An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
A 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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A 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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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).
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.
Agents that inhibit PROTEIN KINASES.
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.
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.
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.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A 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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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)
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
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)
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A 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 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.
Established cell cultures that have the potential to propagate indefinitely.
The rate dynamics in chemical or physical systems.
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.
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.
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.
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.
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 kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
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.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
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.
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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A 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.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
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.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
The 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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
A 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.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Proteins prepared by recombinant DNA technology.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A 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.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A 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.
The phosphoric acid ester of serine.
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.
Elements of limited time intervals, contributing to particular results or situations.
Compounds or factors that act on a specific enzyme to increase its activity.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
A 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)
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.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
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.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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.
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.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Transport proteins that carry specific substances in the blood or across cell membranes.
A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.
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.
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.
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.
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.
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.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A 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.
GLYCEROL esterified with FATTY ACIDS.
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.
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)
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.
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.
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
A cell line derived from cultured tumor cells.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
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.
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.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A 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.
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.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
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
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)
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 in which a polyacrylamide gel is used as the diffusion medium.
The sum of the weight of all the atoms in a molecule.
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)
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
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.
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.
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.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
A 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.
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.
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).
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)
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.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The phosphoric acid ester of threonine. Used as an identifier in the analysis of peptides, proteins, and enzymes.
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.
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.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
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
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
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).
Compounds with a core of fused benzo-pyran rings.
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.-.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
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.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A 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.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A 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.
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.
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.
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.
The nonstriated involuntary muscle tissue of blood vessels.
Four carbon unsaturated hydrocarbons containing two double bonds.
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
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
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.
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.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
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)
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.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
A 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.
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.
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.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
A 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).
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.
A group of compounds that contain the structure SO2NH2.
A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function.

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)

Dive into the research topics of p21(ras) function is important for T cell antigen receptor and protein kinase C regulation of nuclear factor of activated T cells. Together they form a unique fingerprint. ...
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:] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:] K05858 PLCB; phosphatidylinositol phospholipase C, beta [EC:] 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:] K19662 PRKCB; classical protein kinase C beta type [EC:] K19663 PRKCG; classical protein kinase C gamma type [EC:] K18050 PRKCE; novel protein kinase C epsilon type [EC:] K06070 PKD; protein kinase D [EC:] K06070 PKD; protein kinase D [EC:] K06070 PKD; protein ...
TY - JOUR. T1 - Selectivity of connexin 43 channels is regulated through protein kinase C-dependent phosphorylation. AU - Ek-Vitorin, Jose F.. AU - King, Timothy J.. AU - Heyman, Nathanael S.. AU - Lampe, Paul D.. AU - Burt, Janis M.. PY - 2006/6. Y1 - 2006/6. N2 - Coordinated contractile activation of the heart and resistance to ischemic injury depend, in part, on the intercellular communication mediated by Cx43-composed gap junctions. The function of these junctions is regulated at multiple levels (assembly to degradation) through phosphorylation at specific sites in the carboxyl terminus (CT) of the Cx43 protein. We show here that the selective permeability of Cx43 junctions is regulated through protein kinase C (PKC)-dependent phosphorylation at serine 368 (S368). Selective permeability was measured in several Cx43-expressing cell lines as the rate constant for intercellular dye diffusion relative to junctional conductance. The selective permeability of Cx43 junctions under control ...
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 ...
|strong|Mouse anti Human protein kinase C zeta antibody|/strong| recognizes the protein kinase C (PKC) zeta type also known as PKC2.|br||br|Protein kinase C zeta is a member of the PKC family of serin…
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 ...
using yeast to study the role of ceramide pathway in the regulation of mammalian protein kinase c isoforms dissertação de mestrado em genetica molecul
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 ...
wp-content/uploads/2018/08/johns_hopkins_medicine_logo-300-x-156-300x156.jpg 0 0 admin /wp-content/uploads/2018/08/johns_hopkins_medicine_logo-300-x-156-300x156.jpg admin2014-08-08 15:04:382018-08-11 11:48:32Phosphorylation of protein kinase C sites Ser42/44 decreases Ca(2+)-sensitivity and blunts enhanced length-dependent activation in response to protein kinase A in human cardiomyocytes ...
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
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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 - UR - 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 - Pipeline Review, H1 2017 Size and Share Published in 2017-05-30 Available for US$ 3500 at
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 ...
TY - JOUR. T1 - NMDA receptor blockade prevents the increase in protein kinase C substrate (protein F1) phosphorylation produced by long-term potentiation. AU - Linden, David J.. AU - Wong, Ka L.. AU - Sheu, Fwu Shan. AU - Routtenberg, Aryeh. PY - 1988/8/16. Y1 - 1988/8/16. N2 - Recent evidence has implicated activation of the N-methyl-d-aspartate (NMDA) class of glutamate receptor in the initiation of hippocampal long-term potentiation (LTP), an electrophysiological model of information storage in the brain. A separate line of evidence has suggested that activation of protein kinase C (PKC) and the consequent phosphorylation of it substrates is necessary for the maintenance of the LTP response. To determine if PKC activation is a consequence of NMDA receptor activation during LTP, we applied the NMDA receptor antagonist drug, dl-aminophosphonovalerate (APV) both immediately prior to and following high frequency stimulation, resulting in successful and unsuccessful blockade of LTP initiation, ...
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 - Properties of membrane-inserted Protein Kinase C. AU - Bazzi, Mohammad D.. AU - Nelsestuen, Gary L.. PY - 1988. Y1 - 1988. N2 - Protein kinase C (PKC) interacted with phospholipid vesicles in a calcium-dependent manner and produced two forms of membrane-associated PKC: a reversibly bound form and a membrane-inserted form. The two forms of PKC were isolated and compared with respect to enzyme stability, cofactor requirements, and phorbol ester binding ability. Membrane-inserted PKC was stable for several weeks in the presence of calcium chelators and could be rechromatographed on gel filtration columns in the presence of EGTA without dissociation of the enzyme from the membrane. The activity of membrane-inserted PKC was not significantly influenced by Ca2+, phospholipids, and/or PDBu. Partial dissociation of this PKC from phospholipid was achieved with Triton X-100, followed by dialysis to remove the detergent. The resulting free PKC appeared indistinguishable from original free ...
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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.]. ...
Translocation of PKC isoforms has been implicated in mechanisms involved in heart failure, 22myocardial hypertrophy, 23and preconditioning. PKC isoforms are activated by phosphorylating enzymes such as G proteins and are modified in enzyme activity by phospholipids, diacylglycerol, increased Ca2+, nitric oxide, and superoxide anions. This is followed by translocation in an isoform-specific and cytoskeleton-mediated manner to subcellular targets, which can be directly visualized by immunohistochemical methods. Only 10 min of ischemia 24or brief administrations of pharmacologic agents 11,25may elicit significant PKC translocation. Recent evidence indicates that translocation is dependent on PKC binding to a family of proteins called receptors of activated C kinase. 26These anchoring proteins are highly specific, and each PKC isoenzyme can bind to only one receptor of activated C kinase. Thus, different PKC isoforms may be linked to distinctive aspects of myocardial function, and this functional ...
The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, which plays crucial roles in synaptic plasticity and development. We have recently shown that potentiation of NMDA receptor function by protein kinase C (PKC) appears to be mediated via activation of non-receptor tyrosine kinases. The aim of this study was to test whether this effect could be mediated by direct tyrosine phosphorylation of the NR2A or NR2B subunits of the receptor. Following treatment of rat hippocampal CA1 mini-slices with 500 nM phorbol 12-myristate 13-acetate (PMA) for 15 min, samples were homogenized, immunoprecipitated with anti-NR2A or NR2B antibodies and the resulting pellets subjected to Western blotting with antiphosphotyrosine antibody. An increase in tyrosine phosphorylation of both NR2A (76 +/- 11% above control) and NR2B (41 +/- 11%) was observed. This increase was blocked by pretreatment with the selective PKC inhibitor chelerythrine, with the tyrosine kinase inhibitor Lavendustin A or with the
TY - JOUR. T1 - Unique functions for protein kinase D1 and protein kinase D2 in mammalian cells. AU - Matthews, Sharon A.. AU - Navarro, Maria N.. AU - Sinclair, Linda V.. AU - Emslie, Elizabeth. AU - Feijoo-Carnero, Carmen. AU - Cantrell, Doreen A.. PY - 2010/11/15. Y1 - 2010/11/15. N2 - Mammalian PKD (protein kinase D) isoforms have been implicated in the regulation of diverse biological processes in response to diacylglycerol and PKC (protein kinase C) signalling. To compare the functions of PKD1 and PKD2 in vivo, we generated mice deficient in either PKD1 or PKD2 enzymatic activity, via homozygous expression of PKD1(S744A/S7484) or PKD2(S707A/S711A) knockin alleles. We also examined PKD2-deficient mice generated using gene-trap technology. We demonstrate that, unlike PKD I, PKD2 catalytic activity is dispensable for normal embryogenesis. We also show that PKD2 is the major PKD isoform expressed in lymphoid tissues, but that PKD2 catalytic activity is not essential for the development of ...
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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 ...
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 …
Protein kinase C has been in the spotlight since the discovery two decades ago that it is activated by the lipid second messenger diacylglycerol. Despite protein kinase Cs enduring stage presence, the regulation and specific roles of its isozymes in defined cellular processes are still under intens …
|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, 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 ...
TY - JOUR. T1 - Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. AU - Kraft, A. S.. AU - Anderson, W. B.. AU - Cooper, H. L.. AU - Sando, J. J.. N1 - Copyright: Copyright 2004 Elsevier B.V., All rights reserved.. PY - 1982. Y1 - 1982. UR - UR - M3 - Article. C2 - 7142138. AN - SCOPUS:0020356002. VL - 257. SP - 13193. EP - 13196. JO - Journal of Biological Chemistry. JF - Journal of Biological Chemistry. SN - 0021-9258. IS - 22. ER - ...
MARCKS (myristoylated alanine-rich protein kinase C substrate), Authors: Atsuhiro Tanabe, Maho Saito. Published in: Atlas Genet Cytogenet Oncol Haematol.
Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase Cs (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK ...
Looking for online definition of Protein-kinase C-related kinase 2 in the Medical Dictionary? Protein-kinase C-related kinase 2 explanation free. What is Protein-kinase C-related kinase 2? Meaning of Protein-kinase C-related kinase 2 medical term. What does Protein-kinase C-related kinase 2 mean?
Ludwig, L.M.; Weihrauch, D.; Kersten, J.R.; Pagel, P.S.; Warltier, D.C., 2004: Protein kinase C translocation and Src protein tyrosine kinase activation mediate isoflurane-induced preconditioning in vivo: potential downstream targets of mitochondrial adenosine triphosphate-sensitive potassium channels and reactive oxygen species
As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 ± 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol ...
Protein kinase C is the Ca{dollar}\sp{lcub}2+{rcub}{dollar}/phospholipid-dependent enzyme that serves as the receptor for, and is directly activated by, the tumour-promoting phorbol esters. To examine the involvement of protein kinase C in the regulation of the organization or function of the actin-containing microfilaments, the activity of the enzyme towards two distinct groups of proteins that are thought to be involved in microfilament regulation has been investigated. For these studies, protein kinase C was partially purified from bovine brain or was more extensively purified from rat brain. Two proteins that are localized in certain areas of microfilament-membrane attachment (focal contacts), vinculin and talin, were identified as in vitro substrates for protein kinase C. Purified protein kinase C also phosphorylated chicken gizzard myosin light chain kinase and different forms of caldesmon, proteins that are involved in the regulation of contractile events. Chicken gizzard caldesmon and chicken
Protein kinase C beta II (PKCβII) has been implicated in diabetic nephropathy (DN). Mesangial cell (MC) hypertrophy is a pathologic feature of DN. PKCβII...
TY - JOUR. T1 - Protein kinase C effects on nerve function, perfusion, Na+,K+-ATPase activity and glutathione content in diabetic rats. AU - Cameron, Norman E. AU - Cotter, M A AU - Jack, A M AU - Basso, M D AU - Hohman, T C PY - 1999. Y1 - 1999. N2 - Aims/hypothesis. Increased protein kinase C activity has been linked to diabetic vascular complications in the retina and kidney, which were attenuated by protein kinase C antagonist treatment. Neuropathy has a vascular component, therefore, the aim was to assess whether treatment with WAY151003 or chelerythrine, inhibitors of protein kinase C regulatory and catalytic domains respectively, could correct nerve blood flow, conduction velocity, Na+,K+-ATPase, and glutathione deficits in diabetic rats.Methods. Diabetes was induced by streptozotocin. Sciatic nerve conduction velocity was measured in vivo and sciatic endoneurial perfusion was monitored by microelectrode polarography and hydrogen clearance. Glutathione content and Na+,K+-ATPase activity ...
