - Benzolactam-V7 (3a), a simplified analogues of (-)-indolactam-V with twist-form conformation, was synthesized and evaluated as a new protein kinase C modulator. Both 3a and its-7-substituted analogue 3c showed weak binding activity to displace PDBU binding from recombinant PKCα.. UR - http://www.scopus.com/inward/record.url?scp=0033577690&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0033577690&partnerID=8YFLogxK. U2 - ...
TY - JOUR. T1 - Role of Ras in signal transduction from the nerve growth factor receptor. T2 - Relationship to protein kinase C, calcium and cyclic AMP. AU - Szeberenyi, J.. AU - Erhardt, P.. AU - Cai, H.. AU - Cooper, G. M.. PY - 1992/1/1. Y1 - 1992/1/1. N2 - A dominant inhibitory ras mutant (Ha-ras Asn-17) has been used to investigate the role of Ras in nerve growth factor (NGF)-mediated signal transduction in PC12 cells. Expression of Ha-Ras Asn-17 blocks neuronal differentiation of these cells in response to NGF treatment. The Ha-Ras Asn-17 block was bypassed by treatment with NGF plus dibutyryl cAMP or NGF plus the Ca2+ ionophore ionomycin, but not by NGF plus 12-O-tetradecanoyl phorbol acetate (TPA). Direct stimulation of the cAMP or Ca2+ pathways thus appeared to act synergistically with a Ras-independent NGF signaling pathway. This Ras-independent pathway was also distinct from protein kinase C, since its activity was not affected by protein kinase C down-regulation. It thus appears that ...
Protein Kinase C Theta Type (nPKC Theta or PRKCQ or EC 2.7.11.13) - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at Researchmoz.us
Correlation between endogenous membrane PKC activity and proliferation versus differentiation of normal and HPV16 transformed rat myoblast (L 6 cells): Histochem.J.
Catalytic domain of the Protein Serine/Threonine Kinase, Classical Protein Kinase C. Serine/Threonine Kinases (STKs), Classical (or Conventional) Protein Kinase C (cPKC) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC ...
The activity of calcium-, phospholipid-dependent protein kinase (PKc) was measured in (a) total extracts, (b) crude membrane, and (c) cytosolic fractions of chick embryo myogenic cells differentiating in culture. Total PKc activity slowly declines during the course of terminal myogenesis in contrast to the activity of cAMP-dependent protein kinase, which was also measured in the same cells. Myogenic cells at day 1 of culture possess high particulate and low soluble PKc activity. A dramatic decline of particulate PKc activity occurs during myogenic cell differentiation and is accompanied, through day 4, by a striking rise of the soluble activity. The difference in the subcellular distribution of PKc between replicating myoblasts and myotubes is confirmed by phosphorylation studies conducted in intact cells. These studies demonstrate that four polypeptides whose phosphorylation is stimulated by the tumor promoter 12-O-tetradecanoyl phorbol 13-acetate in myotubes, are spontaneously phosphorylated ...
Octadecadienoic acids (linoleic acid and linolelaidic acid) and the diacylglycerol, 1-oleoyl-2-acetyl-rac-glycerol (OAG) concentration-dependently induced activation of gel-filtered human platelets, i.e. aggregation and phosphorylation of 20 kDa and 47 kDa peptides. In contrast, octadecenoic acids (oleic and elaidic acid) and octadecanoic (stearic) acid were inactive. Octadecadienoic acid-induced platelet activation was suppressed by the protein kinase C inhibitor, polymyxin B, but not by the cyclooxygenase inhibitor, indomethacin. OAG-induced activation was potentiated by octadecadienoic acids present at non-stimulatory concentrations. Our data suggest that octadecadienoic acids and diacylglycerol synergistically induce platelet activation via protein kinase C. Furthermore, linolelaidic acid may provide a useful experimental tool to study fatty acid regulation of protein kinase C in intact cells. ...
TY - JOUR. T1 - "Functional mapping of the promoter region of the GNB2L1 human gene coding for RACK1 scaffold protein". AU - Del Vecchio, Igor. AU - Zuccotti, Annalisa. AU - Pisano, Federica. AU - Canneva, Fabio. AU - Lenzken, Silvia C.. AU - Rousset, Francoise. AU - Corsini, Emanuela. AU - Govoni, Stefano. AU - Racchi, Marco. PY - 2009/2/1. Y1 - 2009/2/1. N2 - RACK1 (Receptor for Activated C Kinase 1) is a scaffold protein for different kinases and membrane receptors. Previously, we characterized an age-dependent decline of RACK1 protein expression which could be counteracted with DHEA (dehydroepiandrosterone) [Corsini, E., et al. 2002. In vivo dehydroepiandrosterone restores age-associated defects in the protein kinase C signal transduction pathway and related functional responses. J. Immunol. 168, 1753-1758. and Corsini, E., et al. 2005. Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone. J. Leukoc. Biol. 77, 247-256.]. ...
