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)
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
Agents that inhibit PROTEIN KINASES.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A 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.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A 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.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
The rate dynamics in chemical or physical systems.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A species of ciliate protozoa. It is used in biomedical research.
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.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Established cell cultures that have the potential to propagate indefinitely.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
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.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A 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.
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)
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
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.
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.
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.
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)
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.
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
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.
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.
An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
A 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.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
A 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.
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.
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.
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Proteins prepared by recombinant DNA technology.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
The sum of the weight of all the atoms in a molecule.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
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.
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.
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.
The nonstriated involuntary muscle tissue of blood vessels.
A group of compounds that contain the structure SO2NH2.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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).
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A 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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
RNA 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.
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.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
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.
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.
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.
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.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
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.
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.
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 KINASES
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A 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.
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.
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.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
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.
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.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A 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.
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.
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.
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.
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.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
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.
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).
A cell line derived from cultured tumor cells.
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.
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.
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)
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.
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A group of phenyl benzopyrans named for having structures like FLAVONES.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
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.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
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.
A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
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).
Compounds or factors that act on a specific enzyme to increase its activity.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
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.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The phosphoric acid ester of serine.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
That phase of a muscle twitch during which a muscle returns to a resting position.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.

Nitric oxide modulates endothelin 1-induced Ca2+ mobilization and cytoskeletal F-actin filaments in human cerebromicrovascular endothelial cells. (1/1035)

A functional interrelation between nitric oxide (NO), the endothelial-derived vasodilating factor, and endothelin 1 (ET-1), the potent vasoconstrictive peptide, was investigated in microvascular endothelium of human brain. Nor-1 dose-dependently decreased the ET-1-stimulated mobilization of Ca2+. This response was mimicked with cGMP and abrogated by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase G. These findings indicate that NO and ET-1 interactions involved in modulation of intracellular Ca2+ are mediated by cGMP/protein kinase G. In addition, Nor-1-mediated effects were associated with rearrangements of cytoskeleton F-actin filaments. The results suggest mechanisms by which NO-ET-1 interactions may contribute to regulation of microvascular function.  (+info)

Molecular identification of human G-substrate, a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells. (2/1035)

G-substrate, an endogenous substrate for cGMP-dependent protein kinase, exists almost exclusively in cerebellar Purkinje cells, where it is possibly involved in the induction of long-term depression. A G-substrate cDNA was identified by screening expressed sequence tag databases from a human brain library. The deduced amino acid sequence of human G-substrate contained two putative phosphorylation sites (Thr-68 and Thr-119) with amino acid sequences [KPRRKDT(p)PALH] that were identical to those reported for rabbit G-substrate. G-substrate mRNA was expressed almost exclusively in the cerebellum as a single transcript. The human G-substrate gene was mapped to human chromosome 7p15 by radiation hybrid panel analysis. In vitro translation products of the cDNA showed an apparent molecular mass of 24 kDa on SDS/PAGE which was close to that of purified rabbit G-substrate (23 kDa). Bacterially expressed human G-substrate is a heat-stable and acid-soluble protein that cross-reacts with antibodies raised against rabbit G-substrate. Recombinant human G-substrate was phosphorylated efficiently by cGMP-dependent protein kinase exclusively at Thr residues, and it was recognized by antibodies specific for rabbit phospho-G-substrate. The amino acid sequences surrounding the sites of phosphorylation in G-substrate are related to those around Thr-34 and Thr-35 of the dopamine- and cAMP-regulated phosphoprotein DARPP-32 and inhibitor-1, respectively, two potent inhibitors of protein phosphatase 1. However, purified G-substrate phosphorylated by cGMP-dependent protein kinase inhibited protein phosphatase 2A more effectively than protein phosphatase 1, suggesting a distinct role as a protein phosphatase inhibitor.  (+info)

Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic nucleotide-dependent kinases in vitro and in rat cerebellar slices in situ. (3/1035)