TY - JOUR. T1 - Enzastaurin (LY317615), a protein kinase Cβ inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. AU - Rizvi, Mujahid A.. AU - Ghias, Kulsoom. AU - Davies, Katharine M.. AU - Ma, Chunguang. AU - Weinberg, Frank. AU - Munshi, Hidayatullah G.. AU - Krett, Nancy L.. AU - Rosen, Steven T.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2006/7. Y1 - 2006/7. N2 - Enzastaurin (LY317615), an acyclic bisindolylmaleimide, is an oral inhibitor of the protein kinase Cβ isozyme. The objective of this study was to assess the efficacy of enzastaurin in inducing apoptosis in multiple myeloma (MM) cell lines and to investigate possible mechanisms of apoptosis. Cell proliferation assays were done on a variety of MM cell lines with unique characteristics (dexamethasone sensitive, dexamethasone resistant, chemotherapy sensitive, and melphalan resistant). The dexamethasone-sensitive MM.1S cell line was used to further assess the effect ...
Atypical protein kinase C (PKC) isoforms play essential roles in lots of neural processes including synaptic plasticity and neurodegenerative diseases. the appearance of atypical PKCs in phrenic electric MRS 2578 motor neurons offers a construction within which to assess their function in respiratory electric motor control including book types of respiratory plasticity recognized to occur in this area. 2000 Provided their function in synaptic plasticity we questioned whether atypical PKCs can be found in the phrenic electric motor nucleus an integral site for respiratory electric motor plasticity (Mitchell proteins expression thats diminished as well as non-existent (e.g. Sanders and Ridyard 2000 Cell lifestyle circumstances change from the surroundings potentially resulting in altered proteins appearance. The strength of labeling within phrenic electric motor neurons described right here shows that atypical PKC isoforms possess the to be engaged in essential neuron-specific functions like the ...
RESULTS: Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly ...
TY - JOUR. T1 - Expression of amyloid beta peptide in human platelets. T2 - Pivotal role of the phospholipase Cγ2-protein kinase C pathway in platelet activation. AU - Shen, Ming Yi. AU - Hsiao, George. AU - Fong, Tsorng Han. AU - Chou, Duen Suey. AU - Sheu, Joen Rong. PY - 2008/2. Y1 - 2008/2. N2 - The amyloid β peptide (Aβ), a mediator of neuronal and vascular degeneration in the pathogenesis of Alzheimers disease and cerebral amyloid angiopathy may have peripheral actions. Platelets are enriched with Aβ and have been shown to enhance platelet actions. However, the detailed signaling pathways through which Aβ activates platelets have not been previously explored. In this study, we examined the intra-platelet Aβ distribution using a gold labeling technique and noted that Aβ was predominantly localized in the cytoplasm of resting platelets. A marked increase in Aβ-gold labeling in an open canalicular system was observed in collagen-activated platelets. Exogenous Aβ (2-10 μM) ...
BACKGROUND: Titin is a giant protein crucial for the assembly and elasticity of the sarcomere. Recently, titin has been linked to signal transduction through its kinase domain, which has been proposed to sense mechanical load. We developed a knockout in which expression of M-line-deficient titin can be induced in adult mice and investigated the role of the titin kinase region in cardiac function. METHODS AND RESULTS: Isolated heart experiments revealed that in titin M-line-deficient mice, the contractile response to beta-adrenergic agonists and extracellular calcium is reduced. However, the Ca(2+) sensitivity and cooperativity of activation of skinned cardiac muscle were unchanged. In knockout mice, calcium transients showed a reduced rate of calcium uptake, and expression analysis showed reduced levels of calmodulin, phospholamban, and SERCA2. Ultimately, knockout mice developed cardiac hypertrophy and heart failure, which involves protein kinase C signal transduction but not the ...
TY - JOUR. T1 - Amelioration of denervation-induced atrophy by clenbuterol is associated with increased PKC-alpha activity. AU - Sneddon, Alan Arthur. AU - Delday, Margaret Inkster. AU - Maltin, Charlotte. PY - 2000/7. Y1 - 2000/7. N2 - Rat soleus muscle was denervated for 3 or 7 days, and total membrane protein kinase C (PKC) activity and translocation and immunocytochemical localization of PKC isoforms were examined. Dietary administration of clenbuterol concomitant with denervation ameliorated the atrophic response and was associated with increased membrane PKC activity at both 3 (140%) and 7 (190%) days. Of the five PKC isoforms (alpha, epsilon, theta, zeta, and mu) detected in soleus muscle by Western immunoblotting, clenbuterol treatment affected only the PKC-alpha and PKC-theta forms. PKC-alpha was translocated to the membrane fraction upon denervation, and the presence of clenbuterol increased membrane-bound PKC-alpha and active PKC-alpha as assayed by Ser(657) phosphorylation. PKC-theta ...
Sugita M., Kuwata H., Kudo I., Hara S.. Protein kinase C (PKC) is a family of serine/threonine kinases involved in various signal transduction pathways. We investigated the roles of PKC in the regulation of group IIA secreted phospholipase A(2) (sPLA(2)-IIA) expression in cytokine-stimulated rat fibroblastic 3Y1 cells. Here we show that the induction of sPLA(2)-IIA by proinflammatory cytokines was under the control of both classical cPKCalpha and atypical aPKClambda/iota pathways by using PKC inhibitors, a PKC activator, and PKC knockdowns. Treatment of 3Y1 cells with PKC selective inhibitors having broad specificity, such as chelerythrine chloride and GF109203X, blocked IL-1beta/TNFalpha-dependent induction of sPLA(2)-IIA protein in a dose-dependent manner. Treatment with the PKC activator phorbol 12-myristate 13-acetate (PMA), which activates cPKC and novel nPKC isoforms, markedly attenuated the cytokine-dependent induction of sPLA(2)-IIA expression. In comparison, 24-h pretreatment with PMA, ...
1. Huang KP, Huang FL, Jager T, Li J, Reymann KG, Balschun D. Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling. J Neurosci. 2004;24:10660-10669 2. Baudier J, Deloulme JC, Van Dorsselaer A, Black D, Matthes HW. Purification and characterization of a brain-specific protein kinase C substrate, neurogranin (p17). Identification of a consensus amino acid sequence between neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain. J Biol Chem. 1991;266:229-237 3. Sheu FS, Mahoney CW, Seki K, Huang KP. Nitric oxide modification of rat brain neurogranin affects its phosphorylation by protein kinase C and affinity for calmodulin. J Biol Chem. 1996;271:22407-22413 4. Cohen RW, Margulies JE, Coulter PM 2nd, Watson JB. Functional consequences of expression of the neuron-specific, protein kinase C substrate RC3 (neurogranin) in Xenopus oocytes. Brain Res. 1993;627:147-152 5. Yang HM, ...
Global Markets Directs, Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC - Pipeline Review, provides in depth analysis on Protein Kinase C Epsilon Type (nPKC Epsilon or PRKCE or EC targeted pipeline therapeutics.
TY - JOUR. T1 - Phase I trial of high-dose tamoxifen in combination with cisplatin in patients with lung cancer and other advanced malignancies. AU - Perez, Edith A.. AU - Gandara, David R.. AU - Edelman, Martin J.. AU - ODonnell, Robert. AU - Lauder, Ignacio J.. AU - DeGregorio, Michael. PY - 2003/3/18. Y1 - 2003/3/18. N2 - Background. Tamoxifen has been reported to enhance the antitumor activity of cisplatin in preclinical models by modulation of protein kinase C signal transduction and apoptosis-related pathways. Methods. We conducted a phase I study of high-dose oral tamoxifen in combination with intravenous cisplatin, with two objectives: 1) to determine tolerability, and 2) to determine the daily tamoxifen dose required to achieve serum levels equivalent to in vitro concentrations reported to enhance cisplatin cytotoxicity in preclinical models. Tamoxifen was administered days one through seven at escalating daily doses of 160mg/m2 (n = 5), 200mg/m2 (n = 6), and 250 mg/m2 (n = 4) by ...
The Ca2+-insensitive protein kinase C (PKC) isoforms ε, η, δ and ζ are possible direct downstream targets of phosphatidylinositol 3-kinase (PI3-K), and might therefore be involved in insulin signalling. Although isoform-specific changes in PKC expression have been reported for skeletal muscle and liver in insulin-resistant states, little is known about these isoforms in adipocytes. Therefore we studied (1) expression and subcellular localization of these isoforms in murine adipocytes, (2) translocation of specific isoforms to membranes in response to treatment with insulin and phorbol 12-myristate 13-acetate (PMA) and (3) regulation of expression in insulin-resistant states. The PKC isoforms ε, η, δ and ζ are expressed in adipocytes. Immunoreactivity for all isoforms is higher in the membranes than in the cytosol, but subcellular fractionation by differential centrifugation shows an isoform-specific distribution within the membrane fractions. PMA treatment of adipocytes induces ...
Previous studies have shown that activators of protein kinase C (C kinase) produce synaptic potentiation in the hippocampus. For example, the C kinase activator phorbol dibutyrate has been shown to increase transmitter release in the hippocampus. In addition, a role for C kinase in long-term potentiation has been proposed. A common assumption in such studies has been that substrates for C kinase were responsible for producing these forms of synaptic potentiation. However, we have recently shown that phorbol dibutyrate increased the phosphorylated of synapsin II (formerly protein III, Browning et al., 1987) in chromaffin cells (Haycock et al., 1988). Synapsin II is a synaptic vesicle-associated phosphoprotein that is a very poor substrate for C kinase but an excellent substrate for cAMP-dependent and Ca2+/calmodulin-dependent protein kinase. We felt, therefore, that activation of C kinase might lead to activation of a kinase cascade. Thus effects of C kinase activation might be produced via the
TY - JOUR. T1 - The min K channel underlies the cardiac potassium current I(Ks) and mediates species-specific responses to protein kinase C. AU - Varnum, M. D.. AU - Busch, A. E.. AU - Bond, C. T.. AU - Maylie, J.. AU - Adelman, J. P.. PY - 1993. Y1 - 1993. N2 - A clone encoding the guinea pig (gp) min K potassium channel was isolated and expressed in Xenopus oocytes. The currents, gpI(sK), exhibit many of the electrophysiological and pharmacological properties characteristic of gpI(Ks), the slow component of the delayed rectifier potassium conductance in guinea pig cardiac myocytes. Depolarizing commands evoke outward potassium currents that activate slowly, with time constants on the order of seconds. The currents are blocked by the class III antiarrhythmic compound clofilium but not by the sotalol derivative E4031 or low concentrations of lanthanum. Like I(Ks) in guinea pig myocytes, gpI(sK) is modulated by stimulation of protein kinase A and protein kinase C (PKC). In contrast to rat and ...
TY - JOUR. T1 - Phosphorylation of MYPT1 by protein kinase C attenuates interaction with PP1 catalytic subunit and the 20 kDa light chain of myosin. AU - Tóth, Attila. AU - Kiss, Enikö. AU - Gergely, P.. AU - Walsh, Michael P.. AU - Hartshorne, David J.. AU - Erdődi, F.. PY - 2000/11/3. Y1 - 2000/11/3. N2 - The effect of phosphorylation in the N-terminal region of myosin phosphatase target subunit 1 (MYPT1) on the interactions with protein phosphatase 1 catalytic subunit (PP1c) and with phosphorylated 20 kDa myosin light chain (P-MLC20) was studied. Protein kinase C (PKC) phosphorylated threonine-34 (1 mol/mol), the residue preceding the consensus PP1c-binding motif (35KVKF38) in MYPT11-38, but this did not affect binding of the peptide to PP1c. PKC incorporated 2 mol P(i) into MYPT11-296 suggesting a second site of phosphorylation within the ankyrin repeats (residues 40-296). This phosphorylation diminished the stimulatory effect of MYPT11-296 on the P-MLC20 phosphatase activity of PP1c. ...
