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 126.96.36.199.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)Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.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.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.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 188.8.131.52.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.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 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)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.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.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.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.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.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.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.Kinetics: The rate dynamics in chemical or physical systems.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.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.OxadiazolesEnzyme 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.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.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.Guanylate Kinase: Catalyzes the ATP-dependent PHOSPHORYLATION of GMP to generate GDP and ADP.Nucleotides, CyclicAmino 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.Guanylate Cyclase-Activating Proteins: Neuronal calcium sensor proteins that regulate the activation of membrane-bound GUANYLATE CYCLASE. They are primarily expressed in the RETINA where they play an important role in PHOTOTRANSDUCTION.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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).Nitroprusside: 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.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.PurinonesMAP 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.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.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.Nitric Oxide Donors: A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)Receptors, Guanylate Cyclase-Coupled: A class of cellular membrane receptors that either have an intrinsic guanylate cyclase activity or are closely coupled to specific guanylate cyclases within the cell.eIF-2 Kinase: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Protein 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.Receptors, Atrial Natriuretic Factor: Cell surface proteins that bind ATRIAL NATRIURETIC FACTOR with high affinity and trigger intracellular changes influencing the behavior of cells. They contain intrinsic guanylyl cyclase activity.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.Quinoxalines3',5'-Cyclic-GMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.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.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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Natriuretic Peptides: Peptides that regulate the WATER-ELECTROLYTE BALANCE in the body, also known as natriuretic peptide hormones. Several have been sequenced (ATRIAL NATRIURETIC FACTOR; BRAIN NATRIURETIC PEPTIDE; C-TYPE NATRIURETIC PEPTIDE).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)Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.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.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.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.Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Enzyme Activators: Compounds or factors that act on a specific enzyme to increase its activity.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.PhosphoproteinsJNK 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.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.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)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.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position.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 KINASESSerine: 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.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Nucleoside-Phosphate Kinase: An enzyme that catalyzes reversible reactions of a nucleoside triphosphate, e.g., ATP, with a nucleoside monophosphate, e.g., UMP, to form ADP and UDP. Many nucleoside monophosphates can act as acceptor while many ribo- and deoxyribonucleoside triphosphates can act as donor. EC 184.108.40.206.1-(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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.Protamine Kinase: An aspect of protein kinase (EC 220.127.116.11) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.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.Aminoquinolines: Quinolines substituted in any position by one or more amino groups.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.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.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.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.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.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.Protein Kinase C beta: PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.Cyclic 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.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.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.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.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.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.Adenylate Cyclase Toxin: One of the virulence factors produced by virulent BORDETELLA organisms. It is a bifunctional protein with both ADENYLYL CYCLASES and hemolysin components.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.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.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.Manganese: A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.IndazolesCarrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.S-Nitroso-N-Acetylpenicillamine: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.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.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.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.Sulfonamides: A group of compounds that contain the structure SO2NH2.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.Rod Cell Outer Segment: The portion of a retinal rod cell situated between the ROD INNER SEGMENT and the RETINAL PIGMENT EPITHELIUM. It contains a stack of photosensitive disk membranes laden with RHODOPSIN.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.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.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.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.Arginine: An essential amino acid that is physiologically active in the L-form.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.Nitroso CompoundsCarbazoles: Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.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.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.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.Molsidomine: A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS.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.Thionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.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).Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE 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).Aorta, Thoracic: The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.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.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.Photoreceptor Cells: Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.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.Cyclic Nucleotide Phosphodiesterases, Type 5: A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)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.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.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.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.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.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.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.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.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.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)Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.S-Nitrosoglutathione: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.Aorta: The main trunk of the systemic arteries.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.Receptors, Peptide: Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.Mice, Inbred C57BLSirtuin 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.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.DiglyceridesPhorbol 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.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.Nitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)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.Cell Line, Tumor: A cell line derived from cultured tumor cells.omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase.Natriuretic Peptide, C-Type: A PEPTIDE of 22 amino acids, derived mainly from cells of VASCULAR ENDOTHELIUM. It is also found in the BRAIN, major endocrine glands, and other tissues. It shares structural homology with ATRIAL NATRIURETIC FACTOR. It has vasorelaxant activity thus is important in the regulation of vascular tone and blood flow. Several high molecular weight forms containing the 22 amino acids have been identified.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Nerve Tissue Proteins
... cyclic GMP) from guanosine triphosphate (GTP). The soluble cGMP activates cyclic nucleotide-dependent protein kinase G (PKG or ... NO diffuses into the smooth muscle cells of the blood vessel and interacts with soluble guanylate cyclase. Nitric oxide ... PKG is a kinase that phosphorylates a number of proteins that regulate calcium concentrations and calcium sensitization, ... The neuronal enzyme (NOS-1) and the endothelial isoform (NOS-3) are calcium-dependent and produce low levels of this gas as a ...
cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein kinase G) is a dimer consisting ... Guanylate cyclase (GC) catalyzes cGMP synthesis. This enzyme converts GTP to cGMP. Peptide hormones such as the atrial ... Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are cGMP ... cyclic monophosphate (8-Br-cGMP) Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: ...
Protein kinase activationEdit. cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein ... Guanylate cyclase (GC) catalyzes cGMP synthesis. This enzyme converts GTP to cGMP. Peptide hormones such as the atrial ... cGMP; 3',5'-cyclic GMP; Guanosine cyclic monophosphate; Cyclic 3',5'-GMP; Guanosine 3',5'-cyclic phosphate ... Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP ...
... cyclic gmp-dependent protein kinases MeSH D12.644.360.200.575 --- protamine kinase MeSH D12.644.360.250 --- cyclin-dependent ... sos1 protein MeSH D12.644.360.350 --- guanylate cyclase MeSH D12.644.360.375 --- heterotrimeric gtp-binding proteins 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 ...
... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... It relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase ... In plants, nitric oxide can be produced by any of four routes: (i) L-arginine-dependent nitric oxide synthase, (although the ... activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron ...
