Cyclic GMP-Dependent Protein Kinase Type I: A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Cyclic AMP-Dependent Protein Kinase Type II: A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.Cyclic GMP-Dependent Protein Kinase Type II: A cyclic GMP-dependent protein kinase subtype that is expressed predominantly in INTESTINES, BRAIN, and KIDNEY. The protein is myristoylated on its N-terminus which may play a role its membrane localization.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Cyclic AMP-Dependent Protein Kinase Type I: A cyclic AMP-dependent protein kinase subtype primarily found in the CYTOPLASM. They are tetrameric proteins that contain two catalytic subunits and two type I-specific regulatory subunits.Calcium-Calmodulin-Dependent Protein Kinase Type 4: A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Calcium-Calmodulin-Dependent Protein Kinase Type 2: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.Calcium-Calmodulin-Dependent Protein Kinases: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Calcium-Calmodulin-Dependent Protein Kinase Type 1: A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.Benzylamines: Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.Cyclic AMP-Dependent Protein Kinase RIalpha Subunit: A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Kinetics: The rate dynamics in chemical or physical systems.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Dibutyryl Cyclic GMP: N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Cell Line: Established cell cultures that have the potential to propagate indefinitely.Paramecium tetraurelia: A species of ciliate protozoa. It is used in biomedical research.MAP Kinase Signaling System: An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Nucleotides, CycliceIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Protein Kinase C-alpha: A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.Cyclic AMP-Dependent Protein Kinase Catalytic Subunits: Specific enzyme subunits that form the active sites of the type I and type II cyclic-AMP protein kinases. Each molecule of enzyme contains two catalytic subunits.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.AMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.PhosphoproteinsSerine: 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.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Protamine Kinase: An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.src-Family Kinases: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.Protein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.PurinonesProtein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.1-Phosphatidylinositol 4-Kinase: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Time Factors: Elements of limited time intervals, contributing to particular results or situations.G-Protein-Coupled Receptor Kinase 4: A G-protein-coupled receptor kinase subtype that is primarily expressed in the TESTES and BRAIN. Variants of this subtype exist due to multiple alternative splicing of its mRNA.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.Phosphatidylserines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.Sulfonamides: A group of compounds that contain the structure SO2NH2.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.MAP Kinase Kinase Kinases: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.RNA, Double-Stranded: RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Interferon Type I: Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).p21-Activated Kinases: A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)MAP Kinase Kinase 1: An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESNitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Sirtuins: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Phorbol 12,13-Dibutyrate: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Cyclic AMP Response Element-Binding Protein: A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Sirtuin 1: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.MAP Kinase Kinase 4: A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Casein Kinases: A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Cell Line, Tumor: A cell line derived from cultured tumor cells.DiglyceridesDNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Phorbol Esters: Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Adaptor Protein Complex 3: An adaptor protein complex found primarily on perinuclear compartments.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.MaleimidesFibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Mice, Inbred C57BLPeptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Carbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Talin: A 235-kDa cytoplasmic protein that is also found in platelets. It has been localized to regions of cell-substrate adhesion. It binds to INTEGRINS; VINCULIN; and ACTINS and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton.Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.

Nitric oxide regulation of gene transcription via soluble guanylate cyclase and type I cGMP-dependent protein kinase. (1/136)

Nitric oxide (NO) regulates the expression of multiple genes but in most cases its precise mechanism of action is unclear. We used baby hamster kidney (BHK) cells, which have very low soluble guanylate cyclase and cGMP-dependent protein kinase (G-kinase) activity, and CS-54 arterial smooth muscle cells, which express these two enzymes, to study NO regulation of the human fos promoter. The NO-releasing agent Deta-NONOate (ethanamine-2,2'-(hydroxynitrosohydrazone)bis-) had no effect on a chloramphenicol acetyltransferase (CAT) reporter gene under control of the fos promoter in BHK cells transfected with an empty vector or in cells transfected with a G-kinase Ibeta expression vector. In BHK cells transfected with expression vectors for guanylate cyclase, Deta-NONOate markedly increased the intracellular cGMP concentration and caused a small (2-fold) increase in CAT activity; the increased CAT activity appeared to be from cGMP activation of cAMP-dependent protein kinase. In BHK cells co-transfected with guanylate cyclase and G-kinase expression vectors, CAT activity was increased 5-fold in the absence of Deta-NONOate and 7-fold in the presence of Deta-NONOate. Stimulation of CAT activity in the absence of Deta-NONOate appeared to be largely from endogenous NO since we found that: (i) BHK cells produced high amounts of NO; (ii) CAT activity was partially inhibited by a NO synthase inhibitor; and (iii) the inhibition by the NO synthase inhibitor was reversed by exogenous NO. In CS-54 cells, we found that NO increased fos promoter activity and that the increase was prevented by a guanylate cyclase inhibitor. In summary, we found that NO activates the fos promoter by a guanylate cyclase- and G-kinase-dependent mechanism.  (+info)

Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. (2/136)

Contraction and relaxation of smooth muscle are regulated by myosin light-chain kinase and myosin phosphatase through phosphorylation and dephosphorylation of myosin light chains. Cyclic guanosine monophosphate (cGMP)-dependent protein kinase Ialpha (cGKIalpha) mediates physiologic relaxation of vascular smooth muscle in response to nitric oxide and cGMP. It is shown here that cGKIalpha is targeted to the smooth muscle cell contractile apparatus by a leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase. Uncoupling of the cGKIalpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle cell tone.  (+info)

Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase. (3/136)

Nitric oxide (NO) and cGMP have been implicated in many neuronal functions, including regulation of gene expression, but little is known about the downstream targets of NO/cGMP in the nervous system. We found that type II cGMP-dependent protein kinase (G-kinase), which is widely expressed in the brain, mediated NO- and cGMP-induced activation of the fos promoter in cells of neuronal and glial origin; the enzyme was ineffective in regulating gene expression in fibroblast-like cells. The effect of G-kinase II on gene expression did not require calcium uptake but was synergistically enhanced by calcium. G-kinase II was membrane associated and did not translocate to the nucleus; however, a soluble G-kinase II mutant translocated to the nucleus and regulated gene expression in fibroblast-like cells. Soluble G-kinase I also regulates fos promoter activity, but membrane targeting of G-kinase I prevented the enzyme from translocating to the nucleus and regulating transcription in multiple cell types, including glioma cells; this suggests that cell type-specific factor(s) that mediate the transcriptional effects of extranuclear G-kinase II are not regulated by G-kinase I. Our results suggest that G-kinase I and II control gene expression by different mechanisms and that NO effects on neuronal plasticity may involve G-kinase II regulation of gene expression.-Gudi, T., Hong, G. K.-P., Vaandrager, A. B., Lohmann, S. M., Pilz, R. B. Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase.  (+info)

Identification of a conserved residue responsible for the autoinhibition of cGMP-dependent protein kinase Ialpha and beta. (4/136)

We isolated a constitutively active form of cGMP-dependent protein kinase Ialpha (cGK Ialpha) by PCR-driven random mutagenesis. The replacement of Ile-63 by Thr in the autoinhibitory domain results in the enhancement of autophosphorylation and the basal kinase activity in the absence of cGMP. The hydrophobicity at position 63 is essential for the inactive state of cGK Ialpha, and Ile-78 of cGK Ibeta is also required for the autoinhibitory property. Furthermore, cGK Ialpha (Ile-63-Thr) is constitutively active in vivo. These findings suggest that a conserved residue in the autoinhibitory domain was involved in the autoinhibition of both cGK Is.  (+info)