We have examined cyclic nucleotide-regulated phosphorylation of the neuronal type I inositol 1,4,5-trisphosphate (IP3) receptor immunopurified from rat cerebellar membranes in vitro and in rat cerebellar slices in situ. The isolated IP3 receptor protein was phosphorylated by both cAMP- and cGMP-dependent protein kinases on two distinct sites as determined by thermolytic phosphopeptide mapping, phosphopeptide 1, representing Ser-1589, and phosphopeptide 2, representing Ser-1756 in the rat protein (Ferris, C. D., Cameron, A. M., Bredt, D. S., Huganir, R. L., and Snyder, S. H. (1991) Biochem. Biophys. Res. Commun. 175, 192-198). Phosphopeptide maps show that cAMP-dependent protein kinase (PKA) labeled both sites with the same time course and same stoichiometry, whereas cGMP-dependent protein kinase (PKG) phosphorylated Ser-1756 with a higher velocity and a higher stoichiometry than Ser-1589. Synthetic decapeptides corresponding to the two phosphorylation sites (peptide 1, AARRDSVLAA (Ser-1589), and peptide 2, SGRRESLTSF (Ser-1756)) were used to determine kinetic constants for the phosphorylation by PKG and PKA, and the catalytic efficiencies were in agreement with the results obtained by in vitro phosphorylation of the intact protein. In cerebellar slices prelabeled with [32P]orthophosphate, activation of endogenous kinases by incubation in the presence of cAMP/cGMP analogues and specific inhibitors of PKG and PKA induced in both cases a 3-fold increase in phosphorylation of the IP3 receptor. Thermolytic phosphopeptide mapping of in situ labeled IP3 receptor by PKA showed labeling on the same sites (Ser-1589 and Ser-1756) as in vitro. In contrast to the findings in vitro, PKG preferentially phosphorylated Ser-1589 in situ. Because both PKG and the IP3 receptor are specifically enriched in cerebellar Purkinje cells, PKG may be an important IP3 receptor regulator in vivo.  (+info)

Interplay between the NO pathway and elevated [Ca2+]i enhances ciliary activity in rabbit trachea. (4/1035)

1. Average intracellular calcium concentration ([Ca2+]i) and ciliary beat frequency (CBF) were simultaneously measured in rabbit airway ciliated cells in order to elucidate the molecular events that lead to ciliary activation by purinergic stimulation. 2. Extracellular ATP and extracellular UTP caused a rapid increase in both [Ca2+]i and CBF. These effects were practically abolished by a phospholipase C inhibitor (U-73122) or by suramin. 3. The effects of extracellular ATP were not altered: when protein kinase C (PKC) was inhibited by either GF 109203X or chelerythrine chloride, or when protein kinase A (PKA) was inhibited by RP-adenosine 3', 5'-cyclic monophosphothioate triethylamine (Rp-cAMPS). 4. Activation of PKC by phorbol 12-myristate, 13-acetate (TPA) had little effect on CBF or on [Ca2+]i, while activation of PKA by forskolin or by dibutyryl-cAMP led to a small rise in CBF without affecting [Ca2+]i. 5. Direct activation of protein kinase G (PKG) with dibutyryl-cGMP had a negligible effect on CBF when [Ca2+]i was at basal level. However, dibutyryl-cGMP strongly elevated CBF when [Ca2+]i was elevated either by extracellular ATP or by ionomycin. 6. The findings suggest that the initial rise in [Ca2+]i induced by extracellular ATP activates the NO pathway, thus leading to PKG activation. In the continuous presence of elevated [Ca2+]i the stimulated PKG then induces a robust enhancement in CBF. In parallel, activated PKG plays a central role in Ca2+ influx via a still unidentified mechanism, and thus, through positive feedback, maintains CBF close to its maximal level in the continuous presence of ATP.  (+info)

Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells. (5/1035)

The present study investigates the potential role of the Ca2+-calmodulin-dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell videoimaging. Vinpocetine (2.5-50 microM), a selective inhibitor of type I PDE, induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations in these pituitary cells, and at the same time produced an increase of the intracellular cGMP content. The cell permeable cGMP analog N2,2'-O-dibutyryl-cGMP (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823 (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor. Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage-sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic cGMP levels. Collectively, the results of the present study suggest that spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of type I PDE-cGMP-PKG pathway.  (+info)

Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene transcription. (6/1035)