While studying cyclic GMP, Ignarro read a paper by Ferid Murad, who demonstrated that nitric oxide elevates cyclic GMP levels. ... Guanylate cyclase from bovine lung: a kinetic analysis of the regulation of the purified soluble enzyme by protoporphyrin IX, ... Role of p42/p44 mitogen-activated protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell ... Rapid nitric oxidemediated S-nitrosylation of estrogen receptor: Regulation of estrogen-dependent gene transcription. Proc. ...
... causes a decrease in the stimulation of guanylate cyclase and cyclic GMP (cGMP) levels fall in vascular smooth muscle. This ... of high gain CICR which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A ( ... In myocytes, the increase of cAMP concentration increases in turn the activity of PKA: this kinase improves the Ca2+ inward ... PKA) and Ca2+ calmodulin kinase pathways. Increases cardiac contractility, vasodilator. Acts by inhibiting the breakdown of ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... function of cAMP-dependent protein kinase. In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein ... In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein- ... an enzyme called protein kinase A (PKA).. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ...
CNG channel activity is controlled by the interaction between cGMP-dependent protein kinase and G1 protein because of cGMP's ... Speract activates a receptor-type guanylate cyclase (GC) and stimulates a rise in intracellular cGMP concentrations. Speract ... "Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment". Nature. 313 (6000): 310-3. ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ...
... stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), ... Vrolix, M; Raeymaekers, L; Wuytack, F; Hofmann, F; Casteels, R (Nov 1, 1988). "Cyclic GMP-dependent protein kinase stimulates ... "Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular ... including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to ...
"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron ... 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 ...
The synthesised cGMP acts as a secondary messenger and activates cGMP-dependent protein kinase (protein kinase G) to regulate ... NO binds to soluble guanylate cyclase (sGC) and mediates the synthesis of the secondary messenger cyclic guanosine ... reducing cyclic GMP degradation. Endothelin receptor antagonist, another class of drugs used in PAH "Background Riociguat". ... Stasch JP, Hobbs AJ (2009). "NO-independent, haem-dependent soluble guanylate cyclase stimulators". Handbook of Experimental ...
... guanylate (cyclic di-GMP). Degradation of cyclic di-GMP to guanosine monophosphate (GMP) is catalyzed by a phosphodiesterase ( ... "Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain". ... In enzymology, diguanylate cyclase, also known as diguanylate kinase (EC 18.104.22.168), is an enzyme that catalyzes the chemical ... Often, GGDEF domains with DGC activity are found in the same proteins as c-di-GMP-specific phosphodiesterase (PDE) EAL (Glu-Ala ...
... cyclic-GMP phosphodiesterase EC 22.214.171.124: now with EC 126.96.36.199 EC 188.8.131.52: 2',3'-cyclic-nucleotide 3'-phosphodiesterase EC 3.1 ... ADP-dependent medium-chain-acyl-CoA hydrolase EC 184.108.40.206: acyl-CoA hydrolase EC 220.127.116.11: Dodecanoyl-(acyl-carrier-protein) ... cyclic-guanylate-specific phosphodiesterase EC 18.104.22.168: 3',5'-cyclic-AMP phosphodiesterase EC 22.214.171.124: N- ... protein-tyrosine-phosphatase EC 126.96.36.199: (pyruvate kinase)-phosphatase EC 188.8.131.52: sorbitol-6-phosphatase EC 184.108.40.206: ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Ca2+/calmodulin-dependent protein kinases or CaM kinases. are primarily regulated by the Ca2+/calmodulin complex. ... Protein kinase C ('PKC'). is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three ... Dephospho-(reductase kinase) kinase (EC 220.127.116.11). *AMP-activated protein kinase α *PRKAA1 ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... see MAP kinase pathway. Calcium. *Intracellular calcium-sensing proteins. *Calcineurin. *Ca2+/calmodulin-dependent protein ... GTP-binding protein regulators regulate G proteins in several different ways. Small GTPases act as molecular switches in ... and thus requires another class of regulatory proteins to accelerate this activity, the GTPase activating proteins (GAPs). ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... see MAP kinase pathway. Calcium. *Intracellular calcium-sensing proteins. *Calcineurin. *Ca2+/calmodulin-dependent protein ... Ser/Thr-specific protein phosphatases are regulated partly by their location within the cell and by specific inhibitor proteins ... Protein serine/threonine phosphatase (PSP) is a form of phosphoprotein phosphatase that acts upon phosphorylated serine/ ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Guanylate cyclase (EC 18.104.22.168, also known as guanyl cyclase, guanylyl cyclase, or GC) is a lyase enzyme. Guanylate cyclase is ... soluble guanylate cyclase) forms of guanylate cyclases. Membrane bound guanylate cyclases include an external ligand-binding ... Guanylyl cyclase activator (protein). References. *^ Sakurai K.; Chen J.; Kefalov V. (2011). "Role of guanylate cylcase ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... "Direct binding of G-protein betagamma complex to voltage-dependent calcium channels". Nature. 385 (6615): 446-50. doi:10.1038/ ... protein complex binding. • signal transducer activity. • protein binding. • GTPase activity. • GTPase binding. • G-protein ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Cyclins, when bound with the dependent kinases, such as the p34/cdc2/cdk1 protein, form the maturation-promoting factor. MPFs ... is a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (CDK ... Nurse won the 2001 Nobel Prize in Physiology or Medicine for their discovery of cyclin and cyclin-dependent kinase. ...
Guanylate cyclase. *cGMP. *3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... Types of G protein signaling. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ...
... beta-adrenergic-receptor kinase MeSH D08.811.913.696.620.682.700.150.150 --- cyclic gmp-dependent protein kinases MeSH D08.811. ... adenylate cyclase MeSH D08.811.520.650.200.040 --- adenylate cyclase toxin MeSH D08.811.520.650.600 --- guanylate cyclase MeSH ... 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. ...
Research Grants about cyclic gmp dependent protein kinases ... guanylate cyclase*cyclic amp dependent protein kinases*enzyme ... 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 ... Toxoplasma gondii cyclic GMP-dependent kinase: chemotherapeutic targeting of an essential parasite protein kinase. Robert G K ...
Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice.2000In: Proceedings of the National Academy of Sciences of ... NO activates soluble guanylate cyclase, which leads to the production of cyclic GMP (cGMP). cGMP signals via three different ... In addition, two different cGMP-dependent protein kinases (cGKI and cGKII) have been identified in mammals (6, 7). cGKII is ... Erectile dysfunction in cyclic CMP-dependent kinase I-deficient mice2000In: Proceedings of the National Academy of Sciences of ...
... cyclic GMP) from guanosine triphosphate (GTP). The soluble cGMP activates cyclic nucleotide-dependent protein kinase G (PKG or ... NO diffuses into the smooth muscle cells of the blood vessel and interacts with soluble guanylate cyclase. Nitric oxide ... PKG is a kinase that phosphorylates a number of proteins that regulate calcium concentrations and calcium sensitization, ... The neuronal enzyme (NOS-1) and the endothelial isoform (NOS-3) are calcium-dependent and produce low levels of this gas as a ...
... and heat-stable enterotoxin activate guanylate cyclase C and/or a pertussis toxin-sensitive G protein in human proximal tubule ... Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile ... Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene ... Cyclic GMP-Dependent Protein Kinases. Genes and Proteins. cGKs are serine/threonine kinases that are present in a variety of ...
... 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 ... cGMP interacts with a variety of effector proteins including cGMP-dependent protein kinases (PKGs), cGMP-regulated ... Figure 1. Schematic of the Cyclic GMP (cGMP) signaling pathway. cGMP is synthesized from GTP by soluble guanylate cyclases (sGC ...
Natriuretic peptide receptor A/guanylate cyclase A; PKG, cGMP-dependent protein kinase or Protein Kinase G; GMP, guanosine ... 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 monophosphate. Cells treated with 100µm 8-bromoguanosine 3′, 5′-cyclic monophosphate, show reduced calcium influx. (d) A ...
NO activates soluble guanylate cyclase, which leads to the production of cyclic GMP (cGMP). cGMP signals via three different ... In addition, two different cGMP-dependent protein kinases (cGKI and cGKII) have been identified in mammals (6, 7). cGKII is ... Erectile dysfunction in cyclic CMP-dependent kinase I-deficient mice. Hedlund, Petter Lund University Hospital. ... Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora ...
... are capable of modulating the bodys production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the ... intracellular messenger which triggers a multitude of different effects via the modulation of cGMP-dependent protein kinases, ... Cyclic GMP (cGMP) is an important ... Soluble guanylate cyclase activators Abstract. A compound of ... The soluble guanylate cyclases ("sGC"), which are cytosolic heterodimeric heme proteins, in contrast, are essentially regulated ...
... and also after NO-dependent activation of the soluble guanylate cyclase. The relative contributions of ANP- and NO-modulated ... We designed duplex siRNA constructs to target GC-A, VASP, and cyclic GMP-dependent protein kinase (PKG). Transfection of BAEC ... Cyclic GMP is synthesized in endothelial cells following ANP activation of the particulate guanylate cyclase GC-A, ... Abstract 454: siRNA-mediated Selective Targeting of Signaling Proteins Reveals that ANP Differentially Modulates Cyclic GMP ...
Experimental Parkinsonism, Soluble Guanylate Cyclase, Cyclic GMP-Dependent Protein Kinases, Cyclic GMP, Corpus striatum ... cGMP-protein kinase G (PKG) signaling cascade. Converging evidence from animal models indicates that dysregulation of striatal ... One relatively understudied yet promising candidate for second messenger-based therapies is the soluble guanylyl cyclase (sGC)- ...
NO increases cyclic GMP by activating guanylate cyclase, which in turn activates potassium channels. This results in ... While its action on endothelin-A receptors results in vasoconstriction through activation of protein kinase and increase in ... Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell diseaseProc Natl Acad Sci U S AYear: ... NO synthase activity is reduced and as a result nitric oxide driven cyclic GMP production via Guanylate Cyclase is also reduced ...
... of the control c-GMP production. Inhibition of protein kinase C by 50 microM H-7 does not significantly attenuate the H1- ... indicating the involvement of a nitric oxide-dependent activation of soluble guanylate cyclase. This suggestion is supported by ... Histamine H1-receptor-mediated cyclic GMP production in guinea-pig lung tissue is an L-arginine-dependent process.. Leurs R1, ... This nitric oxide production is finally responsible for the activation of soluble guanylate cyclase, leading to the production ...
... and by cyclic GMP-dependent kinase (Seidler et al., 1997). Ca2+-mobilizing receptors are known to activate protein kinase C, to ... Moreover, Ca2+-mobilizing agents promoted activation of guanylate cyclase in specialized epithelia, e.g., enterocytes ( ... Chaudhuri et al., 1998), and a functional CFTR protein was required for mouse intestinal calcium- and cyclic GMP-dependent ... Although CFTR is a cyclic AMP-activated Cl− channel, it is also activated by protein kinase C (Jia et al., 1997) ...
Resistant against mammalian cyclic nucleotide-dependent phosphodiesterases, no metabolic side effects. Significantly more ... Inhibitor of protein kinase G I α and I β. ... "A Novel Cyclic GMP-dependent Protein Kinase is Expressed in the ... "Long-Term Potentiation in Hippocampus Involves Sequential Activation of Soluble Guanylate Cyclase, cGMP-dependent Protein ... Layland J., Li J. M.Shah A. M., J. Physiol.-London, 540, 457 - 467 (2002), "Role of Cyclic GMP-dependent Protein Kinase in the ...
guanylate cyclase 1 * Cyclic GMP-Dependent Protein Kinase Type I * Heme Oxygenase (Decyclizing) ...
cGMP-dependent protein kinase * guanylate cyclase * cyclic GMP * nitric oxide * embryogenesis 16 Citations (Scopus) ... Expression and function of cGMP-dependent protein kinase type I during medaka fish embryogenesis. Yamamoto, T. & Suzuki, N., ... Promoter activity of the 5′-flanking regions of medaka fish soluble guanylate cyclase α1 and β subunit genes. Yamamoto, T. & ... Genomic Structure and Expression of the Soluble Guanylyl Cyclase α2 Subunit Gene in the Medaka Fish Oryzias latipes. Yao, Y., ...