Binding and phosphorylation of a novel male germ cell-specific cGMP-dependent protein kinase-anchoring protein by cGMP-dependent protein kinase Ialpha. (5/136)

cGMP-dependent protein kinase (cGK) is a major cellular receptor of cGMP and plays important roles in cGMP-dependent signal transduction pathways. To isolate the components of the cGMP/cGK signaling pathway such as substrates and regulatory proteins of cGK, we employed the yeast two-hybrid system using cGK-Ialpha as a bait and isolated a novel male germ cell-specific 42-kDa protein, GKAP42 (42-kDa cGMP-dependent protein kinase anchoring protein). Although the N-terminal region (amino acids 1-66) of cGK-Ialpha is sufficient for the association with GKAP42, GKAP42 could not interact with cGK-Ibeta, cGK-II, or cAMP-dependent protein kinase. GKAP42 mRNA is specifically expressed in testis, where it is restricted to the spermatocytes and early round spermatids. Endogenous cGK-I is co-immunoprecipitated with anti-GKAP42 antibody from mouse testis tissue, suggesting that cGK-I physiologically interacts with GKAP42. Immunocytochemical observations revealed that GKAP42 is localized to the Golgi complex and that cGK-Ialpha is co-localized to the Golgi complex when coexpressed with GKAP42. Although both cGK-Ialpha and -Ibeta, but not cAMP-dependent protein kinase, phosphorylated GKAP42 in vitro, GKAP42 was a good substrate only for cGK-Ialpha in intact cells, suggesting that the association with kinase protein is required for the phosphorylation in vivo. Finally, we demonstrated that the kinase-deficient mutant of cGK-Ialpha stably associates with GKAP42 and that binding of cGMP to cGK-Ialpha facilitates their release from GKAP42. These findings suggest that GKAP42 functions as an anchoring protein for cGK-Ialpha and that cGK-Ialpha may participate in germ cell development through phosphorylation of Golgi-associated proteins such as GKAP42.  (+info)

Cysteine-rich protein 2, a novel substrate for cGMP kinase I in enteric neurons and intestinal smooth muscle. (6/136)

Nitric oxide/cGMP/cGMP kinase I (cGKI) signaling causes relaxation of intestinal smooth muscle. In the gastrointestinal tract substrates of cGKI have not been identified yet. In the present study a protein interacting with cGKIbeta has been isolated from a rat intestinal cDNA library using the yeast two-hybrid system. The protein was identified as cysteine-rich protein 2 (CRP2), recently cloned from rat brain (Okano, I., Yamamoto, T., Kaji, A., Kimura, T., Mizuno, K., and Nakamura, T. (1993) FEBS Lett. 333, 51-55). Recombinant CRP2 is specifically phosphorylated by cGKs but not by cAMP kinase in vitro. Co-transfection of CRP2 and cGKIbeta into COS cells confirmed the phosphorylation of CRP2 in vivo. Cyclic GMP kinase I phosphorylated CRP2 at Ser-104, because the mutation to Ala completely prevented the in vivo phosphorylation. Immunohistochemical analysis using confocal laser scan microscopy showed a co-localization of CRP2 and cGKI in the inner part of the circular muscle layer, in the muscularis mucosae, and in specific neurons of the myenteric and submucosal plexus. The co-localization together with the specific phosphorylation of CRP2 by cGKI in vitro and in vivo suggests that CRP2 is a novel substrate of cGKI in neurons and smooth muscle of the small intestine.  (+info)

Activation of cGMP-dependent protein kinase Ibeta inhibits interleukin 2 release and proliferation of T cell receptor-stimulated human peripheral T cells. (7/136)

Several major functions of type I cGMP-dependent protein kinase (cGK I) have been established in smooth muscle cells, platelets, endothelial cells, and cardiac myocytes. Here we demonstrate that cGK Ibeta is endogenously expressed in freshly purified human peripheral blood T lymphocytes and inhibits their proliferation and interleukin 2 release. Incubation of human T cells with the NO donor, sodium nitroprusside, or the membrane-permeant cGMP analogs PET-cGMP and 8-pCPT-cGMP, activated cGK I and produced (i) a distinct pattern of phosphorylation of vasodilator-stimulated phosphoprotein, (ii) stimulation of the mitogen-activated protein kinases ERK1/2 and p38 kinase, and, upon anti-CD3 stimulation, (iii) inhibition of interleukin 2 release and (iv) inhibition of cell proliferation. cGK I was lost during in vitro culturing of primary T cells and was not detectable in transformed T cell lines. The proliferation of these cGK I-deficient cells was not inhibited by even high cGMP concentrations indicating that cGK I, but not cGMP-regulated phosphodiesterases or channels, cAMP-dependent protein kinase, or other potential cGMP mediators, was responsible for inhibition of T cell proliferation. Consistent with this, overexpression of cGK Ibeta, but not an inactive cGK Ibeta mutant, restored cGMP-dependent inhibition of cell proliferation of Jurkat cells. Thus, the NO/cGMP/cGK signaling system is a negative regulator of T cell activation and proliferation and of potential significance for counteracting inflammatory or lymphoproliferative processes.  (+info)

Gene transfer of cGMP-dependent protein kinase I enhances the antihypertrophic effects of nitric oxide in cardiomyocytes. (8/136)

NO acting through soluble guanylyl cyclase and cGMP formation is a negative regulator of cardiomyocyte hypertrophy. Downstream targets mediating the inhibitory effects of NO/cGMP on cardiomyocyte hypertrophy have not been elucidated. In addition to its antihypertrophic effects, NO promotes apoptosis in cardiomyocytes, presumably through cGMP-independent pathways. We investigated the role of cGMP-dependent protein kinase (PKG) in the antihypertrophic and proapoptotic effects of NO. Incubation of neonatal rat cardiomyocytes with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) (250 micromol/L) or the PKG-selective cGMP analog 8-pCPT-cGMP (500 micromol/L) activated endogenous PKG type I, as shown by the site-specific phosphorylation of vasodilator-stimulated phosphoprotein, a well-characterized PKG substrate. SNAP (250 micromol/L) and 8-pCPT-cGMP (500 micromol/L) modestly attenuated the hypertrophic response to alpha(1)-adrenergic stimulation with phenylephrine. Although a high concentration of SNAP (1000 micromol/L) promoted apoptosis in cardiomyocytes, as evidenced by the formation of histone-associated DNA fragments, antihypertrophic concentrations of SNAP (250 micromol/L) and 8-pCPT-cGMP (500 micromol/L) did not promote cell death. Because chronic activation downregulated endogenous PKG I, we explored whether gene transfer of PKG I would enhance the sensitivity of cardiomyocytes to the antihypertrophic effects of NO/cGMP. Indeed, after adenoviral overexpression of PKG Ibeta, SNAP (250 micromol/L) and 8-pCPT-cGMP (500 micromol/L) completely suppressed the hypertrophic response to alpha(1)-adrenergic stimulation. As observed in noninfected cells, SNAP (250 micromol/L) and 8-pCPT-cGMP (500 micromol/L) did not promote apoptosis in cardiomyocytes overexpressing PKG Ibeta. Moreover, overexpression of PKG Ibeta did not enhance the proapoptotic effects of 1000 micromol/L SNAP, implying PKG-independent effects of NO on apoptosis. Endogenous PKG I mediates antihypertrophic but not proapoptotic effects of NO in a cell culture model of cardiomyocyte hypertrophy. Adenoviral gene transfer of PKG I selectively enhances the antihypertrophic effects of NO without increasing the susceptibility to apoptosis.  (+info)