This study demonstrates that different PKC isoforms are differentially expressed in particular cellular components of ovarian follicles of pre-pubertal, pubertal and adult mouse ovaries.. Data obtained from H-Score evaluation of immunohistochemistry findings revealed that PKCα expression was more apparent in oocytes of all follicles in pre-pubertal, pubertal and adult ovaries, though it was also expressed in granulosa cells. Interestingly, in adult and pre-pubertal ovaries, intense immunostaining of PKCα in oocytes was statistically significant in primordial (PND60, PND7 and PND1), primary (PND60, PND7 and PND1) and secondary follicles (PND60 and PND7), whereas in PND21 ovaries only oocytes of primordial follicles had significantly higher immunostaining level of PKCα. These findings support the idea that PKCα expression in oocytes of larger follicles may have low significance due to granulosa-oocyte interactions during initiation of hormone dependent follicular growth [27],[28]. PKCα ...
We isolated a group of genes that are rapidly and transiently induced in 3T3 cells by tetradecanoyl phorbol acetate (TPA). These genes are called TIS genes (for TPA-inducible sequences). Epidermal growth factor (EGF), fibroblast growth factor (FGF), and TPA activated TIS gene expression with similar induction kinetics. TPA pretreatment to deplete protein kinase C activity did not abolish the subsequent induction of TIS gene expression by epidermal growth factor or fibroblast growth factor; both peptide mitogens can activate TIS genes through a protein kinase C-independent pathway(s). We also analyzed TIS gene expression in three TPA-nonproliferative variants (3T3-TNR2, 3T3-TNR9, and A31T6E12A). The results indicate that (i) modulation of a TPA-responsive sodium-potassium-chloride transport system is not necessary for TIS gene induction either by TPA or by other mitogens and (ii) TIS gene induction is not sufficient to guarantee a proliferative response to mitogenic stimulation. ...
TY - JOUR. T1 - Monoclonal antibody analysis of phosphatidylserine and protein kinase C localizations in developing rat cerebellum. AU - Miyazawa, Atsuo. AU - Inoue, Hiroko. AU - Yoshioka, Tohru. AU - Horikoshi, Tetsuro. AU - Yanagisawa, Keiji. AU - Umeda, Masato. AU - Inoue, Keizo. PY - 1992/10. Y1 - 1992/10. N2 - Understanding the topographical relationships between phosphatidylserine (PS) and protein kinase C (PKC) within neurons can provide clues about the mechanism of translocation and activation of PKC. For this purpose we applied monoclonal antibodies (Abs) of PS and PKC to sections of developing rat cerebellum. The anti-PKC Ab immunohistochemical pattern showed homogeneous staining of Purkinje cells over various postnatal ages, whereas the anti-PS Ab staining showed a heterogeneous localization over these ages. Purkinje cells did not stain well between postnatal day 14 (PND 14) and PND 21, suggesting that the PS was lost from the membrane during preparation of the sections during this ...
Human UC11 astrocytoma cells were used to investigate the role of protein kinase C (PKC) and other kinases in neurokinin (NK)1 receptor desensitization. The selective NK1 receptor agonist [Sar9,Met(O2)11]-substance P stimulated a biphasic accumulation of [3H]inositol phosphates ([3H]IPs) in the presence of 10 mM LiCl in cells that had been prelabeled with [3H]inositol. An initial rapid phase of [3H]IP accumulation during the first 1 min was followed by a slower sustained phase for up to 90 min. These results demonstrate that the human NK1 receptor desensitizes rapidly but only partially. The selective PKC inhibitor Ro31-8220 did not prevent rapid NK1 receptor desensitization but after a longer incubation significantly potentiated human NK1 receptor agonist-stimulated accumulation of [3H]IPs. These results suggest that, although PKC does not mediate the process of rapid desensitization, it does have an inhibitory role at later times. This conclusion is supported by studies with staurosporine, ...
Dynamic changes of glycolipid domains within the plasma membranes of cultured rat cerebellar granule cells have been investigated. For this purpose, a pyrene-labelled derivative of G(M1) ganglioside has been incorporated in the cell plasma membrane, and the rate of excimer formation, directly related to the formation of domains, has been studied by a fluorescence imaging technique (excimer-formation imaging). Fluorescence imaging showed that upon addition of 100 μM glutamate, indirectly inducing the activation of protein kinase C (PKC), glycolipid concentration within domains increases in cell bodies. Comparable effects were exerted by the addition of PMA, directly inducing the activation of PKC. On the contrary, the phorbol ester was not effective in the presence of the specific PKC inhibitor, bisindolylmaleimide. These results suggest that glycolipid-enriched domains are dynamic supramolecular structures affected by membrane-associated events, such as PKC activation. Dynamic changes of ...
0033] In embodiments in which it is desirous to inhibit Hh pathway signaling, a cell is contacted with an aPKC iota antagonist. By an aPKC iota antagonist, it is meant an agent that reduces, suppresses or inhibits aPKC iota activity. In other words, an aPKC iota antagonist antagonizes the activating effect of aPKC iota on the Hh signaling pathway. In some embodiments, the aPKC iota antagonist is a polypeptide or peptide. For example, the antagonist may be a peptide that competes with natural substrates for access to the active site of aPKC iota, i.e. a pseudosubstrate inhibitor, or PSI. In some instance, the PSI is a PSI that is specific for atypical PKCs, i.e. it is specific for aPKC iota and aPKC zeta. In some instances, it is specific for aPKC iota. In some instances, the PSI is a peptide that consists or consists essentially of the sequence SIYRRGARRWRKLY (SEQ ID NO:4), for example a SIYRRGARRWRKLY peptide that has been myristoylated (to make it cell permeable). By consisting essentially ...
BioAssay record AID 163866 submitted by ChEMBL: Inhibition of [3H]- PDBu binding to peptide D of mouse skin Protein kinase C eta (inactive).
2 Department of Radiation Oncology, University Hospital Zurich, CH-8091 Zurich, Switzerland [S. R., C. G., S. B., M. P.]; Laboratory for Biochemistry, Federal Institute of Technology, 8091 Zurich, Switzerland [S. R., K. W.]; Novartis Pharma Inc., 4002 Basel, Switzerland [D. F.]; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 [M. S. S., S. W. L.] Abstract. Caspases are a family of cysteine proteases that constitute the apoptotic cell death machinery. We report the importance of the cytochrome c-mediated caspase-9 death pathway for radiosensitization by the protein kinase C (PKC) inhibitors staurosporine (STP) and PKC-412. In our genetically defined tumor cells, treatment with low doses of STP or the conventional PKC-specific inhibitor PKC-412 in combination with irradiation (5 Gy) potently reduced viability, enhanced mitochondrial cytochrome c release into the cytosol, and specifically stimulated the initiator caspase-9. Whereas treatment with each agent alone had a minimal ...
TY - JOUR. T1 - NF-κB/RelA transactivation is required for atypical protein kinase Cl-mediated cell survival. AU - Lu, Ying. AU - Jamieson, Lee. AU - Brasier, Allan R.. AU - Fields, Alan P.. PY - 2001/8/9. Y1 - 2001/8/9. N2 - In chronic myelogenous leukemia (CML), the oncogene bcr-abl encodes a dysregulated tyrosine kinase that inhibits apoptosis. We showed previously that human erythroleukemia K562 cells are resistant to antineoplastic drug (taxol)-induced apoptosis through the atypical protein kinase C iota isozyme (PKCl), a kinase downstream of Bcr-Abl. The mechanism(s) by which PKCl mediates cell survival to taxol is unknown. Here we demonstrate that PKCl requires the transcription factor nuclear factor-κB (NF-κB) to confer cell survival. At apoptosis-inducing concentrations, taxol weakly induces IκBα proteolysis and NF-κB translocation in K562 cells, but potently induces its transcriptional activity. Inhibition of NF-κB activity (by blocking IκBα degradation) significantly ...
c-Abl and Atm have been implicated in cell responses to DNA damage and oxidative stress. However, the molecular mechanisms by which they regulate oxidative stress response remain unclear. In this report, we show that deficiency of c-Abl and deficiency of ATM differentially altered cell responses to oxidative stress by induction of antioxidant protein peroxiredoxin I (Prx I) via Nrf2 and cell death, both of which required protein kinase C (PKC) δ activation and were mediated by reactive oxygen species. c-abl-/- osteoblasts displayed enhanced Prx I induction, elevated Nrf2 levels, and hypersusceptibility to arsenate, which were reinstated by reconstitution of c-Abl; Atm-/- osteoblasts showed the opposite. These phenotypes correlated with increased PKC δ expression in c-abl-/- osteoblasts and decreased PKC δ expression in Atm-/- cells, respectively. The enhanced responses of c-abl-/- osteoblasts could be mimicked by overexpression of PKC δ in normal cells and impeded by inhibition of PKC δ, and
sn-1,2-Didecanoylglycerol, a synthetic lipid second messenger and model diacylglycerol, was evaluated as a complete skin tumor promoter in CD-1 mice. In addition, sn-1,2-dioctanoylglycerol, sn-1,2-didecanoylglycerol, the second stage tumor promoter mezerein, and the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined for their ability to stimulate epidermal protein kinase C activity in vitro. All four compounds stimulated epidermal protein kinase C activity utilizing lysine-rich histone as the phosphate acceptor substrate. sn-1,2-Dioctanoylglycerol and sn-1,2-didecanoylglycerol stimulated epidermal protein kinase C activity to a maximum velocity similar to that obtained when the enzyme was stimulated with TPA; however, about 1000 times greater concentration of the sn-1,2-diacylglycerols was required. sn-1,2-Didecanoylglycerol was evaluated as a complete skin tumor promoter in CD-1 mice utilizing a dosing regimen demonstrated to produce epidermal hyperplasia. Mice ...
Insulin stimulated protein synthesis in L6 myoblasts but did not increase the labelling of DAG or the release of phosphocholine from phosphatidylcholine. The DAG lipase inhibitor, RHC 80267, more than doubled the amount of label appearing in DAG but did not stimulate protein synthesis. Even in the presence of the DAG lipase inhibitor insulin failed to have any effect on DAG labelling, and conversely RHC 80267 did not modify the insulin-induced increase in protein synthesis. These results suggest that endogenous DAG production is not involved in the stimulation of protein synthesis by insulin. However, exogenous diacylglycerols (1-oleoyl-2-acetyl glycerol and 1-stearoyl-2-arachidonoyl glycerol) both stimulated protein synthesis in L6 myoblasts. The efficacy of the former (arachidonatefree) DAG suggested that their action was by activation of protein kinase C rather than by arachidonate release and prostaglandin formation. Ibuprofen, an inhibitor of cyclo-oxygenase failed to block the effects of ...
TY - JOUR. T1 - PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia. AU - Mashukova, Anastasia. AU - Forteza, Radia. AU - Wald, Flavia A.. AU - Salas, Pedro J. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Phosphorylation of the activation domain of protein kinase C (PKC) isoforms is essential to start a conformational change that results in an active catalytic domain. This activation is necessary not only for newly synthesized molecules, but also for kinase molecules that become dephosphorylated and need to be refolded and rephosphorylated. This rescuemechanism is responsible for the maintenance of the steady-state levels of atypical PKC (aPKC [PKCι/λ and ζ]) and is blocked in inflammation. Although there is consensus that phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized molecules, it is unclear what kinase performs that function during the rescue and where ...
1. The involvement of phospholipase D (PLD) in the 5-hydroxytryptamine 5-HT1B/5-HT1D-signalling pathway was assessed in the rabbit isolated mesenteric artery. 2. RT-PCR analysis of mesenteric smooth muscle cells revealed a strong signal corresponding to mRNA transcript for the 5-HT1B receptor. The PCR fragment corresponded to the known sequence for the 5-HT1B receptor. No signal corresponding to 5-HT1D mRNA was detected. 3. Neither 5-HT (3 microM) nor KCl (45 mM) individually stimulated any significant increase in the smooth muscle concentration of [33P]-PtdBut to reflect PLD activity. However, in the presence of KCl (45 mM), 5-HT evoked a concentration-dependent increase in [33P]-PtdBut, to a maximum of 84% with 5-HT (3 microM). 4. [33P]-PtdBut accumulation evoked by 5-HT in the presence of KCl was abolished in nominally calcium-free Krebs-Henseleit Buffer (KHB) or with the selective protein kinase C inhibitor, Ro-31 8220 (10 microM, 20 min). 5. 5-HT (3 microM) in the presence of KCl (45 mM) failed to
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Objective: An increase in intracellular calcium concentration ([Ca2+]i) leads to augmentation of late sodium current (late INa) by activating Ca2+-calmodulin-dependent protein kinase II (CaMK-II). The objective of this study was to confirm our hypothesis that both CaMK-II and protein kinase C (PKC) are the signaling molecules whose activation result in increased late INa in the presence of an increased [Ca2+]i.. Methods: Whole-cell and open-cell patch clamp techniques were used to record late INa in rabbit ventricular myocytes dialyzed with pipette solutions containing various concentrations (0.1, 0.3 and 0.6 μM) of [Ca2+]i in the absence and presence of CaMK-II (KN-93), PKC (bisindolylmaleimide, Bim) and MAPK (U0126) inhibitors in the bath solution.. Results: Increases in [Ca2+]i from 0.1 to 0.6 μM resulted in an augmentation of late INa from 0.30 ± 0.03 to 0.45 ± 0.03 pA/pF (n=8-10, p,0.01) in a concentration dependent manner, which was associated with an increase in mean Na+ channel open ...