Cyclic GMP-Dependent Protein Kinases -- genetics. Genetic Markers. Guanylate Cyclase -- genetics. In Situ Hybridization, ...
A Short History of cGMP, Guanylyl Cyclases, and cGMP-Dependent Protein Kinases ... Cyclic GMP-Hydrolyzing Phosphodiesterases Sharron H. Francis, Jackie D. Corbin, Erwin Bischoff ... NO- and Haem-Independent Soluble Guanylate Cyclase Activators Harald H. H. W. Schmidt, Peter M. Schmidt, Johannes-Peter Stasch ... addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and ...
... dendrite growth is stunted by inhibition of nitric oxide-dependent activation of soluble guanylyl cyclase and protein kinase G ... 2001) Soluble guanylate cyclase is required during development for visual system function in Drosophila. J Neurosci 21:7705- ... 2005) Cyclic GMP-dependent protein kinase regulates CCAAT enhancer-binding protein beta functions through inhibition of ... 2003) Hippocampal cGMP-dependent protein kinase I supports an age- and protein synthesis-dependent component of long-term ...
Guanylyl cyclase The concept of second messenger molecules in hormone signal transduction was developed in the 1950s by Earl W ... Kots AY, Martin E, Sharina IG, Murad F. A short history of cGMP, guanylyl cyclases, and cGMP-dependent protein kinases. In: ... Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev. 2000;52:375-413.PubMedGoogle Scholar ... For cyclic purine monophosphates these are adenylate and guanylate cyclases and specific forms of... ...
... the molecular mechanisms behind these GBP-dependent effects are still unknown. Furthermore, no plasma membrane receptors for ... the molecular mechanisms behind these GBP-dependent effects are still unknown. Furthermore, no plasma membrane receptors for ... such as the stimulation of soluble guanylate cyclase and the increase of intracellular cyclic GMP (cGMP; Bau et al., 2005). GUO ... Several effects of GUO are dependent on cell signaling pathways downstream of receptors (e.g., cAMP/Protein Kinase A (PKA), ...
The ability of dopamine to suppress I gamma was blocked by introducing an inhibitor of the cyclic AMP-dependent protein kinase ... an agent which activates guanylate cyclase and increases the intracellular cyclic GMP concentration. The effect of ... Thus, the action of dopamine is mediated by a pathway that includes the activation of a cyclic AMP-dependent kinase. 6. I gamma ... Thus, nitroprusside suppresses I gamma through a pathway that does not include the activation of a cyclic AMP-dependent kinase ...
Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods. Kawamura, S., Murakami, M. ... Localization of guanylate cyclase-activating protein 2 in mammalian retinas. Otto-Bruc, A., Fariss, R.N., Haeseleer, F., Huang ... Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities. Horner, T.J., Osawa, S ... Injection of GTP-binding protein or cyclic GMP phosphodiesterase hyperpolarizes retinal rods. Clack, J.W., Oakley, B., Stein, P ...
These include cyclic nucleotide-dependent protein kinases *Calcium/calmodulin-dependent protein kinase, and protein kinase C ... Guanylate cyclase which catalyzes the conversion of GMP to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as ... Protein kinase C activity is further increased by calcium which is released by the action of inositol phosphates. ... do not have intrinsic kinase activity, but activate soluble, intracellular kinases such as the Jak kinases. ...
Cyclic-GMP-dependent protein kinase in smooth muscle and neutrophils. Adv Second Messenger Phosphoprot Res. 1993;28:121-132. ... Murad F, Waldman S, Molina C, Bennett B, Leitman D. Regulation and role of guanylate cyclase-cyclic GMP in vascular relaxation ... 1 Cyclic GMP in turn activates cGMP-dependent protein kinase types I and II (cGK-I and -II) of which cGK-I is highly expressed ... Endogenous expression of type II cGMP-dependent protein kinase mRNA and protein in rat intestine. Implications for cystic ...
IntracellularGuanosine monophosphatePathwayEnzymesSignal TransductionPhosphodiesteraseNucleotidesInhibitorsProduction of cyclicMetabolismExtracellular signalSecond messenger cyclicConverts GTP to cGMPSynthesisNucleotide-dependentReceptor tyrosiDownstreamMolecularCyclin-dependParticulateSerineAdenylate and guanylate cyclasesActivatorsStimulatesNatriuretic peptideRegulationActivates solublePhosphorylateCalciumSubunitAdenylyl and guanylyl cyclasesVitroCGMP levels
- It is currently accepted that many effects of these endogenous signaling molecules are mediated via stimulation of guanylyl cyclases and intracellular production of the second messenger cGMP. (ahajournals.org)
- Although it is generally accepted that many NO effects are mediated via elevation of intracellular cGMP, one should keep in mind that NO can exert effects independent of cGMP production, for instance via modification of cellular proteins by S-nitrosylation of cysteine residues. (ahajournals.org)
- The concept of second messenger molecules in hormone signal transduction was developed in the 1950s by Earl W. Sutherland describing the cyclic nucleotide adenosine 3′, 5′-cyclic monophosphate (cAMP) as an intracellular messenger molecule. (springer.com)
- The main features of this concept are the binding of a hormone to the extracellular site of a transmembrane receptor protein which triggers an intracellular response mediated by a second messenger molecule (e.g., cAMP). (springer.com)
- Guanine-based purines (GBPs), including the nucleotides guanosine 5′-triphosphate (GTP), guanosine 5′-diphosphate (GDP) and guanosine 5′-monophosphate (GMP), the nucleoside guanosine (GUO) and the nucleobase guanine (GUA) have been traditionally characterized as modulators of intracellular processes, especially considering their role in G protein dependent signal transduction. (frontiersin.org)
- 6. I gamma was suppressed by nitroprusside, an agent which activates guanylate cyclase and increases the intracellular cyclic GMP concentration. (nih.gov)
- 2 3 4 cGK-I has mediated NO/cGMP-caused vasorelaxation, which involves phosphorylation of proteins that affect myosin light chains and intracellular Ca 2+ levels. (ahajournals.org)
- Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. (wikipedia.org)