GF ID PRKG1_interact #=GF AC PF15898.5 #=GF DE cGMP-dependent protein kinase interacting domain #=GF AU Eberhardt R;0000-0001-6152-1369 #=GF SE Jackhmmer:A8JNT6 #=GF GA 32.40 32.40; #=GF TC 33.30 32.50; #=GF NC 32.30 32.30; #=GF BM hmmbuild HMM.ann SEED.ann #=GF SM hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq #=GF TP Family #=GF RN [1] #=GF RM 12873707 #=GF RT Dimerization of cGMP-dependent protein kinase 1alpha and the #=GF RT myosin-binding subunit of myosin phosphatase: role of leucine #=GF RT zipper domains. #=GF RA Surks HK, Mendelsohn ME; #=GF RL Cell Signal. 2003;15:937-944. #=GF RN [2] #=GF RM 10567269 #=GF RT Regulation of myosin phosphatase by a specific interaction with #=GF RT cGMP- dependent protein kinase Ialpha. #=GF RA Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, #=GF RA Lincoln TM, Mendelsohn ME; #=GF RL Science. 1999;286:1583-1587. #=GF DR INTERPRO; IPR031775; #=GF DR SO; 0100021; polypeptide_conserved_region; #=GF CC This domain is found at the C-terminus ...
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Casein Kinase Ialpha: A casein kinase I isoenzyme that plays a role in intracellular signaling pathways including the CELL CYCLE, membrane trafficking, and RNA processing. In DROSOPHILA casein kinase Ialpha has been in regulation of Hedghog and Wingless signaling pathways. Multiple isoforms of casein kinase Ialpha exist and are due ALTERNATIVE SPLICING.
Background-The endocrine balance between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system is critical for the maintenance of arterial blood pressure and volume homeostasis. This study investigated whether a cardiac imbalance between ANP and aldosterone, towards increased mineralcorticoid receptor (MR) signaling, contributes to adverse left ventricular (LV) remodeling in response to pressure overload. Methods and Results-We used the MR-selective antagonist eplerenone to test the role of MRs in mediating pressure overload-induced dilatative cardiomyopathy of mice with abolished local, cardiac ANP activity. In response to 21-days of transverse aortic constriction (TAC), mice with cardiomyocyte-restricted inactivation (KO) of the ANP receptor (guanylyl cyclase (GC)-A) or the downstream cGMP-dependent protein kinase I (cGKI) developed enhanced LV hypertrophy and fibrosis together with contractile dysfunction. Treatment with eplerenone (100 mg/kg/day) attenuated LV ...
The expression and phosphorylation state of VASP was investigated in neutrophils during cell adherence. Adhesion is an essential process for neutrophil migration from the peripheral blood to sites of inflammation. During the process of adhesion, neutrophils adhere and spread without any clear stopping point between these two processes. Therefore, it was important to determine whether VASP was phosphorylated in response to signals involved in adhesion and/or spreading. In this report, we demonstrate that VASP is a target for cGK regulation of neutrophil spreading. We showed that VASP was in its dephosphorylated form in retracted round neutrophils and was rapidly phosphorylated by cGK at the onset of cell spreading. Both adherence and the onset of cell spreading induced significant elevations of cGMP in neutrophils. When neutrophils were incubated with 8-Br-cGMP, a direct activator of cGK, cells became more polarized in suspension, and spread more rapidly during adhesion. Our observations that ...
In addition to vasodilation, NO/NP/cGMP signaling is involved in the development of vasculoproliferative disorders, such as restenosis and atherosclerosis. The analysis of transgenic mice showed that NO can both promote58-64 and inhibit65-70 pathological vascular remodeling (see review5). This finding could explain why NO-generating drugs have not been reported to limit the progression of atherosclerosis in humans. The opposing actions of NO might depend on the magnitude and spatiotemporal profile of its production in a specific pathophysiological setting and are likely mediated through different cellular and molecular mechanisms. A key process in vascular remodeling is the phenotypic modulation of vascular SMCs from contractile to proliferating/dedifferentiated cells.71 It has been reported that NO and cGMP can both promote72,73 and inhibit74,75 the proliferation of cultured SMCs (see reviews12,76). The reason for these contradictory findings and their (patho)physiological significance is not ...
cGMP-dependent protein kinases (PKG) exhibit diverse physiological functions in the mammalian system e.g., in vascular and gastrointestinal smooth muscles, in platelets, in kidney, in bone growth, nociception and in the central nervous system. Furthermore, PKG were found in insects and in the malaria parasite Plasmodium falciparum. Two different genes of PKG exist: a) the PKG-I gene that is expressed as cytosolic PKG-Iα or PKG-Iβ isoform, and b) the PKG-II gene, which expresses the membrane associated PKG-II protein. The enzyme kinetics, the localization and the substrates of these PKG enzymes differ utilizing different physiological functions. Various inhibitors of PKG were developed directed against diverse functional regions of the kinase. These inhibitors of PKG have been used to analyse the specific functions of these enzymes. The review article will summarize these different inhibitors regarding their specificity and their present applications in vitro and in vivo. Furthermore, it will be
TY - JOUR. T1 - Identification of cGMP-Dependent protein kinase anchoring proteins (GKAPs). AU - Vo, Ngan. AU - Gettemy, Jessica M.. AU - Coghlan, Vincent M.. PY - 1998/5/29. Y1 - 1998/5/29. N2 - To promote both efficiency and selectivity, many protein kinases and phosphatases are maintained in specific subcellular microenvironments through their association with anchoring proteins. In this study, we describe a new class of proteins, called GKAPS, that specifically bind the Type II cGMP-dependent protein kinase (PKG). GKAPs were detected in rat aorta, brain, and intestine using a protein overlay technique. The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore, a synthetic peptide that blocks association of PKA with AKAPs did not affect the PKG-GKAP interaction. Deletion mutagenesis was used to map the GKAP binding determinants within PKG to the N-terminal regulatory region. While most GKAPs were tissue-specific, a ...
Cyclic GMP (cGMP) kinase is intimately involved in the regulation of vascular smooth muscle tone. Its tissue concentration was determined in normotensive and hypertensive rats by use of monospecific anti-cGMP kinase antibodies. Hearts of spontaneously hypertensive rats and renovascular (Goldblatt II) hypertensive rats contained half the concentration of cGMP kinase than those of the respective normotensive animals. The increase in blood pressure and the resulting left ventricular hypertrophy were correlated inversely with the left ventricular cGMP kinase concentration. This decrease was specific for the left ventricle and was not observed in other tissues. In addition, the cardiac concentration of cGMP kinase was unchanged in hyperthyroid animals that had comparable left ventricular hypertrophy and mild hypertension. This suggested that in severe renovascular hypertension the decrease in cardiac cGMP kinase concentration is caused by a relative lack of cardiac vessel growth during the ...
Reactivity: Chicken, Cow, Guinea Pig and more. Compare 24 different PRKG1 ELISA Kits & buy the right one directly at antibodies-online.com!
TY - JOUR. T1 - Phosphorylation of tyrosine hydroxylase by cyclic GMP - Dependent protein kinase. AU - Roskoski, R.. AU - Vulliet, Philip R. AU - Glass, D. B.. PY - 1987. Y1 - 1987. N2 - Tyrosine hydroxylase purified from rat pheochromycytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. The extent of activation was correlated with the degree of phosphate incorporated into the enzyme. Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP-dependent protein kinases. The enzymes appeared to mediate the phosphorylation of the same residue based on the observation that incorporation was not increased when both enzymes were present. The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following ...
The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015 ...
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There is growing evidence for the antitumor effects of cGMP-dependent protein kinase (PKG) in colon cancer cells. We reported recently that ectopically expressed PKG resulted in defective angiogenesis in xenografts, and was associated with reduced levels of vascular-endothelial growth factor (VEGF). In order to better understand the therapeutic potential of this enzyme, the present work has examined the mechanism of VEGF regulation by PKG. In contrast to the SW620 xenografts, PKG had no effect on VEGF expression in SW620 cells grown under standard tissue culture conditions in vitro. However, the increase in VEGF expression observed when the cells were subjected to hypoxic stress was significantly attenuated by PKG at both the mRNA and protein levels. Using luciferase reporter assays, PKG was shown to inhibit hypoxia inducible factor (HIF) transcriptional activity in several colon cancer cell lines, including SW620, HCT116, and HT29. The attenuation of HIF by PKG reflected a more fundamental ...