The ability of cGMP-dependent protein kinases (cGKs) to activate cAMP response element (CRE)-dependent gene transcription was compared with that of cAMP-dependent protein kinases (cAKs). Although both the type Ibeta cGMP-dependent protein kinase (cGKIbeta) and the type II cAMP-dependent protein kinase (cAKII) phosphorylated the cytoplasmic substrate VASP (vasodilator- and A kinase-stimulated phosphoprotein) to a similar extent, cyclic nucleotide regulation of CRE-dependent transcription was at least 10-fold higher in cAKII-transfected cells than in cGKIbeta-transfected cells. Overexpression of each kinase in mammalian cells resulted in a cytoplasmic localization of the unactivated enzyme. As reported previously, the catalytic (C) subunit of cAKII translocated to the nucleus following activation by 8-bromo-cyclic AMP. However, cGKIbeta did not translocate to the nucleus upon activation by 8-bromo-cyclic GMP. Replacement of an autophosphorylated serine (Ser79) of cGKIbeta with an aspartic acid resulted in a mutant kinase with constitutive kinase activity in vitro and in vivo. The cGKIbetaS79D mutant localized to the cytoplasm and was only a weak activator of CRE-dependent gene transcription. However, an amino-terminal deletion mutant of cGKIbeta was found in the nucleus as well as the cytoplasm and was a strong activator of CRE-dependent gene transcription. These data suggest that the inability of cGKs to translocate to the nucleus is responsible for the differential ability of cAKs and cGKs to activate CRE-dependent gene transcription and that nuclear redistribution of cGKs is not required for NO/cGMP regulation of gene transcription.  (+info)

A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. (7/1035)

High-frequency stimulation (HFS) of corticostriatal glutamatergic fibers induces long-term depression (LTD) of excitatory synaptic potentials recorded from striatal spiny neurons. This form of LTD can be mimicked by zaprinast, a selective inhibitor of cGMP phosphodiesterases (PDEs). Biochemical analysis shows that most of the striatal cGMP PDE activity is calmodulin-dependent and inhibited by zaprinast. The zaprinast-induced LTD occludes further depression by tetanic stimulation and vice versa. Both forms of synaptic plasticity are blocked by intracellular 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, indicating that an increased cGMP production in the spiny neuron is a key step. Accordingly, intracellular cGMP, activating protein kinase G (PKG), also induces LTD. Nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) block LTD induced by either HFS or zaprinast, but not that induced by cGMP. LTD is also induced by the NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine. SNAP-induced LTD occludes further depression by HFS or zaprinast, and it is blocked by intracellular ODQ but not by L-NAME. Intracellular application of PKG inhibitors blocks LTD induced by HFS, zaprinast, and SNAP. Electron microscopy immunocytochemistry shows the presence of NOS-positive terminals of striatal interneurons forming synaptic contacts with dendrites of spiny neurons. These findings represent the first demonstration that the NO/cGMP pathway exerts a feed-forward control on the corticostriatal synaptic plasticity.  (+info)

Nitric oxide regulation of gene transcription via soluble guanylate cyclase and type I cGMP-dependent protein kinase. (8/1035)