Pro-apoptotic protein kinase C delta is associated with intranuclear inclusions in a transgenic model of Huntingtons disease.: In order to investigate any effe
In this paper, we have shown that specific isoforms of PKC are pivotal intracellular mediators of signals that regulate the production of rod photoreceptors in the postnatal mouse retina. The complete lack of rods detected in the presence of PKC inhibitors suggests that this enzyme may play this key role for the wide variety of other signals that can elicit rod production.. To provide access to factors that might modulate rod photoreceptor formation, we made use of a well-characterized explant culture system that we developed and have used in many studies of retinal development (Sparrow et al., 1990; Zhao et al., 1995; Zhang et al. 2002, 2004, 2005). These cultures maintain excellent cell viability, tissue lamination, and cell differentiation. In a microarray analysis of gene expression in vivo and in explant cultures, we did, however, find that expression of some genes is delayed by 1-2 d (Liu et al., 2008). This is apparent in the low levels of opsin expression in 4 d explant cultures from P1 ...
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.
TY - JOUR. T1 - Rottlerin inhibits tonicity-dependent expression and action of TonEBP in a PKCδ-independent fashion. AU - Zhao, Hongyu. AU - Tian, Wei. AU - Cohen, David M.. PY - 2002. Y1 - 2002. N2 - Novel protein kinase C (PKC) isoforms PKCδ and PKCε have recently been implicated in signaling by hypertonic stress. We investigated the role of the putative PKCδ inhibitor rottlerin on tonicity-dependent gene regulation. In the renal medullary mIMCD3 cell line, rottlerin blocked tonicity-dependent transcription of a tonicity enhancer (TonE)-driven luciferase reporter gene, as well as tonicity-dependent transcription of the physiological tonicity effector gene aldose reductase, but not urea-dependent transcription. Consistent with these data, rottlerin inhibited tonicity-dependent expression of TonE binding protein (TonEBP) at the mRNA and protein levels. Another inhibitor of both novel and conventional PKC isoforms, GF-109203X, suppressed TonEBP-dependent transcription but failed to influence ...
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors.[6]. ...
Protein kinase Cepsilon (PKCε) exerts a well-known cardio-protective activity in ischemia-reperfusion injury and plays a pivotal role in stem cell proliferation and differentiation. Although many studies have been performed on physiological and morphological effects of PKCε mis-expression in cardiomyocytes, molecular information on the role of PKCε on early cardiac gene expression are still lacking. We addressed the molecular role of PKCε in cardiac cells using mouse cardiomyocytes and rat bone marrow mesenchymal stem cells. We show that PKCε is modulated in cardiac differentiation producing an opposite regulation of the cardiac genes NK2 transcription factor related, locus 5 (nkx2.5) and GATA binding protein 4 (gata4) both in vivo and in vitro. Phospho-extracellular regulated mitogen-activated protein kinase 1/2 (p-ERK1/2) levels increase in PKCε over-expressing cells, while pkcε siRNAs produce a decrease in p-ERK1/2. Indeed, pharmacological inhibition of ERK1/2 rescues the expression ...
One very important group of protein kinases are the MAP kinases (acronym from: "mitogen-activated protein kinases"). Important ... Hanks SK, Hunter T (May 1995). "Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain ... Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and ... A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation ...
... (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase ( ... Myotonin-protein kinase is a serine-threonine kinase that is closely related to other kinases that interact with members of the ... Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase composed of a kinase domain and a coiled-coil domain ... The dmpk gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases and Rho kinase family. Data ...
... may refer to: Histidine kinase, an enzyme Protein-histidine tele-kinase, an enzyme Protein-histidine ... pros-kinase, an enzyme This disambiguation page lists articles associated with the title Protein histidine kinase. If an ... Look up protein kinase in Wiktionary, the free dictionary. ...
The protein kinase domain is a structurally conserved protein domain containing the catalytic function of protein kinases. ... Hanks SK, Hunter T (May 1995). "Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain ... Protein kinase function has been evolutionarily conserved from Escherichia coli to Homo sapiens. Protein kinases play a role in ... Protein kinases are a group of enzymes that move a phosphate group onto proteins, in a process called phosphorylation. This ...
It should not be confused with 5'-AMP-activated protein kinase (AMP-activated protein kinase). Protein kinase A, more precisely ... Protein kinase Signal transduction G protein-coupled receptor Serine/threonine-specific protein kinase Myosin light-chain ... out of 540 different protein kinase genes that make up the human kinome, only one other protein kinase, casein kinase 2, is ... Protein kinase A acts to phosphorylate many enzymes important in metabolism. For example, protein kinase A phosphorylates ...
A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases ... the tyrosine kinases act on tyrosine, and a number (dual-specificity kinases) act on all three. There are also protein kinases ... and protein kinase inhibitors can be used to treat diseases due to hyperactive protein kinases (including mutant or ... PMID 34354255 A list of US FDA-approved small molecule protein kinase inhibitors, their protein kinase targets, therapeutic ...
... including integrin-linked kinase (ILK) and mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK2) can also ... Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases ... For example, PI 3-kinases may be activated by a G protein coupled receptor or receptor tyrosine kinase such as the insulin ... There are three different genes that encode isoforms of Protein kinase B. These three genes are referred to as AKT1, AKT2, and ...
The protein encoded by this gene belongs to the protein kinase C superfamily. This kinase is activated by Rho family of small G ... "A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase ... "A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta ... This kinase can be activated by phospholipids and by limited proteolysis. The 3-phosphoinositide dependent protein kinase-1 ( ...
... protein tau kinase, STK31, tau kinase, [tau-protein] kinase, tau-protein kinase I, tau-protein kinase II, tau-tubulin kinase, ... Human genes encoding proteins with Tau-protein kinase activity include: BRSK1 BRSK2 GSK3A GSK3B Ishiguro K, Ihara Y, Uchida T, ... In enzymology, a tau-protein kinase (EC is an enzyme that catalyzes the chemical reaction ATP + tau protein ⇌ {\ ... Other names in common use include ATP:tau-protein O-hosphotransferase, brain protein kinase PK40erk, cdk5/p20, CDK5/p23, ...
Serine/threonine-protein kinase D1 is an enzyme that in humans is encoded by the PRKD1 gene. Members of the protein kinase D ( ... "The pleckstrin homology domain of protein kinase D interacts preferentially with the eta isoform of protein kinase C". J. Biol ... Holmes AM (1996). "In vitro phosphorylation of human immunodeficiency virus type 1 Tat protein by protein kinase C: evidence ... "Bruton's tyrosine kinase (Btk) associates with protein kinase C mu". FEBS Lett. 461 (1-2): 68-72. doi:10.1016/s0014-5793(99) ...
... membrane-bound receptor for activated protein kinase C proteins). The protein kinase C enzymes are known for their long-term ... In cell biology, Protein kinase C, commonly abbreviated to PKC (EC, is a family of protein kinase enzymes that are ... The consensus sequence of protein kinase C enzymes is similar to that of protein kinase A, since it contains basic amino acids ... Serine/threonine-specific protein kinase Signal transduction Yasutomi Nishizuka, discovered protein kinase C Ccdc60 Wilson CH, ...
... NA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein ... Patel RC, Sen GC (August 1998). "PACT, a protein activator of the interferon-induced protein kinase, PKR". The EMBO Journal. 17 ... September 2012). "Induction of dsRNA-activated protein kinase links mitochondrial unfolded protein response to the pathogenesis ... "The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient ...
... histidine kinase, histidine protein kinase, protein histidine kinase, protein kinase (histidine), and HK3. Fujitaki JM, Fung G ... In enzymology, a protein-histidine tele-kinase (EC is an enzyme that catalyzes the chemical reaction ATP + protein L- ... protein-histidine kinases). The systematic name of this enzyme class is ATP:protein-L-histidine Ntau-phosphotransferase. Other ... the two substrates of this enzyme are ATP and protein L-histidine, whereas its two products are ADP and protein Ntau-phospho-L- ...
... , also known as B lymphocyte kinase, is a non-receptor tyrosine kinase that in humans is encoded by ... microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase". Mol. Cell. Biol. 13 (9): ... It is of the Src family of tyrosine kinases. The tyrosine-protein kinase BLK has been shown to interact with UBE3A. ... 1993). "Mapping of sites on the Src family protein tyrosine kinases p55blk, p59fyn, and p56lyn which interact with the effector ...
The Raf kinase inhibitor protein (RKIP) is a kinase inhibitor protein, that regulates many signaling pathways within the cell. ... RKIP has also been shown to inhibit G protein coupled receptor kinases (GRK) when phosphorylated by protein kinase C. Via this ... Lorenz K, Lohse MJ, Quitterer U (2003): Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature 426: 574 ... Odabaei, G.; Chatterjee, D.; Jazirehi, A. R.; Goodglick, L.; Yeung, K.; Bonavida, B. (2004). "Raf-1 Kinase Inhibitor Protein: ...
... ketosamine 3-kinase 2, fructosamine-3-kinase-related protein, ribulosamine/erythrulosamine 3-kinase, ribulosamine 3-kinase) is ... Protein-ribulosamine 3-kinase (EC, FN3KRP, FN3K-related protein, FN3K-RP, ... "A mammalian protein homologous to fructosamine-3-kinase is a ketosamine-3-kinase acting on psicosamines and ribulosamines but ... Protein-ribulosamine+3-kinase at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC 2.7.1) ...
... or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP ... EC Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System cGMP-Dependent+Protein+Kinases at the US ... suppression of the kinase activity in the absence of cGMP, and interactions with other proteins including protein substrates (2 ... Protein pages needing a picture, Genes on human chromosome 4, Protein kinases, EC 2.7.11). ...
Protein kinase C and Rho-associated protein kinase are involved in regulating calcium ion intake; these calcium ions, in turn ... DMPK-related cell division control protein 42 (Cdc42)-binding kinases (MRCK) and citron kinase. All of these kinases are ... Rho-associated protein kinase (ROCK) is a kinase belonging to the AGC (PKA/ PKG/PKC) family of serine-threonine specific ... Rho-associated protein kinase are serine or threonine kinases that determine the calcium sensitivity in smooth muscle cells. ...
... , also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the SYK gene. SYK ... "Entrez Gene: SYK Spleen tyrosine kinase". Chan AC, Iwashima M, Turck CW, Weiss A (November 1992). "ZAP-70: a 70 kd protein- ... Sada K, Minami Y, Yamamura H (September 1997). "Relocation of Syk protein-tyrosine kinase to the actin filament network and ... Roskoski R (2016). "Ibrutinib inhibition of Bruton protein-tyrosine kinase (BTK) in the treatment of B cell neoplasms". ...
... histidine kinase, histidine protein kinase, protein histidine kinase, protein kinase (histidine), and HK2. Fujitaki JM, Fung G ... In enzymology, a protein-histidine pros-kinase (EC is an enzyme that catalyzes the chemical reaction ATP + protein L- ... protein-histidine kinases). The systematic name of this enzyme class is ATP:protein-L-histidine Npi-phosphotransferase. Other ... the two substrates of this enzyme are ATP and protein L-histidine, whereas its two products are ADP and protein Npi-phospho-L- ...
The A-kinase anchoring proteins or A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have ... AKAPs act as scaffold proteins wherein they bind PKA and other signaling proteins and physically tether these multi-protein ... Marin, Wenwen (January 2020). "A-kinase anchoring protein 1 (AKAP1) and its role in some cardiovascular diseases". Journal of ... Articles with short description, Short description matches Wikidata, A-kinase-anchoring proteins). ...
It should not be confused with cyclic AMP-activated protein kinase (protein kinase A). AMPK is a heterotrimeric protein complex ... "AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of ... 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC that ... liver kinase B1 (LKB1), which works in a complex with STRAD and MO25, Calcium/calmodulin-dependent protein kinase kinase II-( ...