cAMP- and cGMP-dependent protein kinases (cAPK and cGPK). Both types of kinases contains two tandem copies of the cyclic nucleotide-binding domain. The cAPKs are composed of two different subunits: a catalytic chain and a regulatory chain which contains both copies of the domain. The cGPKs are single chain enzymes that include the two copies of the domain in their N- terminal section. The nucleotide specificity of cAPK and cGPK is due to an amino acid in the conserved region of β-barrel 7: a threonine that is invariant in cGPK is an alanine in most cAPK ...
Well ever since, DH gave me the ok to test the day of beta, I took that a little more generally. Since there have been people on here with BFPs on 5dp5dt, I …
Protein kinase G (PKG) is activated by nitric oxide (NO)-induced cGMP binding or alternatively by oxidant-induced interprotein disulfide formation. We found preactivation with cGMP attenuated PKG oxidation. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) blockade of cGMP production increased disulfide PKG to 13±2% and 29±4% of total in aorta and mesenteries, respectively. This was potentially anomalous, because we observed 2.7-fold higher NO levels in aorta than mesenteries; consequently, we had anticipated that ODQ would induce more disulfide in the conduit vessel. ODQ also constricted aorta, whereas it had no effect on mesenteries. Thus, mesenteries, but not aorta, can compensate for loss of NO-cGMP by recruiting disulfide activation of PKG. Mechanistically, this is explained by loss of cGMP allowing disulfide formation in response to basal oxidant production. Why aorta treated with ODQ generated less PKG disulfide that is insufficient to induce vasoconstriction was unclear. One potential ...
Here I describe a study of comparative behavioral genetics of a complex behavioral phenotype that is affected by a gene encoding a cGMP-dependent protein kinase (PKG, foraging). I accomplish this by using a traditional ...
Fast delivery of PRKG2 knockout Human Cell Lines for the study of gene function. Created by CRISPR/Cas9 genome editing. Includes matched wildtype control.
Dynamic regulation of arterial tone influences blood pressure and flow, and ultimately plays a critical role in cardiovascular health and disease. My research focuses primarily on cellular signaling pathways that impair excitation-contraction coupling in vascular smooth muscle (VSM), thereby reducing contractility and promoting vasodilation. In particular, I am interested in mechanisms that provide constant or tonic modulation of vascular tone by controlling membrane potential, intracellular Ca2+ and the sensitivity of the contractile apparatus to Ca2+. My projects have investigated mechanisms of cyclic nucleotide vasorelaxation, including the pivotal roles of phosphodiesterases and cyclic nucleotide dependent protein kinases. Recent studies using a novel class of cGMP-dependent protein kinase (PKG) inhibitors suggest a critical vasoregulatory role for constitutively active PKG in VSM.. The vascular endothelium (a single layer of cells lining the lumen of the entire vasculature) constantly ...
The homology-based models of binding domains in CNG channel depend heavily on the template structure of CAP and are sensitive to 1) the uncertainties inherent in defining energy terms and 2) the assumptions regarding the intricate and extensive couplings between neighboring side chains. It is therefore important to test these models, particularly the explicit predictions of prominent interactions. In one such experimental test, Thr560 in Brcng was investigated through site-directed mutagenesis and expression (Altenhofen et al., 1991). It was found that Thr560 determined the selectivity of cGMP over cAMP, a finding consistent with the interpretation of an earlier structure model of cGMP-dependent protein kinase (Weber et al., 1989). In another study, Tibbs et al. found that the highly conserved Arg559, one residue upstream of Thr560, formed a favorable ionic bond with cGMP (Tibbs et al., 1998), again agreeing with previous models. The largest shifts caused by amino acid substitutions amounted to ...
This manuscript provides novel genetic evidence for the presence of cGKIα in murine islets. We have shown that cGKIα has significant functional effects by the following main findings: 1) cGKIα is expressed in glucagon secreting α-cells and in some SST-positive δ-cells of the Langerhans islet; 2) active cGKI decreased glucagon secretion from islets at 1 mmol/l glucose; 3) active cGKI suppressed calcium oscillation in α-cells at 0.5 mmol/l glucose; and 4) serum glucose and glucagon levels were higher in the absence of islet cGKI than in CTR mice after 12-h fasting. In addition to cGKIα, we and others detected several components of the NO/cGMP and NP/cGMP pathways in mouse islets, including sGC, pGC, and PDE-5 (20,31). These findings establish cGKIα as an important signaling molecule that affects glucose metabolism in the mouse.. It has been shown that ANP inhibited glucagon and insulin release in isolated rat islets (39,40). Variable results for NO-donors and NOS inhibitors have been ...
BioAssay record AID 630202 submitted by ChEMBL: Inhibition of retinal rod CNGA1/CNGB1 expressed in Xenopus laevis oocytes assessed as blockade of cGMP-induced current at +50 mV holding potential by patch-clamp electrophysiology.
VOL. XXXVHI. COLUMBUS, TUESDAY, JULY 10, 1877. NO. 165. .1 SIEBERT &. L1LLEY, BLANK BOOK MANUFACTURERS. Printrs,BlnIer, Stationers and Legal Blank Publisher. BOOK BINDING ., . " Of every Description, by the Edition or ; Single Veiwnt. " Opera House Building :(Up Stairs), tpl COLUMBUS. GEO. T. D WALL, MERCHANT TAILOR. 157 SOUTH HIGH ST., angl7 lylp . MOODIE, HUBBARD &. CO. BANKERS, 61 SOUTH jj9tllp HIGH STREET. tatAitral OIKlv: High, Pearl mid ttaapd fit. J. M. COMI.T. W. TBANCIKO. COMLY & FRANCISCO, FUBl.I6Iir.RB AND rROPlUKTOHS. JAMES M. COJIXY. .... Editor. OFFICIAL PAPER OF THE CITY Indication jar Tennessee and the Ohio Valley Stationary or higher pressure, winds moitly from the northwest , stationary or lower temperature, partly cloudy weather, and occasional showers. - Gold closed in New York yesterday at 105. High street still presents splendid opportunities for topographical engineering. The station house question might be avoided, after all. Let each policeman be required, upon ...
Contraction of smooth muscle cells, such as those that line blood vessels, is regulated through phosphorylation of the myosin light chain. Phosphorylation by myosin light-chain kinase (and consequent increased contraction) is opposed by dephosphorylation (and consequent relaxation) catalyzed by the myosin light-chain phosphatase (PP1M). Some agents that control blood pressure act by modulating this regulatory system. Nitric oxide, a vasodilator, causes increased intracellular production of cyclic guanosine monophosphate (cGMP), which in turn activates cGMP-dependent protein kinase (cGKIα). Surks et al. provide evidence that cGKIα localizes as part of a multienzyme complex at the contractile apparatus through direct interaction with the myosin-binding subunit (MBS) of PP1M. This association was required for cGMP-dependent activation of PP1M and dephosphorylation of myosin light chain. The CGKIα enzyme adds yet another component to the cluster of regulatory components bound to the MBS, which ...
The graphic displays domains and Protease cut sites on the protein sequence. Drag your mouse right/left over the graphic. Use the selection boxes on the right to select which annotations to view simultaneously. Combine annotation with multiple checkmarks.. ...
In the present study, we have shown that YC-1 induced an antiproliferative effect in HCC cells in a concentration-dependent manner. YC-1 also inhibited DNA synthesis in HA22T cells and blocked the G1-S transition of the cell cycle. It is well known that elevation of the cGMP levels can be achieved by YC-1 through direct activation of sGC (Wu et al., 1995) and by inhibition of phosphodiesterase activity (Galle et al., 1999). Nevertheless, YC-1-mediated responses through a cGMP-independent pathway have also been described before (Ferrero and Torres, 2001; Hwang et al., 2003). In our study, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (a selective sGC inhibitor) and KT-5823 (a selective inhibitor of cGMP-dependent protein kinase) did not prevent the YC-1-induced antiproliferative effect, nor did YC-1 increase cGMP formation in HA22T cells. These results suggest that YC-1-induced inhibition of HA22T proliferation occurs through a cGMP-independent signaling pathway. Soluble guanylyl cyclase is a ...