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

This study shows that in vitro exposure to high glucose (i.e., 25 mmol/L) of platelets from healthy subjects reduces the antiaggregating action of aspirin, an effect blunted by the antioxidant agent amifostine. It also shows that high glucose does not affect the ability of aspirin to inhibit thromboxane synthesis but impairs the ability of aspirin to activate the NO/cGMP/PKG pathway. Furthermore, it demonstrates that high glucose per se does not influence platelet aggregation in response to agonists, thromboxane synthesis, and the NO/cGMP/PKG pathway.. Thus, high glucose reduces the antiaggregating properties of aspirin only at very high concentrations; the extent of inhibition, although significant, is modest. In our experimental conditions, we did not observe the dramatic dose-dependent inhibition of platelet sensitivity to aspirin described by other authors (17,19).. Is it possible to translate results obtained in vitro to in vivo conditions? It is interesting to observe that the lack of ...
The expression and phosphorylation state of VASP was investigated in neutrophils during cell adherence. Adhesion is an essential process for neutrophil migration from the peripheral blood to sites of inflammation. During the process of adhesion, neutrophils adhere and spread without any clear stopping point between these two processes. Therefore, it was important to determine whether VASP was phosphorylated in response to signals involved in adhesion and/or spreading. In this report, we demonstrate that VASP is a target for cGK regulation of neutrophil spreading. We showed that VASP was in its dephosphorylated form in retracted round neutrophils and was rapidly phosphorylated by cGK at the onset of cell spreading. Both adherence and the onset of cell spreading induced significant elevations of cGMP in neutrophils. When neutrophils were incubated with 8-Br-cGMP, a direct activator of cGK, cells became more polarized in suspension, and spread more rapidly during adhesion. Our observations that ...
TY - JOUR. T1 - Phosphorylation of tyrosine hydroxylase by cyclic GMP - Dependent protein kinase. AU - Roskoski, R.. AU - Vulliet, Philip R. AU - Glass, D. B.. PY - 1987. Y1 - 1987. N2 - Tyrosine hydroxylase purified from rat pheochromycytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. The extent of activation was correlated with the degree of phosphate incorporated into the enzyme. Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP-dependent protein kinases. The enzymes appeared to mediate the phosphorylation of the same residue based on the observation that incorporation was not increased when both enzymes were present. The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following ...
In addition to vasodilation, NO/NP/cGMP signaling is involved in the development of vasculoproliferative disorders, such as restenosis and atherosclerosis. The analysis of transgenic mice showed that NO can both promote58-64 and inhibit65-70 pathological vascular remodeling (see review5). This finding could explain why NO-generating drugs have not been reported to limit the progression of atherosclerosis in humans. The opposing actions of NO might depend on the magnitude and spatiotemporal profile of its production in a specific pathophysiological setting and are likely mediated through different cellular and molecular mechanisms. A key process in vascular remodeling is the phenotypic modulation of vascular SMCs from contractile to proliferating/dedifferentiated cells.71 It has been reported that NO and cGMP can both promote72,73 and inhibit74,75 the proliferation of cultured SMCs (see reviews12,76). The reason for these contradictory findings and their (patho)physiological significance is not ...
Clinical malaria is associated with the proliferation of Plasmodium parasites in human erythrocytes. The coordinated processes of parasite egress from and invasion into erythrocytes are rapid and tightly regulated. We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. Parasites deficient in PfCDPK5 arrested as mature schizonts with intact membranes, despite normal maturation of egress proteases and invasion ligands. Merozoites physically released from stalled schizonts were capable of invading new erythrocytes, separating the pathways of egress and invasion. The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. Thus, PfCDPK5 plays an essential role during the blood stage of malaria replication ...
the objective of this investigation was to study the effect of the presence of red blood cells (RBCs) in the plasma layer adjacent to the arteriole wall on coupled nitric oxide (NO) and oxygen (O2) transport using computer simulations and to compare our model predictions with experimental data from the literature.. NO, produced by endothelial cells lining the vessel wall, diffuses both into the vessel lumen and to surrounding tissues. Most endothelium-derived NO is scavenged by hemoglobin in the RBCs in the bloodstream, and only a portion diffuses abluminally. The portion that diffuses into the vessel wall activates soluble guanylate cyclase (sGC), catalyzing the formation of cyclic 3′,5′-guanosine monophosphate and activating cyclic 3′,5′-guanosine monophosphate-dependent protein kinase. This results in a decrease of Ca2+ inside smooth muscle cells and dephosphorylation of contractile proteins, such as myosin light chain, causing relaxation of vascular smooth muscle (8, 24). Generation ...