This gene encodes a nuclear protein, which is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. This ... Wee1-like protein kinase has been shown to interact with YWHAB and PIN1. GRCh38: Ensembl release 89: ENSG00000166483 - Ensembl ... WEE1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology v t e (Genes on ... protein catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition ...
Signal transduction MAP kinase kinase MAP kinase kinase kinase MAP kinase kinase kinase kinase MAPK1 (ERK2) MAPK3 (ERK1) MAPK7 ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... MAP Kinase Resource . Table of names for mitogen-activated kinases. MAPK cascade picture Mitogen-Activated+Protein+Kinases at ... Extracellular signal-regulated kinases (ERKs) c-Jun N-terminal kinases (JNKs) p38 mitogen-activated protein kinases (p38s) ...
... (EC, FN3K, fructosamine 3-kinase) is an enzyme with systematic name ATP:(protein)-N6-D- ... Protein-fructosamine+3-kinase at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC 2.7.1) ... This enzyme catalyses the following chemical reaction ATP + [protein]-N6-D-fructosyl-L-lysine ⇌ {\displaystyle \ ... Szwergold BS, Howell S, Beisswenger PJ (September 2001). "Human fructosamine-3-kinase: purification, sequencing, substrate ...
... also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. This ... Universal protein resource accession number P41240 for "Tyrosine-protein kinase CSK" at UniProt. Bräuninger A, Holtrich U, ... and CSK-homologous kinase (CHK)--endogenous negative regulators of Src-family protein kinases". Growth Factors. 23 (3): 233-44 ... "Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell ...
In molecular biology, the kinase binding protein CGI-121 family of proteins includes the kinase binding protein CGI-121 and its ... CGI-121 has been shown to bind to the p53-related protein kinase (PRPK). CGI-121 is part of a conserved protein complex, KEOPS ... p53-related protein kinase)-binding protein". Biochem. Biophys. Res. Commun. 303 (2): 399-405. doi:10.1016/S0006-291X(03)00333- ... This family of proteins also include archaeal homologues. Miyoshi A, Kito K, Aramoto T, Abe Y, Kobayashi N, Ueda N (April 2003 ...
... is a protein that in humans is encoded by the CDC42BPB gene. This gene encodes a member of ... The encoded protein contains a Cdc42/Rac-binding p21 binding domain resembling that of PAK kinase. The kinase domain of this ... "Entrez Gene: CDC42 binding protein kinase beta". Retrieved 2017-05-31. Choi SH, Czifra G, Kedei N, Lewin NE, Lazar J, Pu Y, ... myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta". J. Biol. Chem. 283 (16): 10543-9. doi:10.1074/jbc. ...
Other names in common use include GPBPK, GPBP kinase, STK11, and Goodpasture antigen-binding protein kinase. This enzyme ... protein-serine/threonine kinases). The systematic name of this enzyme class is ATP:[Goodpasture antigen-binding protein] ... In enzymology, a Goodpasture-antigen-binding protein kinase (EC is an enzyme that catalyzes the chemical reaction ATP ... Vieites B, Granero F, Forteza J, Saus J (2000). "Goodpasture antigen-binding protein, the kinase that phosphorylates the ...
... are a family of protein kinases within the AGC (protein kinase A, protein kinase G, protein kinase C) group of kinases. Like ... GRK2 activity can be modulated by its phosphorylation by protein kinase A or protein kinase C, and by post-translational ... In the folded proteins, the kinase domain forms a typical bi-lobe kinase structure with a central ATP-binding active site. The ... In particular, G protein-coupled receptor kinase 2 is known to interact with a diverse repertoire of non-GPCR partner proteins ...
2002). "Epstein-Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine kinase/uracil phosphoribosyltransferase ... Uridine-cytidine kinase-like 1 is an enzyme that in humans is encoded by the UCKL1 gene. GRCh38: Ensembl release 89: ... "Entrez Gene: UCKL1 uridine-cytidine kinase 1-like 1". Beausoleil SA, Villén J, Gerber SA, et al. (2006). "A probability-based ... approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285-92. doi: ...
Bone morphogenetic protein (BMP) cell signaling plays a key role in diverse aspects of cardiac differentiation and ... BMP influences AV node development through Alk3 receptor (Activin receptor-like kinase 3). Abnormalities seen in BMP and Alk3 ...
... the cell grows in size and synthesizes mRNA and protein that are required for DNA synthesis. Once the required proteins and ... Biochemical triggers known as cyclin-dependent kinases (Cdks) switch on cell cycles events at the corrected time and in the ... In these cases where the G1 phase is affected, it is generally because gene regulatory proteins of the E2F family have become ... In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 ...
As mentioned previously, 6 N-myristoylation sites, 2 cAMP phosphorylation sites, and 4 protein kinase C phosphorylation sites ... "Protein BLAST: search protein databases using a protein query". Retrieved 2021-08-01. (CS1 maint: url- ... Stimulating protein 1, CCAAT/enhancer binding protein, GC box elements and HMG box-containing protein 1. Like previously ... PANO1 is a protein which in humans is encoded by the PANO1 gene. PANO1 is an apoptosis inducing protein that is able to ...
Moss SJ, Doherty CA, Huganir RL (July 1992). "Identification of the cAMP-dependent protein kinase and protein kinase C ... Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (January 2000). "Direct protein-protein coupling enables cross-talk ... Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (January 2000). "Direct protein-protein coupling enables cross-talk ... Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene. Gamma-aminobutyric ...
c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein ... A number of tyrosine kinase inhibitors that target c-Src tyrosine kinase (as well as related tyrosine kinases) have been ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ... Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase ...
2002). "A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated with focal adhesion kinase and ... C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene. The protein ... "Entrez Gene: MAPK8IP3 mitogen-activated protein kinase 8 interacting protein 3". Matsuura, Hiroshi; Nishitoh Hideki; Takeda ... a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". ...
2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. ... Some studies have shown that this differentiation is due to many CAD kinase substrates. Referring to the example of skeletal ... The protein caspase DNase is an endonuclease involved in the cell apoptotic process that facilitates the DNA breakup. Cell ... It also depends on the activity of a protein or a common signal. The factor that seems to induce more cell differentiation is ...
"Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC". Mol. Cell. 10 (2): 247-58. ... Nucleolar protein 3 is a protein that in humans is encoded by the NOL3 gene. NOL3 has been shown to interact with SFRS9 and ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/ ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode:2005Natur. ...
After Fas stimulation, Daxx is activated and plays its role of pro-apoptotic protein in activating the c-JUN-N-Terminal Kinase ... Death-associated protein 6 also known as Daxx is a protein that in humans is encoded by the DAXX gene. Daxx, a Death domain- ... This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate ... Daxx does not activate JNK itself but rather the upstream JNK kinase kinase ASK1. Some kind of positive feedback system was ...
Epidermal growth factor receptor kinase substrate 8-like protein 1 is an enzyme that in humans is encoded by the EPS8L1 gene. ... This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the ... The function of this protein is unknown. Several alternatively spliced transcript variants encoding different isoforms exist. ... 2004). "The eps8 Family of Proteins Links Growth Factor Stimulation to Actin Reorganization Generating Functional Redundancy in ...
"A direct interaction between G-protein beta gamma subunits and the Raf-1 protein kinase". J. Biol. Chem. 270 (24): 14251-4. doi ... Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 is a protein that in humans is encoded by the GNG4 gene. GNG4 ... "Entrez Gene: GNG4 guanine nucleotide binding protein (G protein), gamma 4". Yan K, Kalyanaraman V, Gautam N (Mar 1996). " ... "Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and ...
In addition, its high dose (200nM/mouse) combination with H-89, as a protein kinase inhibitor, had additive attenuating effect ...
Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take ... Proteins are made of amino acids arranged in a linear chain joined by peptide bonds. Many proteins are enzymes that catalyze ... In prokaryotes, these proteins are found in the cell's inner membrane. These proteins use the energy from reduced molecules ... Amino acids are made into proteins by being joined in a chain of peptide bonds. Each different protein has a unique sequence of ...
It exists in its own granule after translation, and release of the protein is triggered by Protein Kinase C (PKC). Its C- and N ... It is expressed in 2 forms: a 15kDa precursor protein, the translation product, and a 9kDa cytotoxic protein, which is formed ... Orthologs of this protein are found in most mammal species, such as in cows and pigs, however not in rodents. Granulysin is ... It is part of the saponin-like protein family, and its gene is found on the 2nd chromosome in humans. It is distinguished by ...
To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special ... Karin, M; Delhase, M (2000). "The I kappa B kinase (IKK) and NF-kappa B: Key elements of proinflammatory signalling". Seminars ... Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; ... The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, ...
The activation of the rho kinase pathway leads to the phosphorylation of proteins which inhibit neurite outgrowth. Myelin ... MAG can also act as a signaling molecule as a soluble protein after it has been proteolytically shed. This form of the protein ... MAG is a member of the SIGLEC family of proteins and is a functional ligand of the NOGO-66 receptor, NgR. MAG is believed to be ... MAG is a critical protein in the formation and maintenance of myelin sheaths. MAG is localized on the inner membrane of the ...
Splicing factor, arginine/serine-rich 6 is a protein that in humans is encoded by the SFRS6 gene. The protein encoded by this ... Gui JF, Lane WS, Fu XD (June 1994). "A serine kinase regulates intracellular localization of splicing factors in the cell cycle ... The encoded nuclear protein belongs to the splicing factor SR family and has been shown to bind with and modulate another ... "Entrez Gene: SFRS6 splicing factor, arginine/serine-rich 6". Zahler AM, Lane WS, Stolk JA, Roth MB (May 1992). "SR proteins: a ...
Heat shock 70kDa protein 1B is a chaperone protein, cooperating with other heat shock proteins and chaperone systems to ... Zhu D, Dix DJ, Eddy EM (August 1997). "HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes". ... Expression of heat shock protein 70kDa protein 2 in transformed tumor cells has been implicated in the rapid proliferation, ... Zeke T, Morrice N, Vázquez-Martin C, Cohen PT (January 2005). "Human protein phosphatase 5 dissociates from heat-shock proteins ...
... is a kinase inhibitor, meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from ... decreased protein level, decreased calcium, increased total cholesterol, increased creatinine, and decreased sodium) dry mouth ... Receptor tyrosine kinase inhibitors, Tissue agnostic antineoplastic agents). ...
... at position 375 of VP16 is critical for complex assembly with Oct-1 and HCF and is a target of phosphorylation by casein kinase ... Stynen, B.; Tournu, H.; Tavernier, J.; Van Dijck, P. (11 June 2012). "Diversity in Genetic In Vivo Methods for Protein-Protein ... Vmw65, also known as VP16 or α-TIF (Trans Inducing Factor) is a trans-acting protein that forms a complex with the host ... v t e (Simplexviruses, Viral nonstructural proteins, All stub articles, Virus stubs). ...
... mitogen-activated protein kinase and nuclear factor-κB". Int. J. Mol. Med. 30 (2): 344-50. doi:10.3892/ijmm.2012.1000. PMID ... Phylogenetic relationships of Sparassis inferred from nuclear and mitochondrial ribosomal DNA and a protein-coding gene (rpb2 ...
Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription. Antiviral and ... cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 ... to prevent the activity of RNA-dependent protein kinases; this is the mechanism reovirus adopts using its sigma 3 (σ3) protein ... Production of protein kinase R, for example, can be disrupted in cells infected with JEV. Some viruses escape the anti-viral ...
CDC42, protein tyrosine kinase, phosphoinositide 3-kinase, and Src-family kinases then activate Arp2/3. This causes the ... This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called ... Both rOmpA and rOmpB are members of a family of surface cell antigens (Sca) which are autotransporter proteins; they act as ... "Rickettsial Outer-Membrane Protein B (rOmpB) Mediates Bacterial Invasion through Ku70 in an Actin, c-Cbl, Clathrin and Caveolin ...
Serine/threonine-protein kinase D3). Neault et al. recently identified miR-137 as a senescence effector miRNA induced by ... By suppressing Jarid1b protein level, miR-137 is believed to play a role in modulating the differentiated state of mouse ESCs. ... miR-137 is located on chromosome 1p22 within the non-protein-coding RNA gene AK094607. It is transcribed as a non-coding ... This binding in turn results in an inhibition of translation of the target protein or degradation of the target messenger RNA. ...
"The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase ... Ren Y, Busch RK, Perlaky L, Busch H (May 1998). "The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with ... Ren Y, Busch RK, Perlaky L, Busch H (1998). "The 58-kDa microspherule protein (MSP58), a nucleolar protein, interacts with ... "Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein ...