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TY - JOUR. T1 - Chromatinized Protein Kinase C-theta: Can It Escape the Clutches of NF-kB?. AU - Sutcliffe, Elissa. AU - Li, Jasmine. AU - Zafar, Anjum. AU - Hardy, Kristine. AU - Ghildyal, Reena. AU - Norris, Nicole. AU - Lim, Chloe (Pek Siew). AU - Milburn, Peter. AU - Casarotto, Marco. AU - Denyer, Gareth. AU - Rao, Sudha. PY - 2012. Y1 - 2012. N2 - We recently provided the first description of a nuclear mechanism used by Protein Kinase C-theta (PKC-θ) to mediate T cell gene expression. In this mode, PKC-θ tethers to chromatin to form an active nuclear complex by interacting with proteins including RNA polymerase II, the histone kinase MSK-1, the demethylase LSD1, and the adaptor molecule 14-3-3ζ at regulatory regions of inducible immune response genes. Moreover, our genome-wide analysis identified many novel PKC-θ target genes and microRNAs implicated in T cell development, differentiation, apoptosis, and proliferation. We have expanded our ChIP-on-chip analysis and have now identified a ...
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We have provided clear evidence that insulin activation of all three signaling components, Viz., IRS-1-dependent PI 3-Kinase, atypical protein kinase C (aPKC) and PKB/Akt is defective in diabetic muscle. These defects are best seen when insulin activation is conducted at both half-maximal and maximal stimulation. Moreover, whereas previous studies had shown that treatment with metformin (Met) alone improves aPKC activation, or that treatment with thiazolidinedione (TZD) alone produces increases in activation of IRS-1/PI3K and aPKC when evaluated at maximal insulin stimulation, we have recently found that combined treatment with Met plus TZD for 6 weeks provokes marked increases in insulin effects on all three signaling factors at both half-maximal and maximal insulin stimulation. This work is being prepared for submission for publication.. We have also evaluated the improvement in insulin signaling in diabetic muscle 4 hours after acute endurance (one-legged) exercise and found that the ...
FIG. 3. Expression of PKC-α, -βI, and -βII isoforms in membrane and cytosolic fractions of DRG in experimental animals. Western blot analysis showed a single band of each isoform in all groups (A). Compared with nondiabetic littermate control mice (Lm) and transgenic mice (Tg), densitometric analysis disclosed reduced expression of membrane α isoform in both diabetic littermate mice (LmDM) and diabetic transgenic mice (TgDM), and the change in diabetic transgenic mice was more severe than in diabetic littermate mice (B). By contrast, cytosolic fraction of α isoform was contrariwise increased to a similar extent in both diabetic transgenic mice and diabetic littermate mice. Treatment with an ARI (fidarestat) corrected these changes in both diabetic groups (LmDM+ARI and TgDM+ARI). There was no change in βI expression in either membrane or cytosolic fraction among all groups. On the other hand, membrane βII expression tended to be elevated in diabetic littermate mice, and the increase was ...
|p|GF 109203X is a potent and selective inhibitor of protein kinase C [1].|/p||p| Protein kinase C (PKC) is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of serine and threon
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The acetylcholine analogue carbachol rapidly activated mitogen-activated protein kinase (MAPK), and caused tyrosine phosphorylation of the adapter protein p52 Shc and the epidermalgrowth factor (EGF) receptor, in human embryonic kidney cells stably expressing m3 muscarinic receptors. The protein kinase C (PKC) inhibitor GF109203X caused a significant partial inhibition of m3 receptor-mediated activation of MAPK. The PKC-independent MAPK activity elicited by carbachol in the presence of GF109203X was reproducibly abolished by AG1478, an inhibitor of EGF-receptor tyrosine kinase activity, and by the Src tyrosine kinase inhibitor PP1. In a subset of these experiments, GF109203X concomitantly increased carbachol-induced tyrosine phosphorylation of p52 Shc and the EGF receptor. In co-stimulation experiments, carbachol and EGF activated MAPK in a non-additive fashion; moreover, EGF-induced association of Shc with the phosphorylated EGF receptor was inhibited by carbachol. This effect of carbachol was ...
Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins, or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades. The PKC family consists of fifteen isozymes in humans. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, DAG, and a phospholipid such as phosphatidylserine for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ for activation. Thus, conventional and novel PKCs are ...
Treatment of intact NIH 3T3 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) causes a rapid redistribution (stabilization) of protein kinase C to the particulate fraction. Part of the enzyme activity stabilized to the membrane fraction in response to TPA can be recovered associated with nuclear-cytoskeletal components. An apparently pure nuclear fraction prepared from NIH 3T3 cells was found to contain 25-30% of the total membrane-associated protein kinase C activity when isolated in the presence of Ca2+. In untreated control cells, most of this activity found with the nuclear fraction can be extracted by chelators. Phorbol easter (TPA) treatment of NIH 3T3 cells induces the tight association of protein kinase C to the nucleus; this tightly bound activity is not dissociable by chelators and can be recovered only by solubilization with detergent. Nuclei purified from untreated human promyelocytic leukemic HL-60 cells contain higher amounts of chelator-stable, detergent-extractable protein ...