Two disparate mechanisms have evolved for activating PKG1α; one relies on binding of the second messenger cGMP, the other involves thiol oxidation inducing a disulfide homodimer. In this study, we found that these 2 mechanisms of activating PKG1α are intricately linked with the binding of cGMP preventing oxidation to the disulfide state. The N-terminus of PKG1α, which contains the redox-sensitive cysteine from each monomer of the dimer, have been mapped using NMR.14 This structural information shows that the redox cysteines in PKG1α are in close proximity and orientated to allow the formation of a disulfide bond when oxidants are present. Our observations are consistent with cGMP binding to PKG1α causing an allosteric structural change that reorientates the redox cysteines. This reorientation presumably moves the thiols too far apart or changes their molecular environment such that their pKa is increased to lower their reactivity with oxidants, either of which would attenuate disulfide ...
Removed from the synonymy of Sphenophryne by Zweifel, 2000, Bull. Am. Mus. Nat. Hist., 253: 9, where it had been placed by Nieden, 1926, Das Tierreich, 49: 50. Revision in Zweifel, 2000, Bull. Am. Mus. Nat. Hist., 253: 1-130. Hoskin, 2004, Aust. J. Zool., 52: 240, provided a molecular tree of the Australian species. Köhler and Günther, 2008, Mol. Phylogenet. Evol., 47: 353-365, suggested that Austrochaperina is not monophyletic, with each of two monophyletic units of Austrochaperina most closely related to pieces of an equally nonmonophyletic Copiula. Hoskin, 2008, Mem. Queensland Mus., 52: 233-237, provided a key to the species of Australia. Pyron and Wiens, 2011, Mol. Phylogenet. Evol., 61: 543-583, in their study of Genbank sequences did not refute this result due to decreased taxon sampling.. ...
This study shows that in vitro exposure to high glucose (i.e., 25 mmol/L) of platelets from healthy subjects reduces the antiaggregating action of aspirin, an effect blunted by the antioxidant agent amifostine. It also shows that high glucose does not affect the ability of aspirin to inhibit thromboxane synthesis but impairs the ability of aspirin to activate the NO/cGMP/PKG pathway. Furthermore, it demonstrates that high glucose per se does not influence platelet aggregation in response to agonists, thromboxane synthesis, and the NO/cGMP/PKG pathway.. Thus, high glucose reduces the antiaggregating properties of aspirin only at very high concentrations; the extent of inhibition, although significant, is modest. In our experimental conditions, we did not observe the dramatic dose-dependent inhibition of platelet sensitivity to aspirin described by other authors (17,19).. Is it possible to translate results obtained in vitro to in vivo conditions? It is interesting to observe that the lack of ...
cAMP-dependent protein kinase complex, cytoplasm, nucleus, cAMP-dependent protein kinase activity, mitochondrion organization, protein kinase A signaling, protein phosphorylation, Ras protein signal transduction
The heart initially compensates for hypertension-mediated pressure overload by enhancing its contractile force and developing hypertrophy without dilation. Gq protein-coupled receptor pathways become activated and can depress function, leading to cardiac failure. Initial adaptation mechanisms to reduce cardiac damage during such stimulation remain largely unknown. Here we have shown that this initial adaptation requires regulator of G protein signaling 2 (RGS2). Mice lacking RGS2 had a normal basal cardiac phenotype, yet responded rapidly to pressure overload, with increased myocardial Gq signaling, marked cardiac hypertrophy and failure, and early mortality. Swimming exercise, which is not accompanied by Gq activation, induced a normal cardiac response, while Rgs2 deletion in Gαq-overexpressing hearts exacerbated hypertrophy and dilation. In vascular smooth muscle, RGS2 is activated by cGMP-dependent protein kinase (PKG), suppressing Gq-stimulated vascular contraction. In normal mice, but not ...
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"Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10". Cytogenetics and Cell ... of a novel male germ cell-specific cGMP-dependent protein kinase-anchoring protein by cGMP-dependent protein kinase Ialpha". ... 5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. PMID ... "Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1)". Genomics. ...
5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. PMID ... "Carbonic anhydrase-related protein is a novel binding protein for inositol 1,4,5-trisphosphate receptor type 1". The ... Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene. ITPR1 has been shown to ... Joseph SK, Lin C, Pierson S, Thomas AP, Maranto AR (Oct 1995). "Heteroligomers of type-I and type-III inositol trisphosphate ...
EC 2.7.11.12 Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System cGMP-Dependent Protein Kinases at the US ... Two PKG genes, coding for PKG type I (PKG-I) and type II (PKG-II), have been identified in mammals. The N-terminus of PKG-I is ... cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP ... "A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of ...
Vrolix, M; Raeymaekers, L; Wuytack, F; Hofmann, F; Casteels, R (Nov 1, 1988). "Cyclic GMP-dependent protein kinase stimulates ... L-type calcium channel expression increases in spastic vascular smooth muscle cells, which could result in excessive calcium ... "Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ... Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), ...
... inducing a signaling cascade that results in the activation of cGMP-dependent protein kinase (PKG) and an ultimate decrease in ... In addition to this, it has already been shown that NO stimulates increased cyclic GMP (cGMP) levels in the smooth muscle cells ... Various cell types play a role in HR, including astrocytes, smooth muscle cells, endothelial cells of blood vessels, and ... When these proteins are active, they turn on SREBP2 which inhibits LRP-1. LRP-1 helps the brain remove amyloid beta. Therefore ...
... where it stimulates a protein kinase called cyclic AMP-dependent protein kinase. By phosphorylating proteins, cyclic AMP- ... G proteins). The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) ... Cyclic nucleotides can be found in many different types of eukaryotic cells, including photo-receptor rods and cones, smooth ... Eckly-Michel A, Martin V, Lugnier C (September 1997). "Involvement of cyclic nucleotide-dependent protein kinases in cyclic AMP ...
In vivo phosphorylation of thromboxane by cyclic GMP-dependent protein kinase" (PDF). Journal of the Salk Institute for ... phosphorylate messengers via protein kinase A (PKA). These signaling elements include thromboxane A2, receptor type α, ... Nitric oxide (NO) stimulates cGMP production and therefore the activation cGMP-dependent protein kinase (G kinase). This kinase ... Siess, Wolfgang; Eduardo, Lapetina (1990). "Functional relationship between cyclic AMP-dependent protein phosphorylation and ...
"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... Hydrogen sulfide is also involved in the disease process of type 1 diabetes. The beta cells of the pancreas in type 1 diabetes ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ... increased cGMP triggers an increase in protein kinase G (PKG) activity. PKG reduces intracellular Ca2+ in vascular smooth ...
CNG channel activity is controlled by the interaction between cGMP-dependent protein kinase and G1 protein because of cGMP's ... "Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment". Nature. 313 (6000): 310-3. ... However, a receptor-type GC in mammalian sperm has yet to be identified. Mouse sperm express other channels such as CatSper1. ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ...
... of high gain CICR which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A ( ... causes a decrease in the stimulation of guanylate cyclase and cyclic GMP (cGMP) levels fall in vascular smooth muscle. This ... this kinase improves the Ca2+ inward current through the L-type Ca2+ channels, which leads to calcium-induced calcium release ... a special type of smooth ER) and decreasing the calcium available for contraction. In myocytes, the increase of cAMP ...
... cyclic gmp-dependent protein kinases MeSH D12.644.360.200.575 --- protamine kinase MeSH D12.644.360.250 --- cyclin-dependent ... c-type MeSH D12.644.548.587 --- pancreatic polypeptide MeSH D12.644.548.588 --- parathyroid hormone-related protein MeSH ... cyclic nucleotide-regulated protein kinases MeSH D12.644.360.200.125 --- cyclic amp-dependent protein kinases MeSH D12.644. ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 --- map kinase kinase kinase 2 MeSH D12.644.360.400.300 --- map kinase ...
"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... The vasodilating effects of sulfur dioxide are mediated via ATP-dependent calcium channels and L-type ("dihydropyridine") ... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ...
"Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... Roskoski R, Roskoski LM (Jan 1987). "Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second ... Tyrosine hydroxylase is also an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I. A consistent abnormality in ... that are phosphorylated by a variety of protein kinases. Ser40 is phosphorylated by the cAMP-dependent protein kinase. Ser19 ( ...
Cyclic GMP binds to the cGMP-dependent protein kinase (PKG1) which phosphorylates several proteins that results in decreased ... Yu, J. Y.; Kang, K. K. & Yoo, M. (2006). "Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet- ... cGMP binding proteins and protein kinase G (PKG). The effect on PKG reduces levels of calcium leading to relaxation of smooth ... Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine ...
"Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... Roskoski R, Roskoski LM (Jan 1987). "Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second ... embryonic camera-type eye morphogenesis. • social organism behavior. • cellular response to manganese ion. • response to ether ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ...
... beta-adrenergic-receptor kinase MeSH D08.811.913.696.620.682.700.150.150 --- cyclic gmp-dependent protein kinases MeSH D08.811. ... type ii MeSH D08.811.913.696.620.682.700.125 --- ca(2+)-calmodulin dependent protein kinase MeSH D08.811.913.696.620.682. ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 --- cyclic amp-dependent protein kinases ... map kinase kinase kinases MeSH D08.811.913.696.620.682.700.559.100 --- map kinase kinase kinase 1 MeSH D08.811.913.696.620.682. ...
... through a protein kinase C-dependent mechanism". Biochem J. 466 (2): 379-390. doi:10.1042/bj20140881. PMID 25422863.. ... Pugh Jr, E. N.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate ... This type of dysfunction can be seen in cardiovascular diseases, hypertension, and diabetes.[9] ... Activation of protein kinase C. Further reading: Function of protein kinase C. ...
... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... The most common bonding mode of nitric oxide is the terminal linear type (M−NO). The angle of the M−N−O group varies from 160° ... In plants, nitric oxide can be produced by any of four routes: (i) L-arginine-dependent nitric oxide synthase, (although the ... ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron regulatory factor activation. ·NO has been ...
Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). ... "STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity". Nature 461, 788-792 (8 October 2009 ... STING is also thought to activate the NF-κB transcription factor through the activity of the IκB kinase (IKK), though the ... Cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide (CDN) and the first to be found in metazoans. Other CDNs (c-di-GMP and c-di-AMP ...
Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase ... Protein splicing[edit]. Main article: Protein splicing. In addition to RNA, proteins can undergo splicing. Although the ... This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts for more than 99% of splicing. ... 3'OH of a free guanine nucleoside (or one located in the intron) or a nucleotide cofactor (GMP, GDP, GTP) attacks phosphate at ...
Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase ... can manifest as a deletion or truncation in the final protein. Splicing is catalyzed by the spliceosome, a large RNA-protein ... This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts for more than 99% of splicing. ... NAD-dependent 2'-phosphotransferase then removes the 2'-phosphate group. Splicing occurs in all the kingdoms or domains of life ...
"Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning". Nature. 423 (6943): 990-5 ... Overall, these studies show that regulating effects of netrin is dependent on the type of vascular tissue. Recently, netrin has ... DCC and UNC-5 proteins mediate netrin-1 responses. The UNC-5 protein is mainly involved in signaling repulsion. DCC, which is ... In the first pathway, the focal adhesion kinase (FAK) is bound to DCC and both undergo tyrosine phosphorylation upon netrin-1 ...
... cyclic-GMP phosphodiesterase EC 3.1.4.36: now with EC 3.1.4.43 EC 3.1.4.37: 2',3'-cyclic-nucleotide 3'-phosphodiesterase EC 3.1 ... ADP-dependent medium-chain-acyl-CoA hydrolase EC 3.1.2.20: acyl-CoA hydrolase EC 3.1.2.21: Dodecanoyl-(acyl-carrier-protein) ... type I site-specific deoxyribonuclease EC 3.1.21.4: type II site-specific deoxyribonuclease EC 3.1.21.5: type III site-specific ... protein-tyrosine-phosphatase EC 3.1.3.49: (pyruvate kinase)-phosphatase EC 3.1.3.50: sorbitol-6-phosphatase EC 3.1.3.51: ...
... excitability and protects neurons against excitotoxicity by a mechanism involving activation of receptors coupled to cyclic GMP ... His work also revealed a physiological role for the secreted form of amyloid precursor protein generated by alpha-secretase ... It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food ... Neuronal apoptosis triggered by Abeta and HNE is mediated by jun N-terminal kinase (JNK); neurons from TLR4 mutant mice exhibit ...
Cyclic GMP possibly opens cyclic nucleotide-gated (CNG) K+-selective channels, thereby causing hyperpolarization of the ... cAMP and protein kinase A as well as soluble guanylyl cyclase, cGMP, inositol trisphosphate receptor and store-operated Ca2+ ... This gradient-dependent sperm accumulation was observed over a wide temperature range (29-41°C). Since temperature affects ... They include the chemokine CCL20, atrial natriuretic peptide (ANP), specific odorants,, natriuretic peptide type C (NPPC), and ...
This structural change causes an increased affinity for the regulatory protein called transducin (a type of G protein). Upon ... Second, it serves as an adaptor protein to aid the receptor to the clathrin-dependent endocytosis machinery (to induce receptor ... As rhodopsin is phosphorylated by rhodopsin kinase (a member of the GPCR kinases(GRKs)), it binds with high affinity to the ... GMP. Reduction in cGMP allows the ion channels to close, preventing the influx of positive ions, hyperpolarizing the cell, and ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... type 1 angiotensin receptor binding. • protein complex binding. • signal transducer activity. • protein binding. • GTPase ... "Direct binding of G-protein betagamma complex to voltage-dependent calcium channels". Nature. 385 (6615): 446-50. doi:10.1038/ ... phospholipase C-activating G-protein coupled receptor signaling pathway. • retina development in camera-type eye. • Ras protein ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... which vary based on the type of cell. ... cAMP-dependent protein kinase), one of the first few kinases ... Main article: function of cAMP-dependent protein kinase. In humans, cAMP works by activating protein kinase A (PKA, ... an enzyme called protein kinase A (PKA).[12]. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ...
Proteins Protein Kinases Cyclic GMP-Dependent Protein Kinase Type II Carrier Proteins ... The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore ... The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore ... The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore ...
PKG I cyclic GMP-dependent protein kinase type I PKG U cyclic GMP-dependent protein kinase type II pM pico Molar PMSF phenyl ... and cGMP-dependent protein kinases, protein kinase C , calmodulin-dependent protein kinase U and casein kinase LT. Eur J ... Cyclic-GMP-dependent protein kinase inhibits the Ras/Mitogen-activated protein kinase pathway. Mol Cell Biol. 18:6983-94. Surks ... the residues on cyclic GMP-dependent protein kinase that are autophosphorylated in the presence of cyclic A M P and cyclic GMP ...
type. Contribution to journal publication status. published. subject. *Obstetrics, Gynecology and Reproductive Medicine ... Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue. Waldkirch, ... cavernosum, corpus, cavernous arteries, cyclic gmp, erectile dysfunction, nitric oxide, protein kinase G. in Journal of Sexual ... cyclic gmp,erectile dysfunction,nitric oxide,protein kinase G}, language = {eng}, number = {3}, pages = {536--543}, publisher ...
Neutrophils were adhered to 60-mm petri dishes in the presence of 10% human type AB serum for 10 min at 37°C. The plates were ... cyclic AMP-dependent protein kinase; cGK, cyclic GMP-dependent protein kinase; FAK, focal adhesion kinase; GBSS, Geys balanced ... VASP is a prominent substrate for both cGMP-dependent protein kinase (cGK) and cAMP-dependent protein kinase. Evidence ... Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly. J. Cell ...
Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase (By ... Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. ... 3,5-cyclic-GMP phosphodiesterase activity Source: GO_Central ,p>Inferred from Biological aspect of Ancestor,/p> ,p>A type of ... Protein. Similar proteins. Species. Score. Length. Source. P00515. cAMP-dependent protein kinase type II-alpha regulatory ...