Diviani D, Soderling J, Scott JD (November 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho- ... Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG". The Journal of ... Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG". The Journal of ... Ras homolog gene family, member B, also known as RHOB, is a protein which in humans is encoded by the RHOB gene. RHOB is a ...
1994). "Activation of p34cdc2 protein kinase by microinjection of human cdc25C into mammalian cells. Requirement for prior ... The encoded protein is a tyrosine phosphatase and belongs to the Cdc25 phosphatase family. It directs dephosphorylation of ... Booher RN, Holman PS, Fattaey A (1997). "Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity ... Gould KL, Moreno S, Tonks NK, Nurse P (Feb 1991). "Complementation of the mitotic activator, p80cdc25, by a human protein- ...
Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ... "A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle". ... "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ... Cao C, Leng Y, Li C, Kufe D (April 2003). "Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the ...
"The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal ... Formin-like protein 1 is a protein that in humans is encoded by the FMNL1 gene. This gene encodes a formin-related protein. ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-1178. Bibcode: ... Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. An alternative splice variant ...
Atypical protein kinase C iota (PKCι) is a serine/threonine kinase that has been implicated in both epithelial polarity and ... Differentiating protein kinase C iota functions through multiple PKCι-partner complexes ... Proteomic screens have identified RIPR-dependent PKCι interacting proteins, amongst which two protein families, MTA and FARP, ... FERM, RhoGEF and pleckstrin domain-containing protein 1 and 2 (FARP1, 2) are Cdc42/Rac1 guanine nucleotide exchange factors ( ...
Marine Derived Hamacanthins as Lead for the Development of Novel PDGFRβ Protein Kinase Inhibitors by Boris Pinchuk ... Interests: design; synthesis and biological evaluation of protein kinase inhibitors. Special Issues, Collections and Topics in ... Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the ... All the compounds were evaluated for their potential inhibitory activity against eight different protein kinases involved in ...
General protein information Go to the top of the page Help Preferred Names. serine-threonine kinase receptor-associated protein ... mRNA and Protein(s) * NM_011499.3 → NP_035629.2 serine-threonine kinase receptor-associated protein ... serine/threonine kinase receptor associated proteinprovided by MGI. Primary source. MGI:MGI:1329037 See related. Ensembl: ... Serine threonine kinase receptor associated protein regulates early follicle development in the mouse ovary. Sharum IB, et al. ...
... Alistair RR Forrest1, Timothy Ravasi2, Darrin Taylor, ... This approach identified 561 candidate protein kinases and 162 candidate protein phosphatases. This cohort was then analysed ... This approach allowed us to 1) distinguish between true members of the protein kinase and phosphatase families and enzymes of ... In this paper we have undertaken a computational approach to identify and classify all the protein kinases and phosphatases ...
NEW YORK (GenomeWeb News) - Procognia said today that GlaxoSmithKline will use its protein arrays to profile kinase kits in ... Under the agreement, GSK will use Procognias protein array technology with its own kinase inhibitors in profiling studies to ... GSK to Test-Run Procognias Protein Arrays for Kinase-Screening Studies Mar 23, 2007 ... Procognia also said its protein arrays are used for biomarker discovery, protein interaction, and in identifying substrates. ...
Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied ... Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3- ... Role of AMP-activated protein kinase in mechanism of metformin action. Gaochao Zhou,1 Robert Myers,1 Ying Li,1 Yuli Chen,1 ... AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol 1999. 277:E1-E10. View ...
Mitogen-activated protein kinase 14 (human). Find diseases associated with this biological target and compounds tested against ...
S.P. Davies et al., Specificity and mechanism of action of some commonly used protein kinase inhibitors, Biochemical Journal ... Cited in 191 papers) In signal transduction research, protein kinase inhibitors help scientists tease out the vagaries of ... S.P. Davies et al., "Specificity and mechanism of action of some commonly used protein kinase inhibitors," Biochemical Journal ... Researchers Are Getting Specific About Protein Kinase Inhibitors. Data derived from the Science Watch/Hot Papers database and ...
It is a multifunctional Ca2+/calmodulin-dependent protein kinase capable of phosphorylating protein substrates, such as AMPA ... Importance of spatial localization to kinase action. Protein kinases, including CaMKII, can be pre-positioned near their ... polyadenylation element binding protein-dependent protein synthesis is regulated by calcium/calmodulin-dependent protein kinase ... Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I. Nature 359: 417- ...
Protein kinase inhibitors market size, demand & analysis, by type (serine/ threonine, tyrosine, histidine), by therapy ( ... the protein kinase inhibitors market share is segmented into Serine/Threonine kinases, Tyrosine Kinases, Histidine Kinases, and ... Protein kinases are enzymes that have the potential to modify or alter proteins by attaching phosphate groups to threonine, ... Protein kinases then send signals from the cell membrane into the interior of the cell, and this activation of the signaling ...
Timeline for Protein Tagatose-6-phosphate kinase LacC from c.72.1.1: Ribokinase-like: *Protein Tagatose-6-phosphate kinase LacC ... Lineage for Protein: Tagatose-6-phosphate kinase LacC. *Root: SCOPe 2.08 *. Class c: Alpha and beta proteins (a/b) [51349] (148 ... Protein Tagatose-6-phosphate kinase LacC from c.72.1.1: Ribokinase-like appears in SCOPe 2.07. ... More info for Protein Tagatose-6-phosphate kinase LacC from c.72.1.1: Ribokinase-like. ...
Structural Mechanisms in Protein Kinase Regulation. Add to your list(s) Download to your calendar using vCal ...
May be used to phosphorylate target proteins or for in vitro enzymological studies of neural and hormonal signal transduction ... 40kDa protein purified from a recombinant E. coli strain expressing the catalytic subunit of bovine PKA ... May be used to phosphorylate target proteins or for in vitro enzymological studies of neural and hormonal signal transduction ... Intracellular targets include ion channels, transcriptional activator proteins, and regulatory enzymes of glycogen metabolism ...
The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 ... kinase family of serine/threonine kinases. The human ERK3 protein is made of 721 amino acids and contains a typical kinase ... Schematic representation of the ERK3 protein structure. Kinase, catalytic kinase domain; C34 conserved region in ERK3 and ERK4 ... The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain ...
Octahedral ruthenium complexes as protein kinase inhibitors A new strategy for the design of selective protein kinase ... A new strategy for the design of selective protein kinase inhibitors has been initiated with chemically inert metallo- ... this thesis had the goal to develop octahedral ruthenium complexes as protein kinase inhibitors.. ... alkaloid structure was replaced with simple metal complex to match the shape of the ATP-binding site of protein kinases (Figure ...
protein coding gene. Chr4:132965290-132980240 (+). 129S1/SvImJ MGP_129S1SvImJ_G0028889. protein coding gene. Chr4:135475570- ... protein coding gene. Chr4:144001082-144013134 (+). DBA/2J MGP_DBA2J_G0028700. protein coding gene. Chr4:130230935-130242988 (+) ... protein coding gene. Chr4:133492776-133504830 (+). BALB/cJ MGP_BALBcJ_G0028871. protein coding gene. Chr4:130431492-130443541 ... protein coding gene. Chr4:133744389-133756443 (+). C57BL/6NJ MGP_C57BL6NJ_G0029313. protein coding gene. Chr4:140346661- ...
... of kinetochore protein kinases KKT10/KKT19 was used to show that XL-BioID provides a spatially focussed view of protein kinase ... Protein kinase signalling at the Leishmania kinetochore captured by XL-BioID. View ORCID ProfileVincent Geoghegan, View ORCID ... consisting of proximity biotinylation followed by protein cross-linking (XL-BioID). This was applied to protein kinases of the ... Protein kinase signalling at the Leishmania kinetochore captured by XL-BioID Message Subject (Your Name) has forwarded a page ...
Proteins and Peptides. By product type. Proteomics tools. Agonists, activators, antagonists and inhibitors. Cell lines and ... Amyloid Precursor Protein+Tau+VEGF Receptor 1+Alpha-synuclein+Natriuretic Peptide Receptor A/GC-A+Ni (1). ...
View and buy high purity products active at Death-Associated Protein Kinase (DAPK) from Tocris Bioscience. ... Death-Associated Protein Kinase. The death-associated protein kinase (DAPK) family contains three closely-related members: DAPK ... Death-Associated Protein Kinase Gene Data. Gene Species Gene Symbol Gene Accession No. Protein Accession No. ... Literature for Death-Associated Protein Kinase. Tocris offers the following scientific literature for Death-Associated Protein ...
Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase ... Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal ... Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube ... Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube ...
... the enzyme Fructosamine-3-kinase is responsible for catalyzing phosphorylation of fructosamines constructed by glycation. The ... About Fructosamine 3 Kinase \ FN3K:. Fructosamine 3-kinase (FN3K) is an enzyme that catalyzes the phosphorylation of ... FN3K phosphorylates protein-bound or low-molecular-mass fructosmaines on the third carbon. Protein-bound fructoselysine becomes ... Fructosamine 3 Kinase Interaction. There is said to be an association between Chronic Obstructive Pulmonary Disease (COPD) and ...
... subunits with A-kinase anchoring proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned ... Engineering A-kinase anchoring protein (AKAP)-selective regulatory subunits of protein kinase A (PKA) through structure-based ... Keywords: AKAP; Cell Biology; Compartmentalization; Peptide Arrays; Phage Display; Protein Kinase A (PKA); Structure-based ... subunits with A-kinase anchoring proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned ...
Butyrate-mediated Signal Transduction in Colonocytes: Role of cAMP-dependent Protein Kinase. ...
The present study explored the potential roles of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 (ARRB2) that ... Genetic association between G protein-coupled receptor kinase 6/β-arrestin 2 and dopamine supersensitivity psychosis in ... Tang W, Cai J, Yi Z, Zhang Y, Lu W, Zhang C. Association study of common variants within the G protein-coupled receptor kinase ... G protein-coupled receptor kinase/beta-arrestin systems and drugs of abuse: psychostimulant and opiate studies in knockout mice ...
Crystal structure of death-associated protein kinase 1 in complex with the dietary compound resveratrol ... Death-associated protein kinase 1 (DAPK1) is a large multidomain protein with an N-terminal serine/threonine protein kinase ... To date, the ATPase activities of mitogen-activated protein/ERK kinase kinase 2 (MEKK2), MEK1, protein kinase C (PKC), dual- ... the protein kinase C (PKC) signaling pathway and the phospho-inositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway ...
... Published: 08th May 2020 ... To arise in the very same client inhabitants and upon application of receptor tyrosine kinase inhibi. ...
The human Cdk-activating protein kinase (Cak1) is itself a Cdc2-related cyclin-dependent protein kinase that associates with ... The activation of cyclin-dependent protein kinases (Cdks) is dependent upon site-specific phosphorylation and dephosphorylation ... Immunoprecipitation of metabolically labeled human osteosarcoma cells revealed a number of Cak1-associated proteins, including ... enabling studies of kinase autophosphorylation and comparative substrate utilization. Immunoaffinity-purified Cak1 ...
... from Soybean Calcium-dependent Protein Kinase-alpha (CDPK) ... Calcium-dependent protein kinase SK5. A. 87. Glycine max. ... Ca(2+)-dependent protein kinases (CDPKs) are vital Ca(2+)-signaling proteins in plants and protists which have both a kinase ... Ca(2+)-dependent protein kinases (CDPKs) are vital Ca(2+)-signaling proteins in plants and protists which have both a kinase ... A calcium-dependent protein kinase with a regulatory domain similar to calmodulin. Harper, J.F., Sussman, M.R.,& ...
Serine/threonine-protein kinase 24. Details. Name. Serine/threonine-protein kinase 24. Kind. protein. Organism. Humans. Protein ... Serine/threonine-protein kinase 24. Q9Y6E0. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. ...
Protein_regulators_of_kinase_C.pdf Download (7MB) Abstract. Protein Kinase C (PKC) is a family of serine/threonine kinases. The ... PKCI (protein kinase C inhibitor), was originally purified from bovine brain. In this study a maize gene similar to bovine PKCI ... Protein regulators of kinase C. Doctoral thesis (Ph.D), UCL (University College London). ... Other proteins share this cysteine-rich region, for example c- raf-1, n-chimaerin, DAG kinase and phospholipase A2(PLA2). ...