Mounting evidence points to a key role of PKC signaling in the pathology of AD, a degenerative disease characterized by loss of synapses and plasticity mechanisms in the brain. The disease is associated with the appearance of extracellular amyloid plaques caused by the mis-cleavage of amyloid precursor protein (APP) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein [83,84], two pathologies for which PKC involvement has been implicated over the years. But the critical importance of deregulated PKC signaling in AD was recently cemented by the results of an unbiased and comprehensive phosphoproteomic analysis of both human AD postmortem brains and brains from four AD mouse models [85]: PKC substrates accounted for over half of the core molecules that displayed increased phosphorylation in AD compared with control brains. The most robust increase in phosphorylation in AD compared with control brains occurred on MARCKS but also included PKC substrates such as ...
Chromatography of a maize seedling extract on DEAE-cellulose, followed by Octyl-Sepharose yielded a fraction with protein kinase activity which was stimulated by phosphatidylserine plus diolein. The activity was not enhanced by calcium ions but was inhibited by chelating agents and could then be restored by the addition of calcium ions. All these facts indicated that the maize protein kinase was similar to mammalian protein kinase C. The maize enzyme phosphorylated myelin basic protein (MBP) and histone H1, but the MBP-peptide4-14 and protamine were poor substrates for the enzyme. Further purification of the enzyme fraction followed by phosphorylation and SDS-polyacrylamide gel electrophoresis, revealed two labeled bands of Mw 59 and 83 kDa the former of which probably being the protein kinase C.. ...
Translocation of Ca2+/phospholipid-dependent protein kinase (PKC) activity from cytosolic to membrane fractions was assessed in washed human platelet suspensions. Phorbol myristate acetate (PMA) induced a rapid loss of PKC activity from the cytosolic compartment in stirred platelets, which was not accompanied by measurable increases in membrane-associated activity, but was paralleled by a decrease in total cellular enzyme activity (cytosol plus membrane). When platelet aggregation was prevented by not stirring, (i) cytosolic activity was decreased by PMA, (ii) significant and maintained (1-15 min with PMA) increases in membrane-bound PKC were detected, and (iii) the decline in total enzyme activity was markedly slower. In stirred platelets, total and specific inhibition of PMA-induced aggregation by a fibrinogen-derived peptide (RGDS, i.e. Arg-Gly-Asp-Ser) promoted maximal increases in membrane-associated PKC in the presence of PMA and completely prevented the loss in cellular activity. Thrombin ...
alpha-Tocopherol augmentation in human neutrophils was investigated for effects on neutrophil activation and tyrosine phosphorylation of proteins, through its modulation of protein kinase C (PKC) and tyrosine phosphatase activities. Incubation of neutrophils with alpha-tocopherol succinate (TS) resulted in a dose-dependent incorporation into cell membranes, up to 2.5 nmol/2 X 10(6) cells. A saturating dose of TS (40 mumol/l) inhibited oxidant production by neutrophils stimulated with phorbol myristate acetate (PMA) or opsonized zymosan (OZ) by 86 and 57%, as measured by luminol-amplified chemiluminescence (CL). With PMA, TS inhibited CL generation to a similar extent to staurosporine (10 nmol/l) or genistein (100 mumol/l), and much more than Trolox (40 mumol/l). With OZ, TS inhibited CL to a similar extent to Trolox. Neutrophil PKC activity was inhibited 50% or more by TS or staurosporine. the enzyme activity was unaffected by genistein or Trolox, indicating a specific interaction of ...
Recombinant Protein Kinase C, gamma (PRKCG) Protein. Species: Human. Source: Baculovirus infected Insect Cells. Order product ABIN411969.
This study identifies the regulation by PKC of a 40-pS-conductance KNDP subtype, but not a larger-conductance, 70-pS KATP channel of vascular smooth muscle cells. The properties of the 40- and 70-pS channels studied here are consistent with those previously described.11 12 13 14 Suppression of KNDP channel activity by PKC activation was due to an increased time spent in a long-lived interburst closed state, was mimicked by treatment with angiotensin II, and was completely blocked by pretreatment with the PKC inhibitor calphostin C or chelerythrine. The decline in KNDP channel activity due to PKC activation identified in this study may account for the previously reported reduction in whole-cell KATP currents after treatment of vascular myocytes with vasoconstrictors, phorbol esters, or diacylglycerol analogs,1 and therefore, for the contribution of this conductance to the regulation of vascular smooth muscle tone via intracellular signaling cascades involving PKC.. KATP currents have been ...