- Cyclic nucleotides are ubiquitous intracellular messengers. (biomedcentral.com)
- By so doing, the contributors present the role of cyclic nucleotides in relationship to other intracellular regulators. (springer.com)
- The second section is concerned with the biochemistry of protein phosphorylation, a process which appears to be one of the most important mechanisms for the intracellular expression of cyclic nucleotide action in eukaryotic cells. (springer.com)
- domain of its receptor prospects to intracellular activation from the guanylate cyclase domain from the receptor string, and synthesis of the cyclic GMP for activating the cAMP-dependent proteins kinase environment . (perlierusa.com)
- The pathway of stimulated secretion appeared to involve generation of intracellular nitric oxide (NO), activation of soluble guanylate cyclase (GC-S), production of cyclic guanosine monophosphate (cGMP), and activation of cGMP-dependent protein kinase (PKG). (duke.edu)
- NO, by activating soluble guanylyl cyclase, and CNP, by stimulating membrane-bound guanylyl cyclase, cause intracellular increases of cGMP, activating cGMP-dependent protein kinases (PKGs). (jneurosci.org)
- The intracellular domain of the receptor then binds to an intracellular heterotrimeric G protein (since it binds GDP/GTP) in the cell. (tripod.com)
- The intracellular levels of cAMP that enhance hyperalgesia are controlled by the PDE4 isoform and appear to result in the activation of protein kinase A. The balance between the intracellular levels of cAMP and cGMP may be fundamental in the control of pain in response to inflammatory mediators. (ijps.ir)
- These kinases phosphorylate downstream target proteins which mediate cGMP effects, e.g., by decreasing the intracellular calcium concentration. (springer.com)
- When a GPCR is activated by its extracellular ligand, a conformational change is induced in the receptor that is transmitted to an attached intracellular heterotrimeric G protein complex. (wikipedia.org)
- An increased level of intracellular cGMP activates three different targets: cGMP-dependent protein kinases (PKGs), cGMP-dependent. (springer.com)
- The study also aimed to determine whether the altered NO bioavailability that is characteristic of SCD may cause changes in the intracellular levels of NO metabolites and the principal NO second messenger, cyclic guanosine monophosphate (cGMP, produced by the activation of the guanylate cyclase enzyme). (haematologica.org)
- Nitric oxide binds to its intracellular receptor soluble guanylyl cyclase (sGP) and increases cGMP levels. (statpearls.com)
- PSKR belongs to a family of NCs that contains the GC catalytic center embedded within the intracellular kinase domain of leucine rich repeat receptor-like molecules and in in vitro experiments we have demonstrated that both the kinase and the GC domain have catalytic activity. (biomedcentral.com)
- cGMP acts as an intracellular messenger, activating cGMP-dependent kinases and regulating cGMP-sensitive ion channels. (ebi.ac.uk)
- The effect of pH on cerebral vascular tone is mediated by nitric oxide (NO), prostanoids, cyclic nucleotides, potassium channels, and intracellular calcium. (asahq.org)
- Once activated to NO, it activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. (drugbank.ca)
- In addition to GPCRs, a unique family of receptors known as membrane guanylyl cyclases (GCs) can be activated by neuropeptides such as natriuretic peptides to catalyze the intracellular production of cyclic guanosine monophosphate (cGMP) ( 2 , 3 ). (pnas.org)
- He goes on to describe how new molecular biological and biochemical approaches have facilitated a characterization of soluble guanylate cyclase and how this enzyme has acquired a profound physiological significance, and much research attention, as the intracellular 'receptor' for nitric oxide. (embl.de)
- In this review, the role of soluble (nitric oxide (NO)-activated) and membrane-bound, natriuretic peptide (NP)-activated guanylate cyclases that generate the secondary signaling molecule cyclic guanosine monophosphate (cGMP) in the regulation of IOP and in the pathophysiology of POAG will be discussed. (frontiersin.org)
- A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. (patents.com)
- This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. (springer.com)
- The compounds are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. (patentsencyclopedia.com)
- Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). (wikipedia.org)
- Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. (springer.com)
- The soluble guanylate cyclase (s GC) is a key signal transduction enzyme in the nitric oxide (NO) -sGC-cyclic guanosine monophosphate (cGMP) pathway, which can be activated by NO and thus catalyzes the conversion of guanosine triphosphate (GTP) into the c GMP. (bvsalud.org)
- Cyclic guanosine monophosphate (cGMP) is an important secondary messenger synthesized by guanylate cyclases. (reactome.org)
- 3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) is a potential anticancer drug that may activate soluble guanylyl cyclase (sGC) and increase the level of cyclic guanosine monophosphate (cGMP). (biomedcentral.com)
- One such messenger, 3',5'-cyclic guanosine monophosphate (cGMP), has been shown to play a key role in many physiological responses in plants. (biomedcentral.com)
- The heart peptide hormone atrial natriuretic peptide (ANP) regulates blood pressure by stimulating guanylyl cyclase-A to produce cyclic guanosine monophosphate (cGMP). (pnas.org)
- The adenylyl and guanylyl cyclases catalyze the formation of 3', 5'-cyclic adenosine or guanosine monophosphate from the corresponding nucleoside 5'-triphosphate. (embl.de)
- The pathway involving the cyclic guanosine-3′,5′-monophosphate (cGMP) may provide a unique signaling mechanism in regulating axon branching. (jneurosci.org)
- Thus, the action of dopamine is mediated by a pathway that includes the activation of a cyclic AMP-dependent kinase. (nih.gov)
- Thus, nitroprusside suppresses I gamma through a pathway that does not include the activation of a cyclic AMP-dependent kinase. (nih.gov)