Long-term depression (LTD) of synaptic transmission can be induced by several mechanisms, one thought to involve Ca2+-dependent activation of postsynaptic nitric oxide (NO) synthase and subsequent diffusion of NO to the presynaptic terminal. 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. SNAP (100 microM) enhanced the induction of LTD via a cascade that was blocked by the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonopentanoic acid (50 microM), NO guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (10 microM), and the PKG inhibitor KT5823 (1 microM). 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.
Cyclic GMP (cGMP) kinase is intimately involved in the regulation of vascular smooth muscle tone. Its tissue concentration was determined in normotensive and hypertensive rats by use of monospecific anti-cGMP kinase antibodies. Hearts of spontaneously hypertensive rats and renovascular (Goldblatt II) hypertensive rats contained half the concentration of cGMP kinase than those of the respective normotensive animals. The increase in blood pressure and the resulting left ventricular hypertrophy were correlated inversely with the left ventricular cGMP kinase concentration. This decrease was specific for the left ventricle and was not observed in other tissues. In addition, the cardiac concentration of cGMP kinase was unchanged in hyperthyroid animals that had comparable left ventricular hypertrophy and mild hypertension. This suggested that in severe renovascular hypertension the decrease in cardiac cGMP kinase concentration is caused by a relative lack of cardiac vessel growth during the ...
We have discovered that PKG activation by either genetic or pharmacological means was sufficient to destabilize a surrogate misfolded protein (GFPu) substrate of the UPS, whereas PKG inhibition stabilizes the GFPu proteins in cultured cardiomyocytes. Moreover, we have also shown that PKG activation by sildenafil treatment significantly decreases myocardial GFPdgn protein levels but displays no discernible effect on GFPdgn mRNA levels in GFPdgn tg mice. These findings suggest that PKG positively regulates the degradation of a misfolded protein by the UPS. We have further tested this postulate in both cultured cardiomyocytes and intact mice that overexpress CryABR120G, a bona fide misfolded protein known to cause human disease.24 We collected compelling evidence that PKG activation by either genetic or pharmacological methods facilitates whereas PKG inhibition by genetic and pharmacological means decreases the UPS-mediated degradation of CryABR120G in cultured NRVMs.. Sildenafil treatment showed ...
cGMP-dependent protein kinases (PKG) exhibit diverse physiological functions in the mammalian system e.g., in vascular and gastrointestinal smooth muscles, in platelets, in kidney, in bone growth, nociception and in the central nervous system. Furthermore, PKG were found in insects and in the malaria parasite Plasmodium falciparum. Two different genes of PKG exist: a) the PKG-I gene that is expressed as cytosolic PKG-Iα or PKG-Iβ isoform, and b) the PKG-II gene, which expresses the membrane associated PKG-II protein. The enzyme kinetics, the localization and the substrates of these PKG enzymes differ utilizing different physiological functions. Various inhibitors of PKG were developed directed against diverse functional regions of the kinase. These inhibitors of PKG have been used to analyse the specific functions of these enzymes. The review article will summarize these different inhibitors regarding their specificity and their present applications in vitro and in vivo. Furthermore, it will be
Previously, our lab showed that low-level nitric oxide (NO) and downstream activation of the cGMP/protein kinase G (PKG) signaling pathway plays a key role in preventing spontaneous apoptosis and stimulating proliferation in many mammalian cells, including neural cells, vascular smooth muscle cells and certain tumor cells (e.g. human ovarian cancer cells). In cancer cells, PKG is hyper-activated, which may contribute to rapid cell proliferation and resistance to chemotherapy. Recently, our lab found that two mesothelioma cell lines (MSTO-211H and NCI-H2452 cells) and two prostate cancer cell lines (PC-3 and DU145 cells) also show dependence on endogenous NO/cGMP/PKG pathway for promoting proliferation and cell survival (contributing to cisplatin-resistance). Pharmacological blocking of either NO-induced cGMP synthesis (using ODQ) or PKG enzymatic activity (using DT-2) in mesothelioma and prostate cancer cells decreases proliferation rate, increases apoptosis and sensitizes cells to cisplatin. ...