Among environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is one of the most potent tumor promoters and teratogens known. The molecular mechanisms responsible for the biological activity of TCDD, however, remain largely unknown. In this report, we show that the first observable effects of TCDD in cultured murine hepatoma cells are a rapid, transient increase in Ca2+ influx and a minor but significant elevation of activated, membrane-bound protein kinase C. These changes are then followed by induction of the immediate early proto-oncogenes c-fos, jun-B, c-jun, and jun-D, and by large increases in AP-1 transcription factor activity. Induction of these changes by TCDD is delayed compared with that by phorbol esters, although the magnitude of the effects caused by both treatments is similar, and both induction processes can be blocked by staurosporine, a protein kinase C inhibitor. In cultured cells, proto-oncogene induction by TCDD appears to be independent of the presence of a
Atypical protein kinase (PK)C isoforms, ζ and λ, have been reported to be activated by insulin via phosphoinositide 3-kinase, and have been suggested to be required for insulin-stimulated glucose transport. Here, we have examined the effects of transiently expressed wild-type (WT), constitutively active (Constit) and kinase-inactive (KI) forms of atypical PKCs, ζ and λ, on haemagglutinin antigen (HAA)-tagged glucose transporter 4 (GLUT4) translocation in rat adipocytes, and compared these effects with each other and with those of comparable forms of conventional (α, β) and novel (δ, ε) PKCs, which have also been proposed to be required for insulin-stimulated glucose transport. KI-PKC-ζ evoked consistent, sizeable (overall mean of 65%) inhibitory effects on insulin-stimulated, but not basal or guanosine-5´-[γ-thio]triphosphate-stimulated, HAA-GLUT4 translocation; moreover, inhibitory effects of KI-PKC-ζ were largely reversed by co-transfection of WT-PKC-ζ. Like KI-PKC-ζ, KI-PKC-λ ...
Studies have also advised the reduction of PKC theta expression may be responsible for inhibition of kit expression in GISTs, hence isnt going to react to KIT staining. Protein kinase C theta kinase inhibitor library for screening is really a novel protein kinase, downstream eector while in the kit signaling process that is associated with T cell activation, signal trans duction, and neuronal dierentiation. Various scientific studies have shown that PKC theta is strongly expressed and is overexpressed in GISTs, but not in other sarcomas. These scientific studies established PKC theta being a diagnostic marker for GIST. In study conducted by kim et al. on 220 GIST tumors, 212 had been positive to PKC theta while KIT was constructive in 216. However, two samples which can be PKC theta good and KIT adverse showed mutation in PDGFRA, indicating that PKC theta may possibly be a practical marker in diagnosing KIT damaging PDGFRA mutation tumors.. Whilst, other investigators feel that PKC theta ...
We have identified the gene encoding the only atypical PKC isoform in Drosophila and show that DaPKC binds directly to Baz and is colocalized with Baz in epithelia and neuroblasts. Apical localization of DaPKC is lost in baz mutants and vice versa, demonstrating that both proteins are mutually dependent on each other for correct localization. In neuroblasts, localization of DaPKC is not only dependent on Baz, but also on Insc. Baz levels are strongly reduced in neuroblasts of insc mutant embryos, most likely because Insc is required for stabilization of Baz (Schober et al. 1999; Wodarz et al. 1999; Yu et al. 2000). Thus, the effect of Insc on DaPKC localization is probably indirect and can be explained by the loss of Baz in insc mutant neuroblasts. Another protein, partner of Insc (Pins), has recently been identified as a binding partner of Insc (Schaefer et al. 2000; Yu et al. 2000). Pins, Baz, and Insc are mutually dependent on each other for correct localization and/or stability (Schaefer et ...
Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase C iota (PKCι) is a member of the atypical protein kinase C family and an important downstream mediator in the phosphoinositide pathway. PKCι expression was found to be upregulated in a subset of breast cancers and breast cancer cell lines. Introduction of mutant, oncogenic PIK3CA, but not wild-type PIK3CA, into breast mammary epithelial cells increased both the expression and activation of PKCι. In breast cancer cell lines overexpressing PKCι, depletion of PKCι increased the number of senescent cells, as assessed by senescence-associated β-galactosidase, morphology and bromodeoxyuridine incorporation. This phenomenon was not restricted to breast cancer cells, as it was also seen in glioblastoma cells. Senescence induction ...