  • Atypical protein kinase C iota (PKCι) is a serine/threonine kinase that has been implicated in both epithelial polarity and oncogenic transformation. (
  • Orthologous to human STRAP (serine/threonine kinase receptor associated protein). (
  • Serine threonine kinase receptor associated protein regulates early follicle development in the mouse ovary. (
  • Serine threonine receptor-associated protein (STRAP) plays a role in the maintenance of mesenchymal morphology. (
  • Serine-threonine Kinase Receptor-Associated Protein is a Critical Mediator of APC Mutation-Induced Intestinal Tumorigenesis Through a Feed-Forward Mechanism. (
  • Protein kinases are enzymes that have the potential to modify or alter proteins by attaching phosphate groups to threonine, tyrosine, and serine residues. (
  • On the basis of type, the protein kinase inhibitors market share is segmented into Serine/Threonine kinases, Tyrosine Kinases, Histidine Kinases, and others. (
  • Extracellular signal-regulated kinase 3 (ERK3) is an atypical member of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. (
  • ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. (
  • The death-associated protein kinase (DAPK) family contains three closely-related members: DAPK (also known as DAPK1), DAPK-related protein 1 (DRP-1) and ZIP kinase (ZIPK), all of which are serine/threonine kinases involved in apoptotic and autophagic cell death. (
  • Death-associated protein kinase 1 (DAPK1) is a large multidomain protein with an N-terminal serine/threonine protein kinase domain. (
  • Death-associated protein kinase 1 (DAPK1) is a Ca 2+ /calmodulin-regulated serine/threonine protein kinase (CaMK) composed of an N-terminal catalytic kinase domain, a Ca 2+ /calmodulin-binding domain, ankyrin repeats, an Roc/COR domain and a death domain. (
  • Protein Kinase C (PKC) is a family of serine/threonine kinases. (
  • Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-dependent serine/threonine kinase that is thought to mediate apoptosis. (
  • Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that are protein kinase inhibitors (PKI). (
  • Under the agreement, GSK will use Procognia's protein array technology with its own kinase inhibitors in profiling studies to assess whether it can integrate these arrays into its screening process. (
  • Specificity and mechanism of action of some commonly used protein kinase inhibitors," Biochemical Journal, 351:95-105, Oct. 1, 2000. (
  • In signal transduction research, protein kinase inhibitors help scientists tease out the vagaries of complex signaling pathways, but anecdotal evidence suggests that they are flawed tools at best, lacking the specificity necessary to draw conclusions from their use. (
  • The Global Protein Kinase Inhibitors Market size is estimated to reach USD XX billion, delivering a CAGR of XX% through 2027. (
  • Protein kinase inhibitors are witnessing high demand for therapies due to the high efficacy rate in the treatment for a cardiac disorder, cancer, diabetes, and others. (
  • Since protein kinase inhibitors are helpful in the treatment of several diseases, it is witnessing heavy demand in targets for drug discovery and treatment therapies. (
  • In the modern medical research landscape, protein kinase inhibitors are one of the most important categories of targets in drug discovery and oncology on account of their pivotal roles in regulating cellular growth and survival. (
  • Nearly 14 nibs (small molecule Protein kinase Inhibitors) have been approved by the Food and Drug Administration for the treatment of various types of cancers, and several candidates are in different stages of clinical trials. (
  • Substantial funding from private and government institutes for the development of target therapies will boost the protein kinase inhibitors market growth. (
  • Several industry players are offering kinase inhibitors for disease treatment. (
  • For instance, BioVision, a San-Francisco-based life science company, offers some 700 protein kinase inhibitors specific for a certain cellular pathway as part of its product portfolio. (
  • On the basis of therapy, the protein kinase inhibitors market is classified into Combination Therapy And Monotherapy. (
  • The combination therapy is estimated to hold a major chunk of the protein kinase inhibitors market share as it offers a wide therapeutic range due to its safety and efficacy. (
  • Based on drug class, the protein kinase inhibitors market is classified as Indolocarbazole, Phorbol Esters, Nonsteroidal Anti-Oestrogen, Macrocyclic Lactones, and Others. (
  • Asia Pacific is estimated to exhibit notable CAGR in the protein kinase inhibitors market due to a rise in medical research activity and a high number of new entrants offered by the region. (
  • Kinnate Biopharma announced on 26th August 2020 that it had raised USD 98 million in a recent funding round, and the company will be utilizing it to push its kinase inhibitors pipeline to develop targeted therapies for cancer treatment. (
  • A new strategy for the design of selective protein kinase inhibitors has been initiated with chemically inert metallo-pyridocarbazoles scaffold by the group of Prof. Meggers since 2004. (
  • Whereas previous work was focused mainly on half-sandwich complexes, this thesis had the goal to develop octahedral ruthenium complexes as protein kinase inhibitors. (
  • Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases? (
  • BioVision proudly offers an array of STAT inhibitors either directly acting on STAT proteins or other proteins playing critical roles in the STAT signaling pathway. (
  • The toxicity data of protein kinase inhibitors in humans is also well established [5]. (
  • 4. Prior therapy with BRAF and MEK protein kinase inhibitors. (
  • It is indicated for adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) who were previously treated with ≥2 tyrosine kinase inhibitors (TKIs). (
  • Comparing a variety of kinases, only rhodopsin kinase and casein kinase II exhibited significant phosphorylation of the acidic peptides. (
  • For example, a purified enzyme is reacted with a substrate protein or mixture of proteins or peptides. (
  • STRAP Acts as a Scaffolding Protein in Controlling the TLR2/4 Signaling Pathway. (
  • ERK3 is a highly unstable protein, with a half-life of less than one hour, that is constitutively degraded by the ubiquitin-proteasome pathway. (
  • Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. (
  • Like many proteins, DAPK is degraded by the ubiquitin- proteasome pathway. (
  • This led me to define and name the AMP-activated protein kinase (AMPK) signalling pathway, on which I am still working 46 years later. (
  • The authors of this paper by Yusuke Murakami, Hidetaka Matsumoto, Miin Roh, Jun Suzuki, Toshio Hisatomi, Yasuhiro Ikeda , Joan W. Miller , and Demetrios G. Vavvas have further defined the process and identified the receptor interacting protein kinase (RIP) pathway as a possible target for intervention in patients with retinitis pigmentosa (RP). (
  • Bioinformatics analysis indicated that mitogen-activated protein kinase (MAPK) signaling was the major pathway in both levels of noise exposure. (
  • The Protein kinase C (PKC) -associated sign pathway performs essential roles in regulation of cell development, differentiation and apoptosis. (
  • mTOR is phosphorylated at Ser2448 via the PI3 kinase/Akt signaling pathway and autophosphorylated at Ser2481 (7,8). (
  • Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis. (
  • In this paper we have undertaken a computational approach to identify and classify all the protein kinases and phosphatases present in the mouse gene complement. (
  • Protein kinases then send signals from the cell membrane into the interior of the cell, and this activation of the signaling pathways results in the reprogramming of gene expression. (
  • Review on MAPK6, with data on DNA, on the protein encoded, and where the gene is implicated. (
  • Tyrosine kinases (for example: Janus Kinase/JAK) associated to the growth factor/cytokine receptors phosphorylate STAT proteins which results in their dimerization and transport into the nucleus followed by binding to target gene regulatory elements thus controlling gene expression. (
  • Gene expression profiling of the Deltahog1 deletion mutant indicated an involvement of the mitogen activated protein (MAP) kinase Hog1p. (
  • Thus, our results suggest that the kinase domain deleted by gene targeting plays a suppressive role for the development of renal fibrosis through inhibition of the tubular epithelial-to-mesenchymal transition in a mouse model of COU. (
  • This gene encodes a member of the adenylate kinase family, which is involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. (
  • The FGFR4 gene provides instructions for making a protein called fibroblast growth factor receptor 4. (
  • A variation (polymorphism) in the FGFR4 gene that causes a switch in amino acids (the building blocks of proteins) is associated with several types of cancer, such as those that occur in the breast, colon, head and neck, and prostate. (
  • Through these experiments, the scientists determined that B. henselae can stimulate angiogenesis in human endothelial cells only if it possesses a functional copy of the gene that "codes for," or guides the synthesis of, the BafA protein. (
  • The human protein Kinase C gamma gene (PRKCG) as a susceptibility locus for behavioral disinhibition. (
  • In the regional landscape, North America accounts for the largest share in the global protein kinase inhibitor market due to advanced drug research as well as development activities in the region. (
  • The major players contributing to the protein kinase inhibitor market share are Boehringer Ingelheim, Eli Lilly. (
  • A specific inhibitor of kinetochore protein kinases KKT10/KKT19 was used to show that XL-BioID provides a spatially focussed view of protein kinase inhibition, identifying 16 inhibitor-responsive proximal phosphosites, including 3 on KKT2, demonstrating the potential of this approach for discovery of in vivo kinase signalling pathways. (
  • PKCI (protein kinase C inhibitor), was originally purified from bovine brain. (
  • Laufer, SA From off-to on-target: New BRAF-inhibitor-template-derived compounds selectively targeting mitogen activated protein kinase kinase 4 (MKK4). (
  • The model was validated using an independent data set of 645 patients treated with tyrosine kinase inhibitor (TKI) therapy. (
  • The compound is an inhibitor of mammalian protein kinase and has been applied topically for the treatment of skin metastasis showing good local tolerability [5]. (
  • When sufficient nutrients are available, mTOR responds to a phosphatidic acid-mediated signal to transmit a positive signal to p70 S6 kinase and participate in the inactivation of the eIF4E inhibitor, 4E-BP1 (6). (
  • Asciminib is a tyrosine kinase inhibitor that binds to ABL myristoyl pockets, thereby inhibiting ABL1 kinase activity of the BCR-ABL1 fusion protein. (
  • Pegcetacoplan is a complement inhibitor that acts by binding to complement protein C3 and its activation fragment C3b, thereby regulating C3 cleavage and generation of downstream effectors of complement activation. (
  • Cohen, Royal Society research professor and director of the Medical Research Council's protein phosphorylation unit, University. (
  • This review will discuss the role of kinase localization in optimizing fidelity of substrate phosphorylation. (
  • First, localization of kinase near some of its substrates achieves a concentration of the kinase that speeds onset of response to stimulus and increases the rate of phosphorylation. (
  • Nuclear targeting is subject to inhibitory control by phosphorylation at either of two sites, one catalyzed by other kinases and the other by autophosphorylation. (
  • Fructosamine 3-kinase (FN3K) is an enzyme that catalyzes the phosphorylation of fructosamines. (
  • The activation of cyclin-dependent protein kinases (Cdks) is dependent upon site-specific phosphorylation and dephosphorylation reactions, as well as positive and negative regulatory subunits. (
  • A casual decision made one evening in 1976, in a bar near the Biochemistry Department at the University of Dundee, led me to start my personal research journey by following up a paper that suggested that acetyl-CoA carboxylase (ACC) (believed to be a key regulatory enzyme of fatty acid synthesis) was inactivated by phosphorylation by what appeared to be a novel, cyclic AMP-independent protein kinase. (
  • Since the exact sites of receptor phosphorylation by beta-ARK are poorly defined, the identification of substrate amino acids that are critical to phosphorylation by the kinase are also unknown. (
  • Removal of the negatively charged amino acids surrounding a cluster of serines in this alpha 2-peptide resulted in a complete loss of phosphorylation by the kinase. (
  • M2.2 protein interferes with MAVS and inhibits IRF7 phosphorylation. (
  • Downstream of SHP1 and SYK-dependent counterregulation of MyD88 tyrosine phosphorylation , we have demonstrated that the scaffolding function of receptor interacting protein kinase 1 (RIPK1) and tumor growth factor -ß activated kinase 1 (TAK1)- mediating signaling were required to spur inflammatory disease . (
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a pleiotropic protein kinase that plays critical roles in cellular processes fundamental to cancer. (
  • The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. (
  • This approach allowed us to 1) distinguish between true members of the protein kinase and phosphatase families and enzymes of related biochemistry 2) determine the structure of the families and 3) suggest functions for previously uncharacterized members. (
  • Liver function enzymes, aspartate aminotransferase, and alanine aminotransferase activities including total cholesterol, total protein, albumin, and globulin were not changed by BV supplementation. (
  • A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. (
  • The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival. (
  • DAPK-mutant mice, generated by deletion of 74 amino acids from the catalytic kinase domain, were used to investigate the role of the DAPK kinase domain in renal fibrosis following COU. (
  • The cAMP-dependent protein kinase (PKA) holoenzyme is composed of two regulatory and two catalytic subunits, designated PKA R and PKA C, respectively. (