The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling appears to play a key role in inhibiting neuroinflammation and preventing the activation of a proapoptotic pathway, thereby promoting neural cell survival. In addition, evidence indicates that cGMP/protein kinase G (PKG) pathway is involved in the modulation of glial cell activity. Phosphodiesterase 5 (PDE5), which hydrolyzes cGMP in the inactive form, 5ʹGMP, is present throughout the body and brain and has emerged as a potential therapeutic target for diseases related to neuroinflammatory and neurodegenerative processes, since their inhibition leads to accumulation of cGMP. The objective of this chapter is to review current knowledge of NO/cGMP signaling pathways on neuroinflammation and the potential therapeutic use of PDE5 inhibitors (PDE5-Is) in neurological diseases. The extensive, while recent, literature on the effects of PDE-Is on Alzheimers disease (AD), multiple sclerosis (MS), Parkinsons disease (PD), Huntingtons disease
Protein kinase G (PKG) is activated by nitric oxide (NO)-induced cGMP binding or alternatively by oxidant-induced interprotein disulfide formation. We found preactivation with cGMP attenuated PKG oxidation. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) blockade of cGMP production increased disulfide PKG to 13±2% and 29±4% of total in aorta and mesenteries, respectively. This was potentially anomalous, because we observed 2.7-fold higher NO levels in aorta than mesenteries; consequently, we had anticipated that ODQ would induce more disulfide in the conduit vessel. ODQ also constricted aorta, whereas it had no effect on mesenteries. Thus, mesenteries, but not aorta, can compensate for loss of NO-cGMP by recruiting disulfide activation of PKG. Mechanistically, this is explained by loss of cGMP allowing disulfide formation in response to basal oxidant production. Why aorta treated with ODQ generated less PKG disulfide that is insufficient to induce vasoconstriction was unclear. One potential ...
Genes can affect natural behavioral variation in different ways. Allelic variation causes alternative behavioral phenotypes, whereas changes in gene expression can influence the initiation of behavior at different ages. We show that the age-related transition by honey bees from hive work to foraging is associated with an increase in the expression of the foraging (for) gene, which encodes a guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG). cGMP treatment elevated PKG activity and caused foraging behavior. Previous research showed that allelic differences in PKG expression result in two Drosophila foraging variants. The same gene can thus exert different types of influence on a behavior. ...
Cyclic guanosine 3,5-monophosphate (cGMP)-dependent protein kinase (PKG) activates a signaling pathway that leads to vascular smooth muscle cell relaxation, a process that reduces blood pressure. This enzyme consists of a dimerization domain, autoinhibitory domain, regulatory domain, and catalytic domain1. PKG is activated by cGMP binding to two binding sites of the regulatory domain. In order to study how each of these two binding sites, A and B, contributes to PKG activation, a mutant that knocked out cGMP binding to the B site, PKG Iα E292A, was expressed in Sf9 cells and purified to apparent homogeneity. Despite the presence of this mutation, the affinity for cGMP determined by surface plasmon resonance (SPR) was unchanged. The mutant still displayed cGMP dependent activation. In addition to these cGMP-binding sites, the regulatory domain contains a switch helix motif that provides a place for crosstalk between the PKG protomers2. It is not well known how this motif affects cyclic
Cardiac stress results in several adverse effects, including hypertrophy and pathological remodeling, that lead to heart failure. Activation of the cGMP-dependent kinase PKG1α, which mediates cardiac and vascular function in response to NO and natriuretic peptide signaling, has been shown to suppress detrimental responses to cardiac stress. These beneficial effects have led to the exploration of PKG1α as a potential therapeutic target; however, clinical outcomes have been variable. Taishi Nakamura and colleagues at Johns Hopkins Medical Institutions demonstrate that oxidation of PKG1α in response to cardiac stress contributes to adverse heart remodeling. In patients with ischemic heart failure and rodent heart disease models, PKG1α oxidation was increased compared to controls. In rodent models, expression of a redox-dead form of PKG1α (PKG1αC42S) reduced adverse cardiac remodeling and preserved function in response to cardiac stress. Compared to WT PKG1α, which localized to the cytosol, ...
5 remained unchanged (Figure 2A) as reported (Renden and von Gersdorff, 2007 and Yamashita et al., 2010). However, after loading. Rp-cGMPS (3 μM), endocytic τ0.5 became slower as depolarizing pulses increased to 5-20 ms (Figure 2A). In the presence of PKG inhibitor, calyceal terminals after hearing (Figure 2A) behave like calyces before hearing (Figure 2B), with the endocytic τ0.5 showing see more a positive correlation with the magnitude of exocytosis. Thus, the PKG-dependent endocytic speeding mechanism matures during the second postnatal week when rodents start to hear sound. At the calyx of Held, repetitive stimulation at 1 Hz accelerates endocytosis to a second-order time constant through a Ca2+-dependent mechanism (Wu et al., 2009 and Yamashita et al., 2010). We asked whether PKG might regulate this rapid endocytosis at P13-P14 calyces. During a short train of stimulation (20 ms depolarizing pulses repeated at 1 Hz for 20 s), as exocytic ΔCm summed up to a high level, the endocytic ...