- The nitric oxide -induced decreases in cell volume were mimicked by 8-Br-cGMP and abolished by the protein kinase G inhibitor, (RP)-8-Br-PET-cGMP-S suggesting the involvement cGMP and protein kinase G pathway. (ufl.edu)
- Abstract -Studies with cGMP-dependent protein kinase I (cGK-I)-deficient human cells and mice demonstrated that cGK-I ablation completely disrupts the NO/cGMP pathway in vascular tissue, which indicates a key role of this protein kinase as a mediator of the NO/cGMP action. (ahajournals.org)
- This YC-1-induced antiproliferation effect in HUVEC is via a cyclic GMP-independent pathway. (elsevier.com)
- An analog of a dipeptide-like structure of FK506 increases glial cell line-derived neurotrophic factor expression through cAMP response element-binding protein activated by heat shock protein 90/Akt signaling pathway. (semanticscholar.org)
- In the field of molecular biology , the cAMP-dependent pathway , also known as the adenylyl cyclase pathway , is a G protein-coupled receptor -triggered signaling cascade used in cell communication . (wikipedia.org)
- In a cAMP-dependent pathway, the activated G s alpha subunit binds to and activates an enzyme called adenylyl cyclase , which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). (wikipedia.org)
- Specificity of signaling between a GPCR and its ultimate molecular target through a cAMP-dependent pathway may be achieved through formation of a multiprotein complex that includes the GPCR, adenylyl cyclase, and the effector protein. (wikipedia.org)
- cAMP-dependent pathway is necessary for many living organisms and life processes. (wikipedia.org)
- If cAMP-dependent pathway is not controlled, it can ultimately lead to hyper-proliferation, which may contribute to the development and/or progression of cancer . (wikipedia.org)
- This leads to the activation of the cAMP-dependent pathway. (wikipedia.org)
- This pathway can also be activated downstream by directly activating adenylyl cyclase or PKA. (wikipedia.org)
- Western blot-validated results indicated that the core protein network modulated by WGE administration was closely associated with down-regulation of the Slit-Robo pathway, which modulates neuronal cytoskeletal remodeling processes. (jove.com)
- In further studies of this pathway, we have examined the role of MAP kinase pathways in neuronal nitric oxide synthase (nNOS) induction during the differentiation of PC12 cells. (umassmed.edu)
- Two separate protein pathways, both triggered by calcium influx contribute to contraction, a calmodulin driven kinase pathway, and a caldesmon driven pathway. (reactome.org)
- Agents that stimulate the nitric oxide/cGMP-dependent pathway may have beneficial effects on leukocyte function if used in these subjects. (haematologica.org)
- 10 While it has been proposed that HU induces HbF production via tyrosyl radical activation on ribonucleotide reductase, 11 there is evidence to suggest that HU may induce γ-globin gene expression in erythroleukemic cells and primary human erythroblasts via a NO-guanylate cyclase dependent pathway. (haematologica.org)
- Hormones that use the guanylyl cyclase signaling pathway include atrial natriuretic peptide (ANP) and nitric oxide (endothelium-derived relaxing factor, or EDRF). (statpearls.com)
- In this review Adrian Hobbs outlines some of the reasons why the soluble guanylate cyclase-cGMP pathway has remained outside the signalling spotlight for much of the past 30 years. (embl.de)
- Classification and framework of RTKs Proteins kinases are fundamental enzymes in the rules of various mobile procedures that catalyse the transfer of the phosphate group from ATP to a hydroxyl band of a serine or a threonine. (perlierusa.com)
- ncNOS and ecNOS are calcium dependent and low output enzymes associated with NO production in the picomolar range, whereas iNOS is a calcium independent and high output enzyme associated with NO production in the nanomolar (nmol) range. (bmj.com)
- Kinases are a class of enzymes which use ATP to phosphorylate molecules within the cell. (tripod.com)
- Protein kinase - enzymes that use ATP to phosphorylate proteins within the cell. (tripod.com)
- Secondly, the soluble guanylate cyclase (sGC), a major target of NO action, and cGMP-regulated enzymes like cGMP-dependent protein kinase and cyclic nucleotide gated channels are described. (nih.gov)
- Substantial attenuation in current is seen in the presence of the base-flipping enzymes HhaI methylase and uracil DNA glycosylase, as well as with TATA-binding protein. (jove.com)
- Soluble guanylyl cyclases (SGCs) are dimeric enzymes that transduce signals downstream of nitric oxide (NO) in animals. (biomedcentral.com)
- Nitric oxide, bicarbonate, and natriuretic peptides such as ANP and BNP, activate the guanylyl cyclase enzymes, which then form the cyclic GMP. (statpearls.com)
- Other activators of guanylyl cyclase enzymes include uroguanylin, guanylin, and guanylyl cyclase activating proteins. (statpearls.com)
- However, in higher plants, guanylyl cyclases (GCs), enzymes that generate cGMP from guanosine-5'-triphosphate (GTP) have remained elusive until recently. (biomedcentral.com)
- If it turns out that plants do harbor a large number of functional GC domains as part of multi-domain enzymes, then major new insights will be gained into the complex signal transduction pathways that link cGMP to fundamental processes such as ion transport and homeostasis, biotic and abiotic stress responses as well as cGMP-dependent responses to hormones. (biomedcentral.com)
- Guanylyl cyclases, a growing family of signal-transducing enzymes. (ebi.ac.uk)
- In most tissues, CBS and CSE, which are responsible for catalyzing the production of H 2 S, are both pyridoxal-5-phosphate-dependent enzymes that utilize cysteine and homocysteine as substrates to liberate ammonium, pyruvate, and H 2 S [ 6 ]. (hindawi.com)
- Membrane guanylate cyclase is a beautiful signal transduction machine: overview. (springer.com)
- Our results demonstrate that NO inhibits Cl-/OH- exchange activity in Caco-2 cells via cGMP-dependent protein kinases G (PKG) and C (PKC) signal-transduction pathways. (biomedsearch.com)
- Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. (plos.org)
- NO stimulates signal transduction pathways through protein kinases, cytosolic Ca 2+ mobilization and protein modification (i.e. nitrosylation and nitration). (wiley.com)
- M 3 mAChRs trigger similar signal transduction pathways that involve the heterotrimeric G protein Gq-mediated activation of phospholipase C (PLC) - β , which results in the generation of inositol 1,4,5-trisphosphate (IP 3 ) and 1,2-diacylglycerol (DAG). (aspetjournals.org)
- Subsequently, elevated cGMP activates cGMP-dependent protein kinase (PKG) and downstream signal transduction to regulate many cellular responses [ 11 ]. (biomedcentral.com)
- Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. (diva-portal.org)
- Useful of course for in vitro kinase and phosphodiesterase mapping studies! (biolog.de)
- Here we show that in platelets and aortic tissue, NO led to a biphasic response characterized by a tremendous increase in cGMP (up to 100-fold) in less than 30 s and a rapid decline, reflecting the tightly controlled balance of guanylyl cyclase and phosphodiesterase activities. (rupress.org)
- The activation of soluble guanylyl cyclase leads to increased cGMP concentration, and this leads to soluble guanylyl cyclase transmitting a NO signal to downstream proteins in the signaling cascade: cGMP dependent protein kinase, cGMP gated cation channels, and cGMP regulated phosphodiesterase. (statpearls.com)
- Pharmacological applications reveal that this blockade is mediated by phosphodiesterase 2A (PDE2A) but not by cGMP-stimulated protein kinase-G or cGMP-sensitive cyclic nucleotide-gated channels. (pnas.org)
- Until recently, the roles of cyclic nucleotides in plant cells have proven difficult to uncover. (biomedcentral.com)
- With an understanding of the protein domains which can bind cyclic nucleotides (CNB and GAF domains) we scanned the completed genomes of the higher plants Arabidopsis thaliana (mustard weed) and Oryza sativa (rice) for the effectors of these signalling molecules. (biomedcentral.com)
- The ubiquitous presence of cyclic nucleotides may be due to several characteristics which make it an ideal second messenger. (biomedcentral.com)
- Cyclic nucleotides are derived in a energetically favourable reaction from common metabolites (ATP and GTP), and can be broken down into non-toxic products (inorganic phosphate and AMP/GMP). (biomedcentral.com)
- In plants, cyclic nucleotides have endured a checkered research history fraught with complications and setbacks. (biomedcentral.com)
- Cyclic nucleotides are able to bind to two distinct protein domains, CNB domains and GAF domains. (biomedcentral.com)
- Therefore, GAF and CNB domains have evolved independently to bind cyclic nucleotides. (biomedcentral.com)
- In order to further explore the roles of cyclic nucleotides in plants, we performed a bioinformatics based analysis of the completed Arabidopsis thaliana and Orzya sativa genomes [ 21 - 23 ] in order to elucidate the potential targets of cyclic nucleotides in plants. (biomedcentral.com)
- The purpose of the present volume, the first of two on the pharmacology, biochemistry, and physiology of cyclic nucleotides, is to provide a comprehensive and up-to-date anthology on the nature and role of these important chemical regulators. (springer.com)
- The hydrolysis of the cyclic nucleotides cAMP and cGMP to their corresponding inactive 5'-monophosphate counterparts is catalyzed by PDEs as a superfamily . (ijps.ir)
- Most of these studies focus on the exogenous addition of stimuli that modulate the levels of these cyclic nucleotides. (ijps.ir)
- However, a considerable number of studies have investigated the importance of the balance of these cyclic nucleotides in the genesis of inflammatory hyperalgesia [5- (ijps.ir)
- Protein complexes may have other associated non-protein prosthetic groups, such as nucleotides, metal ions or other small molecules. (geneontology.org)
- Therefore, our project aims at differentiating between first- and second messenger functions of cGMP and the other cyclic nucleotides (cNMPs) cAMP, cUMP and cCMP in various cellular systems and functional readouts. (biomedcentral.com)
- None of the unmodified cyclic nucleotides (cAMP, cGMP, cUMP, cCMP) caused apoptosis in S49 wt or S49 kin - cells, and the cell-permeable AMs of cAMP, cGMP and cUMP were not active either. (biomedcentral.com)
- Moreover, the surprisingly strong pro-apoptotic effect of cCMP-AM on S49 cells warrants similar studies with cyclic pyrimidine nucleotides. (biomedcentral.com)
- Inhibitors and activators were used to characterize the involvement of nitric oxide, soluble guanylate cyclase, cyclic GMP, protein kinase G and BKCa channel. (ufl.edu)
- We further show that LTD induced by low-frequency stimulation in the absence of SNAP also is blocked by KT5823 or Rp-8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate (10 microM), cyclic guanosine 3',5' monophosphate-dependent protein kinase (PKG) inhibitors with different mechanisms of action. (ox.ac.uk)
- Eukaryotic cell cycle progression is regulated by cyclin-dependent kinases (CDKs), which phosphorylate and dephosphorylate binding proteins such as cyclins and CDK inhibitors (CKIs) ( Morgan, 1995 ). (aspetjournals.org)
- Drug resistance mutations in response to HIV-1 protease inhibitors are selected not only in the drug target but elsewhere in the viral genome, especially at the protease cleavage sites in the precursor protein Gag. (jove.com)
- A novel mechanism for exisulind to induce apoptosis is studied involving sustained increases in cGMP levels and cGMP-dependent protein kinase (PKG) induction not found with selective PDE5 or most other PDE inhibitors. (aacrjournals.org)
- This process has an additional requirement for release of Ca2+ from ryanodine-sensitive stores, perhaps dependent on the second-messenger cyclic ADP ribose. (ox.ac.uk)
- Guanylyl cyclase (GC) catalyzes the formation of the second messenger cyclic GMP (cGMP) from GTP and exists in both the soluble and particulate fractions. (merckmillipore.com)
- The receptor has intrinsic guanylate cyclase activity, and the guanylyl cyclase converts GTP to cGMP. (statpearls.com)