Research Grants about cyclic gmp dependent protein kinases ... Distribution of cGMP-dependent protein kinase type I and its ... cyclic gmp dependent protein kinases. Summary. Summary: A group of enzymes that are dependent on cyclic GMP and catalyzes the ... cyclic nucleotide regulated protein kinases , cyclic gmp dependent protein kinases ... cyclic amp dependent protein kinases*enzyme inhibitors*phosphorylation*carbazoles*cyclic amp*thionucleotides*protein kinase ...
Hofmann F. The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 2005; 280: 1-4. ... Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ... cGMP-dependent protein kinase inhibits serum-response element-dependent transcription by inhibiting rho activation and ... 7-10 We have recently reported that eNOS gene transfer activates the NO/cyclic GMP (cGMP)/protein kinase G (PKG) cascade and ...
1995) Molecular characterization of type II cyclic GMP-dependent protein kinase expressed in the rat brain. J Neurochem 64:2814 ... 1993) Cloning and expression of a novel cyclic GMP-dependent protein kinase from mouse brain. J Biol Chem 268:13586-13591. ... 6,bottom). The possibility that another, unidentified cGMP-dependent protein kinase could support NO-dependent LTP can also be ... The protein kinase A inhibitor peptide PKI(6-22) (4 μm) was added to suppress cAMP-dependent protein phosphorylation. ...
... cGMP-dependent protein kinase or Protein Kinase G; GMP, guanosine triphosphate; cGMP, Cyclic guanosine monophosphate). ... Publication types, Grant support. Publication types. *Research Support, Non-U.S. Govt ... cGMP-dependent protein kinase or Protein Kinase G; GMP, guanosine triphosphate; cGMP, Cyclic guanosine monophosphate). ... cyclic monophosphate. Cells treated with between 3µM and 30µm 8-bromoguanosine 3′, 5′-cyclic monophosphate show reduced calcium ...
... cyclic GMP). The cyclic GMP, in turn, stimulates a cyclic GMP-dependent protein kinase (PKG) that leads to the anxiolytic drug ... resembles that of benzodiazepines and may be initiated at selected subunits of the gamma-aminobutyric acid type A (GABA(A)) ... which stimulates the enzyme soluble guanylyl cyclase producing the second messenger cyclic guanosine monophosphate ( ...
... inhibitory role mediated by cyclic GMP-dependent protein kinase.. F Rodriguez-Pascual, M T Miras-Portugal and M Torres ... inhibitory role mediated by cyclic GMP-dependent protein kinase.. F Rodriguez-Pascual, M T Miras-Portugal and M Torres ... inhibitory role mediated by cyclic GMP-dependent protein kinase.. F Rodriguez-Pascual, M T Miras-Portugal and M Torres ... inhibitory role mediated by cyclic GMP-dependent protein kinase. Message Subject (Your Name) has forwarded a page to you from ...
The level of myosin II phosphorylation is determined by activities of myosin light chain kinase and myosin phosphatase (MP). MP ... EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/Protein Phosphatase 1; ... Muscle Proteins / genetics, metabolism. Muscle, Smooth / enzymology*. Myosin Type II / chemistry, genetics, metabolism*. Myosin ... Cyclic GMP-Dependent Protein Kinases / genetics, metabolism. Gene Expression Regulation, Developmental. Humans. Membrane ...
"Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10". Cytogenetics and Cell ... of a novel male germ cell-specific cGMP-dependent protein kinase-anchoring protein by cGMP-dependent protein kinase Ialpha". ... 5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. PMID ... "Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1)". Genomics. ...
5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. PMID ... "Carbonic anhydrase-related protein is a novel binding protein for inositol 1,4,5-trisphosphate receptor type 1". The ... Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene. ITPR1 has been shown to ... Joseph SK, Lin C, Pierson S, Thomas AP, Maranto AR (Oct 1995). "Heteroligomers of type-I and type-III inositol trisphosphate ...
The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth ... This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, ... nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. ... Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act ...
Stimulation of cyclic GMP-dependent protein kinase leads to phosphorylation of type I inositol trisphosphate-receptor in rat ... The isolated IP3 receptor protein was phosphorylated by both cAMP- and cGMP-dependent protein kinases on two distinct sites as ... 175, 192-198). Phosphopeptide maps show that cAMP-dependent protein kinase (PKA) labeled both sites with the same time course ... whereas cGMP-dependent protein kinase (PKG) phosphorylated Ser-1756 with a higher velocity and a higher stoichiometry than Ser- ...
... two cyclic nucleotide phosphodiesterase inhibitors, when fed to wild-typeDrosophila adults, cause the rapid d ... 1989). Ca2+-dependent proteolytic modification of the cAMP-dependent protein kinase in Drosophila wild type and dunce memory ... Radioimmunoassay of cyclic AMP and cyclic GMP.Adv. Cyclic Nucl. Res. 10:2-33. ... Buxbaum, J. D., and Dudai, Y. (1989). A quantitative model for the kinetics of cAMP-dependent protein kinase (type II) activity ...
... Mammals have three different isoforms of cyclic GMP-dependent ... cGMP-dependent protein kinase 1-like , cGMP dependent protein kinase type 1 , protein kinase, cGMP-dependent, regulatory, type ... cGMP-dependent protein kinase 1 , protein kinase, cGMP-dependent, type I , cGMP-dependent protein kinase 1, beta isozyme , cGMP ... cGMP-dependent protein kinase I , cGK 1 , PKG1 alpha , cGMP-dependent protein kinase type 1 alpha , cGMP-dependent protein ...
Cyclic GMP-Dependent Protein Kinases Nitric Oxide Synthase Type I Response Elements ... our estrogen proposal of the signaling pathway of cGMP-dependent protein kinase (PKG) in mediating estrogen-induced ... our estrogen proposal of the signaling pathway of cGMP-dependent protein kinase (PKG) in mediating estrogen-induced ... our estrogen proposal of the signaling pathway of cGMP-dependent protein kinase (PKG) in mediating estrogen-induced ...
... and ASTRAL compendium for protein structure and sequence analysis ... Cyclic GMP, Cyclic GMP-Dependent Protein Kinase Type II, ... Compound: cGMP-dependent protein kinase 1. Species: Homo sapiens [TaxId:9606]. Gene: PRKG1, PRKG1B, PRKGR1A, PRKGR1B. Database ... Compound: cGMP-dependent protein kinase 1. Species: Homo sapiens [TaxId:9606]. Gene: PRKG1, PRKG1B, PRKGR1A, PRKGR1B. Database ... Description: PKG Is Carboyl Terminal Cyclic Nucleotide Binding Domain (CNB-B) in a complex with 8-pCPT-cGMP. Class: protein ...
... cAMP and cGMP-dependent protein kinases (PKA/PKG). Displays site selectivity for Site B of cAMP-dependent PKA type II. Potently ... 8-(4-Chlorophenyl)thio-cyclic AMP is a potent inhibitor of the cyclic GMP-specific phosphodiesterase (PDE VA).. Biochem ... By product type. Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex ... By product type. Primary antibodies. Secondary antibodies. ELISA, Matched Antibody Pairs and Multiplex Immunoassays. Cell and ...
... activated guanylate cyclases that generate the secondary signaling molecule cyclic guanosine monophosphate (cGMP) in the ... activated guanylate cyclases that generate the secondary signaling molecule cyclic guanosine monophosphate (cGMP) in the ... Primary open-angle glaucoma (POAG) is the most common type of glaucoma. Elevated intraocular pressure (IOP) is currently the ... Primary open-angle glaucoma (POAG) is the most common type of glaucoma. Elevated intraocular pressure (IOP) is currently the ...
cAMP- and cyclic GMP-dependent protein kinases (PKA and PKG) phosphorylate RhoA on Ser188.4,5 Both in vitro and in vivo ... Ste20-related kinase SLK phosphorylates Ser188 of RhoA to induce vasodilation in response to angiotensin II Type 2 receptor ... Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ... MAPKAP kinase-2; a novel protein kinase activated by mitogen-activated protein kinase. Embo J. 1992;11:3985-3994. ...
GMP, 54364-02-2; Calcium Channels; Cell Adhesion Molecules; Cyclic GMP, 7665-99-8; Cyclic GMP-Dependent Protein Kinases, EC 2.7 ... In the present study, the presence of cGMP-dependent protein kinase (cGMP-PK) immunoreactivity and activity in various types of ... Cyclic GMP · Cyclic GMP-Dependent Protein Kinases · Cytoplasm · Endothelium, Vascular · Enzyme Activation · Hemostasis · Human ... cyclic GMP · calcium ion · cyclic GMP · cyclic GMP derivative · fura 2 · horseradish peroxidase · phosphoprotein · protein ...
In human myotubes, NP induced PGC-1α and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment ... Natriuretic peptides/cGMP/cGMP-dependent protein kinase cascades promote muscle mitochondrial biogenesis and prevent obesity. ... biological responses are largely mediated through cyclic GMP (cGMP) produced by the guanylyl cyclase domain of NP receptor type ... They promote a rapid and sustained rise of intracellular cGMP that activates a cGMP-dependent protein kinase, PRKG1, which then ...
  • abstract = "To promote both efficiency and selectivity, many protein kinases and phosphatases are maintained in specific subcellular microenvironments through their association with anchoring proteins. (elsevier.com)