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There is growing evidence for the antitumor effects of cGMP-dependent protein kinase (PKG) in colon cancer cells. We reported recently that ectopically expressed PKG resulted in defective angiogenesis in xenografts, and was associated with reduced levels of vascular-endothelial growth factor (VEGF). In order to better understand the therapeutic potential of this enzyme, the present work has examined the mechanism of VEGF regulation by PKG. In contrast to the SW620 xenografts, PKG had no effect on VEGF expression in SW620 cells grown under standard tissue culture conditions in vitro. However, the increase in VEGF expression observed when the cells were subjected to hypoxic stress was significantly attenuated by PKG at both the mRNA and protein levels. Using luciferase reporter assays, PKG was shown to inhibit hypoxia inducible factor (HIF) transcriptional activity in several colon cancer cell lines, including SW620, HCT116, and HT29. The attenuation of HIF by PKG reflected a more fundamental ...
TY - JOUR. T1 - Identification of cGMP-Dependent protein kinase anchoring proteins (GKAPs). AU - Vo, Ngan. AU - Gettemy, Jessica M.. AU - Coghlan, Vincent M.. PY - 1998/5/29. Y1 - 1998/5/29. N2 - To promote both efficiency and selectivity, many protein kinases and phosphatases are maintained in specific subcellular microenvironments through their association with anchoring proteins. In this study, we describe a new class of proteins, called GKAPS, that specifically bind the Type II cGMP-dependent protein kinase (PKG). GKAPs were detected in rat aorta, brain, and intestine using a protein overlay technique. The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore, a synthetic peptide that blocks association of PKA with AKAPs did not affect the PKG-GKAP interaction. Deletion mutagenesis was used to map the GKAP binding determinants within PKG to the N-terminal regulatory region. While most GKAPs were tissue-specific, a ...
GF ID PRKG1_interact #=GF AC PF15898.5 #=GF DE cGMP-dependent protein kinase interacting domain #=GF AU Eberhardt R;0000-0001-6152-1369 #=GF SE Jackhmmer:A8JNT6 #=GF GA 32.40 32.40; #=GF TC 33.30 32.50; #=GF NC 32.30 32.30; #=GF BM hmmbuild HMM.ann SEED.ann #=GF SM hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq #=GF TP Family #=GF RN [1] #=GF RM 12873707 #=GF RT Dimerization of cGMP-dependent protein kinase 1alpha and the #=GF RT myosin-binding subunit of myosin phosphatase: role of leucine #=GF RT zipper domains. #=GF RA Surks HK, Mendelsohn ME; #=GF RL Cell Signal. 2003;15:937-944. #=GF RN [2] #=GF RM 10567269 #=GF RT Regulation of myosin phosphatase by a specific interaction with #=GF RT cGMP- dependent protein kinase Ialpha. #=GF RA Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, #=GF RA Lincoln TM, Mendelsohn ME; #=GF RL Science. 1999;286:1583-1587. #=GF DR INTERPRO; IPR031775; #=GF DR SO; 0100021; polypeptide_conserved_region; #=GF CC This domain is found at the C-terminus ...
Intracellular cAMP and cGMP levels are increased in response to a variety of hormonal and chemical stimuli; these nucleotides play key roles as second messenger signals in modulating myriad physiological processes. The cAMP-dependent protein kinase and cGMP-dependent protein kinase are major intrace …
Aim: To determine whether Ca2+/calcineurin mediated the inhibitory effects of nitric oxide /cGMP-dependent protein kinase (NO/PKG) on the proliferation of vascular smooth muscle cells (VSMC). Methods: Proliferation and viability of primary VSMC from rat aorta were measured using [3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] (MTT) assay and acridine orange and ethidium bromide staining, respectively. Cytosolic Ca2+ was determined by Fluo-3/AM. Calcineurin protein and its activity were assayed using immunoblotting and free inorganic phosphate analysis, respectively. Results: (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) and Sp-8-(4-chlorophenylthio)-guanosine-3′,5′-cyclic monophosphorothioate (Sp-8-pCPT-cGMPS) decreased phenylephrine (PE)-induced proliferation of VSMC by 27.3% and 36.6%, respectively, but Rp-8-[4-chlorophenyl)thio]-guanosine-3′,5′-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS) increased PE-induced proliferation of VSMC. SNAP, Sp-8-pCPT-cGMPS, and ...