The members of the protein kinase C (PKC) family consist of serine/threonine kinases classified according to their regulatory domain. Those that belong to the novel PKC subfamily, such as PKCδ, are dependent on diacylglycerol but not Calcium when considering their catalytic activity. Although several studies have shown the importance of PKCδ in different cellular events in health and disease, the overall in vivo distribution of this PKC isoform during development is still lacking. Through Lac Z and antibody staining procedures, we show here the in vivo expression of PKCδ during mouse embryogenesis. Ganglia were the domains with most prominent expression of PKCδ in most of the stages analysed, although PKCδ could also be detected in heart and somites at earlier stages, and cartilage primordium and skin among other sites in older embryos. The strong expression of PKCδ in ganglia during murine development shown in this study suggests a significant role of this isoform as well as redundancy with other
Buy Toddalin chloride (CAS 3895-92-9), a cell-permeable, water soluble selective protein kinase C inhibitor; Apoptosis inducer. Join researchers using high…
UCN-01 (7-hydroxy-staurosporine) is a potent and selective inhibitor of protein kinase C (PKC), one of several protein kinases examined. UCN-01 itself was shown to exhibit antitumor activity in vitro and in vivo in oncogene-activated human and murine tumor cell lines. Since the mechanism(s) of actio …
I have started measuring in-situ Protein Kinase C activity in permeabilized cells grown in 96-well plates, based on a few references from the literature such as: Heasley L.E., J.Biol.Chem., 1989, 264, 8646. I always get high activity after stimulation with phorbol esters and very low activity after treatment with PKC inhibitors. The problem is that the activity in untreated cells is often almost as high as in stimulated cells. Any advice or protocol would be welcome. Thanks Bernard medbpl at emory.edu ...
Protein kinase C activation[edit]. PIP2 cleavage to IP3 and DAG initiates intracellular calcium release and PKC activation. ... "Protein Kinase C as the Receptor for the Phorbol Ester Tumor Promoters: Sixth Rhoads Memorial Award Lecture". Cancer Research. ... whereas DAG is a physiological activator of protein kinase C (PKC). The production of DAG in the membrane facilitates ... Diacylglycerol can be phosphorylated to phosphatidic acid by diacylglycerol kinase. Insulin resistance[edit]. Activation of PKC ...
The active site is a region on an enzyme which a particular protein or substrate can bind to. The active site will only allow ... "Functional Design of Proteins". Molecular Cell Biology. 4th edition. W. H. Freeman. ...
COX-2 up-regulation has also been linked to the phosphorylation and activation of the E3 ubiquitin ligase HDM2, a protein that ...
1.7% in typical proteins) and is sensitive to oxidation. RI is also rich in leucine (21.5%, compared to 9% in typical proteins ... The affinity of RI for ribonucleases is among the highest for any protein-protein interaction; the dissociation constant of the ... It is a major cellular protein, comprising ~0.1% of all cellular protein by weight, and appears to play an important role in ... Ribonuclease inhibitor (RI) is a large (~450 residues, ~49 kDa), acidic (pI ~4.7), leucine-rich repeat protein that forms ...
Protein kinase *Tyrosine-kinase *Janus kinase. Hydrolase (EC 3). *3.1 Phosphodiesterase. *Acetylcholinesterase ...
Click on genes, proteins and metabolites below to link to respective articles. [§ 1] ... Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate ... Decreasing of specific protein prenylation[edit]. Statins, by inhibiting the HMG CoA reductase pathway, simultaneously inhibit ... The sterol response elements then facilitate increased transcription of various other proteins, most notably, LDL receptor. The ...
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 kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... As a consequence, if two protein kinase inhibitors both bind in the active site with similar affinity, but only one has to ... 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". ...
It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion ... 2001). The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. JBC papers in press. ... A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of ... Trypsinogen is an inactive form of trypsin, its inactive form ensures protein aspects of the body, such as the pancreas and ...
... and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles. ...
kinase activity. • protein binding. • ATP binding. • protein serine/threonine kinase activity. • protein kinase activity. ... Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... "Complex formation and cooperation of protein kinase C theta and Akt1/protein kinase B alpha in the NF-kappa B transactivation ...
protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • protein ... Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is ... "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... protein serine/threonine kinase activity. • identical protein binding. • MAP kinase kinase activity. ...
protein tyrosine kinase activity. • nucleotide binding. • MAP kinase kinase activity. • protein kinase activity. • protein ... protein serine/threonine kinase activator activity. • protein binding. • protein serine/threonine/tyrosine kinase activity. • ... This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... membrane protein proteolysis. • phosphorylation. • transmembrane receptor protein tyrosine kinase signaling pathway. • positive ... transmembrane receptor protein tyrosine kinase activity. • receptor tyrosine kinase. • transmembrane signaling receptor ... "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): ...
protein kinase activity. • kinase activity. • protein binding. • transmembrane receptor protein tyrosine kinase activity. • ... protein tyrosine kinase collagen receptor activity. • protein tyrosine kinase activity. • ATP binding. • collagen binding. ... transmembrane receptor protein tyrosine kinase signaling pathway. • regulation of bone mineralization. • positive regulation of ... protein phosphorylation. • cell adhesion. • positive regulation of osteoblast differentiation. • chondrocyte proliferation. • ...
This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity ... October 2004). "A rapid method for determining protein kinase phosphorylation specificity". Nat. Methods. 1 (1): 27-9. doi: ... Use of Oriented Peptide Libraries to determine phosphopeptide binding specificity and protein kinase substrate specificity[edit ... 2.2 Use of Oriented Peptide Libraries to determine phosphopeptide binding specificity and protein kinase substrate specificity ...
Protein kinase * بازدارنده تیروزین-کیناز * Janus kinase. هیدرولاز (EC 3). * 3.1 Phosphodiesterase ...