  • Bioactivatable, membrane-permeant analogs of cyclic nucleotides as biological tools for growth control of C6 glioma cells. (abcam.com)
  • Moreover, Sp1 binding activity on the PKG-Iα promoter was detected in A7r5 cells, and this binding was inhibited by NO and cyclic nucleotides. (elsevier.com)
  • The elevation of these two platelet cyclic nucleotides interferes with platelet activatory signalling pathways such as the intracellular Ca 2+ elevation and the reorganization of the cytoskeleton. (oatext.com)
  • The authors review what is known about the deleterious effects of sickling on the genitourinary tract and how the role of cyclic nucleotides signaling and protein kinases may help understand the pathophysiology underlying these manifestations and develop novel therapies in the setting of urogenital disorders in sickle cell disease. (hindawi.com)
  • This paper focuses on how previous, sometimes poorly explained, clinical observations of urogenital disorders in patients with SCD relate to more recent discoveries on the role of cyclic nucleotides and protein kinases in the pathophysiology of sickle vaso-occlusion. (hindawi.com)
  • In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. (lu.se)
  • less thanbrgreater than less thanbrgreater thanIn the smooth muscle portion of the transition zone, immunosignals specific for the PDE5 were found co-localized with cyclic GMP, cGKI alpha, and cGKI, as well as with the cyclic cAMP-binding protein kinase A. Smooth muscle bundles were seen innervated by slender varicose nerves characterized by the expression of nNOS. (diva-portal.org)
  • In the vasculature, RhoA and its downstream effector Rho associated protein kinase (Rock) have been shown to regulate processes such as vascular smooth muscle cell (VSMC) contraction, proliferation and differentiations, endothelial permeability, platelet activation, and leukocyte migration. (ahajournals.org)
  • This modulation requires cyclic GMP synthesis via nitric oxide synthase (NOS)-NO stimulation, but upstream and downstream mechanisms remain un-defined. (springer.com)
  • We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. (ntu.edu.sg)
  • Analysis of second messenger signaling downstream of PI(4,5)P 2 hydrolysis, specifically mediation of intracellular Ca 2+ -signaling by IP 3 receptor-binding protein released with inositol 1,4,5-trisphosphate. (bates.edu)
  • Knockout mice for VASP have a defect in cyclic nucleotide-mediated platelet disaggregation and integrin αΙΙbβ3 activation ( 13 , 14 ). (jimmunol.org)
  • Another plasma cell malignancy, multiple myeloma (MM), arising spontaneously in the ageing C57BL/KaLwRij mice, was investigated in order to see whether the MM cells contain c-myc abnormalities of the MPC or RIC type. (tudelft.nl)
  • Ex vivo, ovariectomy leads to an increase in the amplitude of phenylephrine- or serotonine-induced contractions of aortic rings in wild-type mice but not in AMPKα1-knock-out mice or E2-supplemented animals. (ahajournals.org)
  • Tissue excised from KI mice showed impaired relaxation to H2S compared with that from their wild-type littermates. (bl.uk)
  • These KI mice express a 'trapping mutant' form of Trx that becomes covalently linked to proteins with oxidised thiol after H2O2 or H2S treatment. (bl.uk)
  • The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of GC-A (EC GC-A KO) or with deleted caveolin-1 (cav-1), the caveolae scaffold protein. (uni-wuerzburg.de)
  • In contrast, a fraction of wild type (37.5%), TNF deficient (12.5%), and TNFR2 deficient mice (22.2%) were able to fully reject the tumor within two weeks. (uni-wuerzburg.de)
  • TAT-apoptosis repressor with caspase recruitment domain protein transduction rescues mice from fulminant liver failure. (mdc-berlin.de)
  • Transretinal and single-cell rod electrophysiological recordings were obtained from several strains of mice expressing GRK1 at 0.3- to 3-fold the wild-type levels. (arvojournals.org)
  • Thbs2 −/− mice, which lack normal TSP2 mRNA and protein, were produced with the expected Mendelian frequency, were normal in appearance, and reproduced normally. (rupress.org)
  • p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene. (uniprot.org)
  • Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene. (wikipedia.org)
  • We thus proposed that the estrogen-mediated gene induction of Trx plays a pivotal role in the promotion of neuroprotection because Trx is a multifunctional antioxidative and antiapoptotic protein. (elsevier.com)
  • In this study, the mechanisms of human type I PKG-α (PKG-Iα) gene expression were examined. (elsevier.com)
  • The hCHGA gene is located on chromosome 14q32.12, which spans 12,192 bp and gives rise to a transcript of 2,041 bp that encodes a 439-amino acid (aa) mature protein ( 85 ). (physiology.org)
  • Division of labor in honey bee colonies is influenced by the foraging gene ( Amfor ), which encodes a cGMP-dependent protein kinase (PKG). (biologists.org)
  • Transcription regulation mechanism of the syntaxin 1A gene via protein kinase A Syntaxin 1A (Stx1a) is primarily involved in the docking of synaptic vesicles at active zones in neurons. (medworm.com)
  • Cyclic nucleotide PDEs consist of 10 gene families, each having one or more isoforms. (aacrjournals.org)
  • The ligand-binding domains of cyclic nucleotide-gated (CNG) channels show sequence homology to corresponding region(s) of the Escherichia coli catabolite gene-activator protein (CAP) and to the regulatory subunit of cAMP-dependent or cGMP-dependent protein kinases. (aspetjournals.org)
  • The critical role of RhoA/Rho-kinase signaling in various systems is discussed, in particular those vascular smooth muscle disorders involving hypercontractility. (biomedsearch.com)
  • Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. (ntu.edu.sg)
  • We identify the orphan hybrid histidine kinase SgmT as the partner kinase of DigR. (unibas.ch)
  • Moreover, diabetes is coupled with lower melatonin levels as reduction in serum melatonin and higher insulin level is observed in type 2 diabetic Goto Kakizaki rats ( 6 ). (scielo.br)
  • K ir 2.1 mRNA and protein could be identified in basilar arteries of rats and dogs [ 7 , 8 ], whereas the presence of K ATP in cerebrovascular smooth muscle has been determined electrophysiologically [ 9 ] and reviewed in detail by Ploug et al. (hindawi.com)
  • Cytosolic DNA induces type I interferons and other cytokines that are important for antimicrobial defense but can also result in autoimmunity. (sciencemag.org)
  • After viral infection, ELF4 binds to TMEM173 (STING) and induces type I interferon. (innatedb.ca)
  • Bir süre sonra cgmp fosfodiesteraz tip 5 (PDE5) enzimi tarafından yıkılarak inaktif form olan 5 -GMP ye çevrilir. (biz.tr)
  • VASP is believed to play an important role in controlling the cytoskeletal organization because it binds filamentous actin (F-actin) and profilin, a protein that forms complexes with G-actin and regulates actin dynamics ( 2 , 11 , 12 ). (jimmunol.org)
  • section describes a region in the protein which binds nucleotide phosphates. (uniprot.org)
  • Definition: a protein that binds a ligand with high affinity and low capacity. (slideserve.com)
  • The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. (ntu.edu.sg)
  • We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. (ntu.edu.sg)
  • The GGDEF domain binds the second messenger bis-(3'-5')-cyclic-dimeric-GMP (c-di-GMP) and functions as a c-di-GMP receptor to spatially sequester SgmT. (unibas.ch)
  • The negative inotropism was insensitive to losartan and CGP42112 (AT 1 and AT 2 ANG II receptor antagonists, respectively), and was abrogated by the AT 1 receptor antagonist CV11974, the G protein blocker pertussis toxin (PTx) and the muscarinic antagonist atropine. (biologists.org)
  • Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility. (readbyqxmd.com)
  • cAMP is a partial agonist for PKG , and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo (show C9orf3 ELISA Kits ), cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. (antibodies-online.com)
  • Taken together, these observations suggest that the association of CAIN with intracellular domains involved in mGluR/G protein coupling provides an additional mechanism by which Group I mGluR endocytosis and signaling are regulated. (researchwithnj.com)
  • Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. (ntu.edu.sg)
  • The mechanism of dense granule secretion involves the G kinase-dependent association of syntaxin 2 with vesicle-associated membrane protein 3. (rupress.org)
  • cGMP signaling is abrogated by cGMP hydrolysis via PDEs and cGMP export via multidrug resistance proteins (also referred to as ABC transporters). (springer.com)
  • X-ray cocrystal structures of certain PDEs and catalytic products (5′-GMP or 5′-AMP) contain these bonds (in PDE11A4, Gln-869 would be the contact amino acid), but cocrystal structure of a PDE with a CN has not been determined. (aspetjournals.org)