- this converts GTP to cGMP, which acts as a second messenger to activate protein kinase G. Activation of protein kinase G causes smooth muscle relaxation and vasodilation. (statpearls.com)
- Guanylate cyclase (GC) catalyzes cGMP synthesis. (wikipedia.org)
- Furthermore, the recent identification and cloning of adenylate and guanylate cyclases in plants [ 7 , 10 ] may eventually give clues as to what signals the synthesis and degradation of these molecules in plants. (biomedcentral.com)
- YC-1 at a range of concentrations (5-50μM) inhibited DNA synthesis and decreased cell number in cultured HUVEC in a dose- and time-dependent manner. (elsevier.com)
- ERK1/2 then activates MNK1 / eIF4E , and thereby induces protein synthesis [ 11 ], [ 13 ]. (bio-rad.com)
- Guanylyl cyclase catalyzes the synthesis of cGMP from GTP. (statpearls.com)
- In all characterised eukaryote guanylyl- and adenylyl cyclases, cyclic nucleotide synthesis is carried out by the conserved class III cyclase domain. (ebi.ac.uk)
- Cyclic GMP has been proposed to regulate axonal development, but the molecular and cellular mechanisms underlying the formation of axon branches are not well understood. (jneurosci.org)
- GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. (frontiersin.org)
- B) Co-transfection of PKG1β and HIV-1 infectious molecular clone, pNL4-3, resulted in dose dependent increase in viral protein expression. (biomedcentral.com)
- Viral proteins expressed from the HIV-1 molecular clone were then measured. (biomedcentral.com)
- UniProtKB-GOA are currently considering using the protein complex identifier as a principal annotation object in GO annotations (column 2) that refer to the biological processes or molecular functions carried out specifically by a complex. (geneontology.org)
- Inhibiting the main molecular target of NO, soluble guanylate cyclase, with ODQ reduced the cycle frequency of the rhythm, suggesting that NO mediated its effects via sGC and cyclic GMP. (biologists.org)
- Of note, YC-1 induced a dramatic increase in the expression of cyclin-dependent kinase (CDK)-inhibitory protein, p21 CIP1/WAP1 , and a modest increase in p27 KIP1 . (aspetjournals.org)
- Western blot analysis demonstrated that YC-1 (5-50μM) increased the levels of cyclin-dependent kinase (CDK)-inhibitory proteins (CKIs), p21 and p27, but did not induce any significant changes of cyclins and CDKs. (elsevier.com)
- Their binding to soluble guanylyl cyclase (sGC) and particulate guanylyl cyclase (pGC), respectively, increases the formation of cGMP which is a unique second messenger. (springer.com)
- Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide-cyclic GMP signalling. (springer.com)
- cGMP-dependent protein kinase or Protein Kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP . (wikidoc.org)
- PKG are serine/threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organism Paramecium to humans. (wikidoc.org)
- Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. (plos.org)
- The Chemistry and Biology of Soluble Guanylate Cyclase Stimulators and Activators, Angewandte Chemie--International Edition, 2013, pp. 9442-9462, Vol. 52 Issue 36. (patents.com)
- The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. (patentsencyclopedia.com)
- These data suggest that activators of neutrophil degranulation mediate this response through a cGMP- dependent protein kinase mechanism. (elsevier.com)
- Martel G, Hamet P, Trembly J. Central role of guanylyl cyclase in natriuretic peptide signaling in hypertension and metabolic syndrome. (springer.com)
- A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. (springer.com)
- Guanylyl cyclase/atrial natriuretic peptide receptor-A: role in the pathophysiology of cardiovascular regulation. (springer.com)
- It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. (springer.com)
- cGMP is involved in the regulation of some protein-dependent kinases. (wikipedia.org)
- Wyatt, TA , Lincoln, TM & Pryzwansky, KB 1993, ' Regulation of human neutrophil degranulation by LY-83583 and L-arginine: Role of cGMP-dependent protein kinase ', American Journal of Physiology - Cell Physiology , vol. 265, no. 1 34-1, pp. (elsevier.com)
- Guanylyl cyclase structure, function and regulation. (springer.com)
- Structure, mechanism, and regulation of mammalian adenylyl cyclase. (embl.de)
- NO production by eNOS is dependent on calcium-calmodulin and other cofactors. (wikipedia.org)
- Given the increased rod calcium levels present in the rd1 mutation, calcium-evoked overactivation of this kinase may be an early and long sought for step in events leading to photoreceptor degeneration in the rd1 mouse. (mcponline.org)
- A prominent exposed patch of hydrophobic residues formed by EF-1 and EF-2 (Leu24, Trp27, Phe31, Phe45, Phe48, Phe49, Tyr81, Val82, Leu85, and Leu89) may serve as a target-binding site for the transmission of calcium signals to guanylyl cyclase. (stanford.edu)
- CNB domains were first identified in the regulatory subunit of mammalian cAMP-dependent protein kinase (RI and RII). (biomedcentral.com)
- The G s alpha subunit of the stimulated G protein complex exchanges GDP for GTP and is released from the complex. (wikipedia.org)
- The G s alpha subunit, in turn, activates adenylyl cyclase, which quickly converts ATP into cAMP. (wikipedia.org)
- Soluble guanylate cyclase is a heterodimeric protein with an alpha and beta subunit. (statpearls.com)
- Recent in vitro and in vivo evidence identifies cGMP-dependent protein kinases (cGKs) as major mediators of cGMP signaling in the cardiovascular system. (ahajournals.org)
- The EC50 value for this in vitro response is found to be 27 microM and the c-GMP level is maximally 9-fold elevated by 100 microM histamine. (nih.gov)
- We used the stable NO donor S-nitroso-N-acetylpenicillamine (SNAP) to study the NO-dependent form of LTD at Schaffer collateral-CA1 synapses in vitro. (ox.ac.uk)
- The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. (diva-portal.org)
- Degranulation, elevation of cGMP levels, and targeting of G-kinase were also dependent on the concentration of A-23187 or FMLP. (elsevier.com)