  • Involvement of protein kinase C in fluoride-induced apoptosis in different types of lung cells. (
  • We have shown that the kinase domain of DAPK is crucial for the induction of renal tubular cell apoptosis in chronic obstructive uropathy (COU) created by unilateral ureteral ligation. (
  • Previous studies on Bartonella henselae (B. henselae for short), the bacterium responsible for cat-scratch disease, have shown that it can directly "inject" proteins that inhibit programmed cell death (apoptosis) into the endothelial cells. (
  • Elucidating protein kinase signaling pathways is an important but challenging problem in cell biology. (
  • It is a calmodulin (CaM)-regulated kinase that has been implicated in a variety of diverse signaling pathways involved in cell death, immune and inflammatory responses. (
  • Further research into the cross-talk between these kinases may yield greater understanding of the complex signaling pathways involved in cell death and survival. (
  • The aim of this study was to explore the impact of Ras homolog C/Rho-associated coiled-protein kinase (Rho/ROCK) signaling pathways intervention on biological characteristics of the human multiple myeloma cell lines RPMI-8226 and U266 cells, and to investigate the expression of RhoC, ROCK1, and ROCK2 in RPMI-8226 and U266 cells. (
  • Explore pathways + proteins related to this product. (
  • This generalisable approach provides unprecedented temporal control over the dose of endogenous proteins in mouse models, with implications for studying essential biological pathways and modelling drug activity in mammalian tissues. (
  • Early steps in this transition are complex, with at least 2 signaling pathways identified: 1 stops yeast growth and another, with a heat shock protein 70-type profile, initiates the assembly of proteins necessary for mycelial growth. (
  • Calcium-dependent signaling pathways and heat shock protein expression regulate dimorphism in Paracoccidioides brasiliensis and have broad implications for other pathogens. (
  • Procognia also said its protein arrays are used for biomarker discovery, protein interaction, and in identifying substrates. (
  • Proper function of the kinase requires that it access and selectively phosphorylate numerous substrates in diverse intracellular sites. (
  • IMSEAR at SEARO: On the structural features of the substrates of protein kinase. (
  • Abcam: antibodies, proteins, kits. (
  • This approach identified 561 candidate protein kinases and 162 candidate protein phosphatases. (
  • The STAT proteins can be dephosphorylated by nuclear phosphatases, which lead to their inactivation and they are transported out of the nucleus into the cytosol awaiting the next round of activation signal. (
  • Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase by the PTP2 and PTP3 protein tyrosine phosphatases. (
  • Many growth factors, cytokines, hormones like insulin and their receptors relay intracellular signals through STAT proteins. (
  • The beta-adrenergic receptor kinase (beta-ARK) phosphorylates G protein coupled receptors in an agonist-dependent manner. (
  • This protein is part of a family of fibroblast growth factor receptors that share similar structures and functions. (
  • Its activity is directed by intracellular signals mediated by various types of receptors such as G protein-coupled receptors. (
  • A further chapter discusses how surface membrane G-protein receptors in C. albicans and other fungi transmit external stimuli through 2 major protein kinase cascades. (
  • CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. (
  • Such studies concluded that removing 3DG, by inhibition of Fructosamine 3-kinase, was a feasible option to treat diabetes and similar diseases. (
  • The present study explored the potential roles of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 (ARRB2) that are involved in the trafficking of DRD2 in patients with DSP. (
  • A purified adenovirus 289-amino-acid E1A protein activates RNA polymerase III transcription in vitro and alters TFIIIC. (
  • Unlike rapamycin, which also binds to FK506-binding protein-12, FKBP12 with or without bound FK506 has no effect on rat brain PKC activity in vitro. (
  • Atypical mitogen-activated protein kinases: structure, regulation and functions. (
  • STAT proteins also known as Signal Transducer and Activator of Transcription are transcription factors involved in a huge repertoire of biological signal transduction cascades leading to embryonic development, programmed cell death, organogenesis, innate immunity, adaptive immunity and cell growth regulation in organisms ranging from insects to man. (
  • Down-regulation of adenylate kinase 5 in temporal lobe epilepsy patients and rat model. (
  • The Rho family of GTP-binding proteins has been implicated in the regulation of various cellular functions including actin cytoskeleton-dependent morphological change. (
  • The guanine nucleotide exchange factor (GEF) Dbl targets Rho family proteins thereby stimulating their GDP/GTP exchange, and thus is believed to be involved in receptor-mediated regulation of the proteins. (
  • CONCLUSIONS: In C. albicans, the MAP kinase Hog1p is part of the network regulating the response of the organism to iron availability. (
  • Our results showed that all dosages induced no significant alterations in growth parameters and the seric levels of total protein, albumin, globulin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides and activities of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase and lactate dehydrogenase, when compared to the control group. (
  • The human ERK3 protein is made of 721 amino acids and contains a typical kinase domain located at the N-terminal extremity. (
  • ERK3 display 73% amino acid identity with ERK4 in the kinase domain. (
  • The mammalian target of rapamycin (mTOR, FRAP, RAFT) is a Ser/Thr protein kinase (1-3) that functions as an ATP and amino acid sensor to balance nutrient availability and cell growth (4,5). (
  • CaMKII isoforms are highly homologous, but the variable domain can contain peptide segments ("inserts"), e.g., by alternative splicing, that promote distinct intracellular targeting that can involve anchoring proteins. (
  • Kinase isoforms with distinct targeting sequences can coassemble into the same holoenzyme, and thus localization and translocation are dependent on the isoform composition. (
  • The 14-3-3 family consists of highly conserved protein isoforms, with wide range of putative functions. (
  • Differentiation-Associated Expression of Conventional Protein Kinase C Isoforms in Primary Cultures of Bone Marrow Cells Induced by M-CSF and G-CSF. (
  • This activity is known as glycation, and it affects low-molecular-mass compounds and proteins. (
  • Filamin A (FLNA) is a ubiquitously expressed actin-crosslinking protein that also serves as an intracellular signalling scaffold. (
  • FN3K phosphorylates protein-bound or low-molecular-mass fructosmaines on the third carbon. (
  • We further identified SYK as a critical kinase that phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis in Ptpn6spin mice . (
  • SCOPe: Structural Classification of Proteins - extended. (
  • In general, we advise purchasing the recombinant protein with BSA for use in cell or tissue culture, or as an ELISA standard. (
  • Recent research has suggested that these three kinases interact to form complexes which transmit cell death signals in response to stresses such as detachment from the extracellular membrane , and stimuli including TNF-α, IFN-γ and TGF-β. (
  • Through a large-scale immunopurification of CDK7 complexes and protein microsequencing, a cDNA is isolated that encodes p35 and it is shown that it is the human homologue of Mat1 that is involved in the assembly of CAK, a characteristic feature shared among RING finger proteins. (
  • It is shown that cyclin H and Cdk7 are present and during meiosis, form active complexes in testicular cells and are strong candidates for the activating kinase for cyclin A1-associated kinase. (
  • IFN signaling: 3C protease inhibits activation of antiviral protein complexes. (
  • Rapamycin inhibits protein kinase C activity and stimulates Na+ transport in A6 cells. (
  • For example, the DAPK death domain has been shown to interact with ERK and TSC2 proteins, thus placing it within growth factor signaling cascades. (
  • and the carboxyl terminus of Hsc70-interacting protein (CHIP), which interacts with DAPK via Hsp90. (
  • The closely related kinases DRAK1 and DRAK2 share approximately 50% sequence homology with the DAPK kinase domain, but also lack a calmodulin-regulatory region. (
  • Furthermore, deletion of the kinase domain from DAPK significantly increased the appearance of alpha-SMA-positive myofibroblasts in the renal interstitium during COU. (
  • PKA is retained within distinct subcellular environments by the association of its regulatory type II (RII) subunits with A-kinase anchoring proteins (AKAPs). (
  • Association of the proto-oncogene product dbl with G protein betagamma subunits. (
  • A time lapse experiment of Saccharomyces cerevisiae expressing GFP tagged Cdc15, a protein kinase involves in cytokinesis. (
  • To address this problem an in vivo proximity capturing workflow was developed, consisting of proximity biotinylation followed by protein cross-linking (XL-BioID). (
  • Here we develop CRISPR-engineered mouse lines that enable rapid and highly specific degradation of tagged endogenous proteins in vivo . (
  • Protein kinases (PK) are validated targets for drug discovery, particularly in cancer. (
  • In addition, kinase activation and/or autophosphorylation that expose interaction sites normally occluded by its autoinhibitory domain lead to stimulus-dependent translocation to other targets. (
  • cDNA cloning, expression analysis, chromosome localization and characterization of the recombinant protein. (
  • mitogen-activated protein kinase kinase. (
  • Involvement of the mitogen activated protein kinase Hog1p in the response of Candida albicans to iron availability. (
  • Noise exposure immediately activates cochlear mitogen-activated protein kinase signaling. (
  • Calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous enzyme, present in essentially every tissue but most concentrated in brain. (
  • Ca(2+)-dependent protein kinases (CDPKs) are vital Ca(2+)-signaling proteins in plants and protists which have both a kinase domain and a self-contained calcium regulatory calmodulin-like domain (CLD). (
  • The Maidenhead, UK-based company said it hopes to "have a functional human protein array containing the entire human kinome" in the second quarter of this year. (
  • Most aspects of normal cellular function in the human body are regulated by protein kinases. (
  • Dysfunctional kinase activity in the human body often becomes the root cause of a chronic disease like cancer, as kinase are wholly responsible for regulating many aspects that control migration, cell proliferation, and cell death. (
  • Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor. (
  • Mouse polyclonal antibody raised against a full-length human ABL2 protein. (
  • We are a global provider of human and animal biospecimens: including frozen & FFPE tissue, DNA, RNA, total proteins, blood products and primary cells. (
  • Identification of two active functional domains of human adenylate kinase 5. (
  • They also observed that exposing human endothelial cells to the isolated BafA protein caused the cells to multiply. (
  • By combining ligand titrations with genetic crosses to generate animals with different allelic combinations, we show that degradation kinetics depend upon the dose of the tagged protein, ligand, and the E3 ligase substrate receptor TIR1. (
  • Auxin-inducible degrons are a chemical genetic tool for targeted protein degradation and are widely used to study protein function in cultured mammalian cells. (
  • The alpha granules contain hemostatic proteins such as fibrinogen, vWf, and growth factors (eg, platelet-derived growth factor and transforming growth factors). (
  • The compound interacts with its FK506-binding protein-12 (FKBP12). (
  • This member is related to the UMP/CMP kinase of several species. (
  • The cyclin C/Cdk8 kinase. (
  • Observations and the sequence similarity to the kinase/cyclin pair Srb10/Srb11 in S. cerevisiae suggest that cyclin C and Cdk8 control RNA polymerase II function. (
  • We propose that this structure-directed evolution strategy might be generally applicable for the investigation of other protein interaction surfaces. (
  • The interaction of malaria parasites with erythrocyte menbrane [sic] (Ca2+ + Mg2+ATPase and protein kinase / by Somboon Littricharoenphara. (
  • Dr. O'Shea is being recognized for his work with the signaling protein JAK3 (Janus Kinase 3). (
  • Nanosecond pulsed electric fields activate AMP-activated protein kinase: implications for calcium-mediated activation of cellular signaling [med. (
  • Tocris offers the following scientific literature for Death-Associated Protein Kinase to showcase our products. (
  • The kinase domain of death-associated protein kinase is inhibitory for tubulointerstitial fibrosis in chronic obstructive nephropathy. (
  • The nature of protein kinase c activation by physically defined phospholipid vesicle and diacylgly-cerols. (
  • Activation of transcription factor IIIC by adenovirus E1A protein. (
  • Platelet activation allows binding of these proteins, which bridges adjacent platelets. (
  • NP and M2 protein interfere with PKR activation. (
  • Activation of Rho proteins through release of bound GDP and subsequent binding of GTP, is catalysed by guanine nucleotide exchange factors (GEFs) in the Dbl family. (
  • It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (
  • The small intestines allows properly digested fats, proteins and starches to pass through the cells in order to be used by the body while providing a barrier to keep out foreign substances, large undigested molecules and bacterial products. (
  • The indication is that the oligomerisation status of PKCι contributes to its multifunctionality, which is modulated by coupling with distinct partner proteins. (
  • ERK4 and ERK3 define a distinct subfamily of MAP kinases. (
  • The article is published in conjunction with the Sir Philip Randle Lecture of the Biochemical Society, which I gave in September 2022 at the European Workshop on AMPK and AMPK-related kinases in Clydebank, Scotland. (