"Interaction of focal adhesion kinase with cytoskeletal protein talin". The Journal of Biological Chemistry. 270 (28): 16995-9. ... protein binding. • vinculin binding. • protein complex binding. • actin binding. • cadherin binding. • phosphatidylserine ... "Protein sequence of human TLN1 (Uniprot ID: Q9Y490)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 7 July ... Talin-1 is a protein that in humans is encoded by the TLN1 gene.[5][6] Talin-1 is ubiquitously expressed, and is localized to ...
... including protein kinase C,[40][41] however, the proteins considered the most likely molecular targets of anaesthetics are ion ... affects the function of membrane proteins by binding to the specific site on the protein. Thus, some membrane proteins are ... Slater SJ, Cox KJ, Lombardi JV, Ho C, Kelly MB, Rubin E, Stubbs CD (July 1993). "Inhibition of protein kinase C by alcohols and ... Hemmings HC Jr; Adamo AI (1994). "Effects of halothane and propofol on purified brain protein kinase C activation". ...
Others examine the composition of protein kinase inhibitors.[24] The most recent patents are specific the methodologies of ... "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] ...
Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression". European Journal of Biochemistry / ... "Regulation of cell motility by mitogen-activated protein kinase". The Journal of Cell Biology. 137 (2): 481-92. doi:10.1083/jcb ... G-protein coupled receptor activity. • signal transducer activity. • cannabinoid receptor activity. Cellular component. • ... The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that ...
"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National ... protein dimerization activity. • transcription factor activity, sequence-specific DNA binding. • protein complex binding. • ... Iijima S, Teraoka H, Date T, Tsukada K (June 1992). "DNA-activated protein kinase in Raji Burkitt's lymphoma cells. ... protein complex. • nucleolus. • nucleus. • nuclear chromatin. Biological process. • Notch signaling pathway. • chromatin ...
FASTKD5: encoding protein FAST kinase domain-containing protein 5 (FASTKD5). *FITM2: encoding protein Fat storage-inducing ... PANK2: pantothenate kinase 2 (pantothenate kinase-associated neurodegeneration). *PKIG: encoding protein cAMP-dependent protein ... encoding protein Transmembrane prostate androgen-induced protein. *TTPAL: encoding protein Tocopherol (alpha) transfer protein- ... YTHDF1: encoding protein YTH domain family, member 1. *ZFP64 encoding protein Zinc finger protein 64 homolog, isoforms 1 and 2 ...
Protein kinase activationEdit. cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein ... Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane- ... Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory ... Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP ...
1985). "Amino terminal myristylation of the protein kinase p60src, a retroviral transforming protein". Science. 227 (4685): 427 ... 1990). "Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly". AIDS Res. Hum. Retroviruses. 6 (6 ... Tashiro A, Shoji S, Kubota Y (1990). "Antimyristoylation of the gag proteins in the human immunodeficiency virus-infected cells ... Zhou W, Resh MD (1997). "Differential membrane binding of the human immunodeficiency virus type 1 matrix protein". J. Virol. 70 ...
Protein kinase C beta II (PKCβII) has been implicated in diabetic nephropathy (DN). Mesangial cell (MC) hypertrophy is a ... Protein kinase C beta II (PKCβII) has been implicated in diabetic nephropathy (DN). Mesangial cell (MC) hypertrophy is a ... Ser-660 phosphorylation of protein kinase C beta II ( PKCβII) by mammalian target of rapamycin complex 2 (mTORC2) regulates ... HG significantly increased phosphorylation of PKCβII at Ser-660 in a PI 3 kinase-dependent manner. siRNAs against PKCβII, ...
C-reactive protein (CRP) is a member of a large group of plasma proteins called acute phase proteins (APPs) which show elevated ... An evaluation of changes over time in serum creatine kinase activity and C-reactive protein concentration in dogs undergoing ... The serum activity of creatine kinase and serum concentration of C-reactive protein were evaluated preoperatively and then at 4 ... Thereafter there were significant differences in creatine kinase activity levels between the 2 groups. C-reactive protein ...
... with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this ... with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this ... with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this ... with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this ...
MAP kinase kinase kinase (MAP3K or MKKK). *MAP kinase kinase kinases *MAP3K1 ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... is performed by members of the Ste7 protein kinase family, also known as MAP2 kinases. MAP2 kinases in turn, are also activated ...
... protein kinases are implicated in a broad variety of diseases, including cancers and neurodegenerative conditions, and offer ... Assays for Mitogen-Activated Protein Kinase (MARK) Subtypes and MARK Activating Protein Kinase-2 (MAPKAP K-2) Using a Common ... Analysis of Protein Kinase Subcellular Localization by Visualization of GFP Fusion Proteins ... In Protein Kinase Protocols, a panel of highly skilled laboratory investigators describe both basic and more sophisticated ...
Protein kinase C (PKC). is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ... A serine/threonine protein kinase (EC 2.7.11.1) is a kinase enzyme that phosphorylates the OH group of serine or threonine ( ... Protein Kinase B, also known as AKT kinase. The v-akt gene was identified as the oncogene of retrovirus AKT8. The gene codes ...
Norway rat protein-coding gene Mapk1. Represented by 134 ESTs from 65 cDNA libraries. Corresponds to reference sequence NM_ ... Protein sequence * * Protein/EST matches (ProtEST) * * Protein/protein matches (BLink) * mitogen-activated protein kinase 1. C ... Protein sequence * * Protein/EST matches (ProtEST) * * Protein/protein matches (BLink) * mitogen-activated protein kinase 1. X ... Protein sequence * * Protein/EST matches (ProtEST) * * Protein/protein matches (BLink) * mitogen-activated protein kinase 8. C ...
Lambda/iota protein kinase C-interacting protein; Lambda-interacting protein; LIP; Phosphatidylinositol 3-kinase-related kinase ... Phosphatidylinositol 3-kinase-related kinase; Phosphatidylinositol 3-kinase-related protein kinase; PI-3-kinase-related kinase ... 61E3.4; ATX; hSMG-1; KIAA0421; Lambda/iota protein kinase C-interacting protein; Lambda-interacting protein; LIP; ... Heat shock protein 90 regulates phosphatidylinositol 3-kinase-related protein kinase family proteins together with the RUVBL1/2 ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Protein kinase C zeta plays a central role in activation of the p42/44 mitogen-activated protein kinase by endotoxin in ... This group represents protein kinase C (KPC), including zeta/iota types from mammals, protein kinase C-like 3 from round worms ...
Mitogen-activated protein kinase pathways.. Robinson MJ1, Cobb MH.. Author information. 1. University of Texas Southwestern ... Nearly all cell surface receptors utilize one or more of the mitogen-activated protein kinase cascades in their repertoire of ... MAP Kinase Kinase Kinase 1*. *Mammals. *Mitogen-Activated Protein Kinase Kinases*. *Protein-Serine-Threonine Kinases/metabolism ...
... and methods of using them to treat tyrosine kinase-dependent diseases and conditions in mammals: wherein n is an integer, ... regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, ... Protein tyrosine kinase inhibitors. US20090298855 *. Jul 28, 2009. Dec 3, 2009. Critical Outcome Technologies Inc.. Protein ... The FLK family is comprised of the kinase insert domain receptor (KDR), fetal liver kinase-1 (FLK-1), fetal liver kinase-4 (FLK ...
AMP-activated protein kinase (AMPK), an energy sensor, can regulate protein and lipid metabolism responding to alterations in ...
... including the tumor suppressor protein p53, the SV40 large T antigen and several transcription factors. ... DNA-Dependent Protein Kinase (DNA-PK) phosphorylates several DNA-binding substrates in vitro, ... cAMP-Dependent Protein Kinase, Catalytic Subunit. Purified kinase for protein phosphorylation and signal transduction studies. ... Kinase-Glo® Luminescent Kinase Assays. Determines activity of purified kinases by quantifying ATP remaining after a kinase ...
MGI protein superfamily detail pages represent the protein classification set for a homeomorphic superfamily from the Protein ... Term: pyruvate kinase. ID: PIRSF000678 Mouse Protein Superfamily Annotations. Select one or more mouse PIRSF members to ... The number of protein sequences returned does not always match the numbers of homologs shown, because the same protein sequence ... You can also "Select all" mouse superfamily members to obtain their protein sequences and the protein sequences for all mouse, ...
Our data indicate that protein kinase C (PKC) is required for the proper assembly of tight junctions. Low concentrations of the ... We have now examined in detail the role of protein kinases in intercellular junction biogenesis by using a combination of ... Regulated assembly of tight junctions by protein kinase C. R O Stuart and S K Nigam ... Identity of the 330- and 65-kDa phosphoproteins remains to be determined, but the 65-kDa protein may be occludin. The mass of ...
View protein in PROSITE. PS00107 PROTEIN_KINASE_ATP, 1 hit. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 ... View protein in PROSITE. PS00107 PROTEIN_KINASE_ATP, 1 hit. PS50011 PROTEIN_KINASE_DOM, 1 hit. PS00109 PROTEIN_KINASE_TYR, 1 ... IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR001245 Ser-Thr/Tyr_kinase_cat_dom ... IPR011009 Kinase-like_dom_sf. IPR000719 Prot_kinase_dom. IPR017441 Protein_kinase_ATP_BS. IPR001245 Ser-Thr/Tyr_kinase_cat_dom ...
View protein in InterPro. IPR011009 Kinase-like_dom_sf. IPR003527 MAP_kinase_CS. IPR000719 Prot_kinase_dom. ... View protein in InterPro. IPR011009 Kinase-like_dom_sf. IPR003527 MAP_kinase_CS. IPR000719 Prot_kinase_dom. ... Kinase, Serine/threonine-protein kinaseSAAS annotation. Automatic assertion according to rulesi ... PROSITE; a protein domain and family database. More...PROSITEi. View protein in PROSITE. PS01351 MAPK, 1 hit. PS50011 PROTEIN_ ...
... Susan Kretschmer sxk29 at po.CWRU.Edu Thu Apr 1 22:50:49 EST 1993 *Previous ... protein kinases retroviral insertion sequences oncogenes and anti-oncogenes (any available data) public domain software for mol ...
... Bernard Lassegue medbpl at emory.edu Fri Feb 16 13:46:11 EST 1996 *Previous message: Freeze/ ... I have started measuring in-situ Protein Kinase C activity in permeabilized cells grown in 96-well plates, based on a few ...
... is a highly specific substrate for DNA-PK, with the sequence Glu-Pro-Pro-Leu-Ser ... DNA-Dependent Protein Kinase. Purified kinase that phosphorylates several DNA-binding proteins in vitro, including p53. ... DNA-Dependent Protein Kinase. Purified kinase that phosphorylates several DNA-binding proteins in vitro, including p53. ... cAMP-Dependent Protein Kinase, Catalytic Subunit. Purified kinase for protein phosphorylation and signal transduction studies. ...
... is a truncated form of the v-AbI Protein Tyrosine Kinase, a partner in the Gag-Abl fusion protein of the Abelson murine ... 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 ... Abl Protein Tyrosine Kinase (AbI) is a truncated form of the v-AbI Protein Tyrosine Kinase, a partner in the Gag-Abl fusion ... NEBuffer™ for Protein Kinases (PK) -20 10 X Product Categories:. Discontinued Products. * Properties & Usage Unit Definition. ...
Protein Kinase A is directed to specific sub cellular locations after tethering to Protein kinase A anchoring proteins (AKAPs ... out of 540 different protein kinase genes that make up for human kinome, only one other protein kinase, Casein kinase 2, is ... "cAMP-dependent protein kinase" redirects here. It is not to be confused with AMP-activated protein kinase or cyclin-dependent ... Protein kinase A, more precisely known as adenosine 3,5-monophosphate (cyclic AMP)-dependent protein kinase was discovered by ...
DNA looping by Ku and the DNA-dependent protein kinase. Robert B. Cary, Scott R. Peterson, Jinting Wang, David G. Bear, E. ... DNA looping by Ku and the DNA-dependent protein kinase. Robert B. Cary, Scott R. Peterson, Jinting Wang, David G. Bear, E. ... DNA-dependent protein kinase;. DNA-PKcs,. DNA-PK catalytic subunit;. AFM,. atomic force microscopy;. EMSA,. electrophoretic ... DNA looping by Ku and the DNA-dependent protein kinase. Robert B. Cary, Scott R. Peterson, Jinting Wang, David G. Bear, E. ...
... Halyna M. Kuznietsova, Maryna S. Yena, Iryna P. Kotlyar ... "Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate," The Scientific World Journal, vol. 2016, Article ID ...
... Halyna M. Kuznietsova, Maryna S. Yena, Iryna P. Kotlyar ... In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4- ... Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD ...
  • siRNAs against PKCβII, dominant negative PKCβII and nonphosphorylatable mutant of PKCβII, PKCβIIS660A, blocked mTORC1 activity due to lack of PRAS40 phosphorylation, resulting in significant inhibition of HG-induced MC protein synthesis and hypertrophy. (omicsonline.org)
  • Two major factors influence activity of MAP kinases: a) signals that activate transmembrane receptors (either natural ligands or crosslinking agents) and proteins associated with them (mutations that simulate active state) b) signals that inactivate the phosphatases that restrict a given MAP kinase. (wikipedia.org)
  • Diaz-Meco MT, Municio MM, Sanchez P, Lozano J, Moscat J. Lambda-interacting protein, a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota and stimulates its kinase activity in vitro and in vivo. (springer.com)
  • This group represents protein kinase C (KPC), including zeta/iota types from mammals, protein kinase C-like 3 from round worms [ PMID: 9422779 ] and atypical protein kinase C (aPKC) from fruit flies [ PMID: 10995441 ]. (ebi.ac.uk)
  • Structure, expression, and properties of an atypical protein kinase C (PKC3) from Caenorhabditis elegans. (ebi.ac.uk)
  • Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. (ebi.ac.uk)
  • Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. (ebi.ac.uk)
  • Atypical protein kinase C{iota} is required for bronchioalveolar stem cell expansion and lung tumorigenesis. (ebi.ac.uk)
  • In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. (scivee.tv)
  • In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. (hindawi.com)
  • In Protein Kinase Protocols, a panel of highly skilled laboratory investigators describe both basic and more sophisticated methods for the analysis of kinase-mediated signaling cascades, with emphasis on the identification of proteins according to their interactive relationships and the analysis of their functional properties. (springer.com)
  • Select one or more mouse PIRSF members to download protein sequences or forward to NCBI BLAST. (jax.org)