Imidazoline compounds have been considered for the treatment of type 2 diabetes. We have now investigated the effects of imidazolines on interleukin (IL)-1beta-induced beta-cell apoptosis and the signal transduction pathways involved. Inhibition of Ca2+ influx into beta-cells by D-600, a blocker of voltage-gated L-type Ca2+ channels, suppressed IL-1beta-induced apoptosis. Our data show that calcineurin, Ca2+/calmodulin-dependent serine/threonine protein phosphatase 2B, is responsible for the effect of Ca2+ on beta-cell apoptosis. We also demonstrate that IL-1beta-mediated apoptosis correlates with expression of inducible nitric oxide synthase (iNOS) and the increase in intracellular production of nitric oxide. An inhibitor of cGMP-dependent protein kinase (PKG), KT5823, suppressed IL-1beta-induced apoptosis, suggesting the involvement of a PKG-dependent pathway in the apoptotic process. One of the major findings in this study is that imidazoline compounds RX871024 and efaroxan, suggested as ...
Stimulation of protein kinase G (PKG) suppresses maladaptive cardiac hypertrophy in part by blunting signaling cascades such as calcineurin/NFAT (Cn) and calcium-calmodulin dependent kinase II (CamKII). Here we report PKG stimulation also enhances autophagy as an anti-hypertrophic mechanism, identify a novel phosphorylation target for this effect, and show this signaling is blunted when PKG becomes oxidized at cysteine 42 (C42). Mice with knock-in expression of mutant PKG (C42S) or littermate controls were subjected to pressure-overload. C42S mice were protected, with reduced hypertrophy and fibrosis, improved function, and blunted Cn, CamKII, and hypertrophic gene activation. Neonatal rat ventricular myocytes (NRVMs) expressing C42S-PKG exposed to 48hr endothelin-1 (ET1) also displayed less hypertrophic responses. In both C42S mice and NRVMs expressing C42S, autophagic flux was increased over WT, determined by autophagic flux assays, which was associated with inhibited mammalian target of ...
In this study, we identified PKG2 to be a novel K-Ras kinase that phosphorylates K-Ras at Ser181 in response to activation of AMPK. PKG is activated by the AMPK-mediated activation of eNOS, which generates cGMP through NO activation of soluble guanylyl cyclase. Using multiple activators of this pathway to drive K-Ras phosphorylation, we identified two separate consequences of K-Ras phosphorylation. Phospho-K-RasG12V laterally segregates from nonphospho-K-RasG12V to form nanoclusters that acutely retune the K-Ras signal output to enhance both phosphatidylinositol 3-kinase-Akt and Raf-MAPK activation. This is mitigated, however, by a progressive loss of phosphorylated K-Ras from the PM, which subsequently abrogates K-Ras signaling. Thus, AMPK activation can both retune K-Ras signaling and silence it.. The identification of PKG2 among the three expressed isoforms of PKG as the K-Ras kinase is based on several observations. First, knockdown of PKG2 expression was sufficient to completely abolish ...
Two disparate mechanisms have evolved for activating PKG1α; one relies on binding of the second messenger cGMP, the other involves thiol oxidation inducing a disulfide homodimer. In this study, we found that these 2 mechanisms of activating PKG1α are intricately linked with the binding of cGMP preventing oxidation to the disulfide state. The N-terminus of PKG1α, which contains the redox-sensitive cysteine from each monomer of the dimer, have been mapped using NMR.14 This structural information shows that the redox cysteines in PKG1α are in close proximity and orientated to allow the formation of a disulfide bond when oxidants are present. Our observations are consistent with cGMP binding to PKG1α causing an allosteric structural change that reorientates the redox cysteines. This reorientation presumably moves the thiols too far apart or changes their molecular environment such that their pKa is increased to lower their reactivity with oxidants, either of which would attenuate disulfide ...
Dynamic regulation of arterial tone influences blood pressure and flow, and ultimately plays a critical role in cardiovascular health and disease. My research focuses primarily on cellular signaling pathways that impair excitation-contraction coupling in vascular smooth muscle (VSM), thereby reducing contractility and promoting vasodilation. In particular, I am interested in mechanisms that provide constant or tonic modulation of vascular tone by controlling membrane potential, intracellular Ca2+ and the sensitivity of the contractile apparatus to Ca2+. My projects have investigated mechanisms of cyclic nucleotide vasorelaxation, including the pivotal roles of phosphodiesterases and cyclic nucleotide dependent protein kinases. Recent studies using a novel class of cGMP-dependent protein kinase (PKG) inhibitors suggest a critical vasoregulatory role for constitutively active PKG in VSM.. The vascular endothelium (a single layer of cells lining the lumen of the entire vasculature) constantly ...
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cAMP- and cGMP-dependent protein kinases (cAPK and cGPK). Both types of kinases contains two tandem copies of the cyclic nucleotide-binding domain. The cAPKs are composed of two different subunits: a catalytic chain and a regulatory chain which contains both copies of the domain. The cGPKs are single chain enzymes that include the two copies of the domain in their N- terminal section. The nucleotide specificity of cAPK and cGPK is due to an amino acid in the conserved region of β-barrel 7: a threonine that is invariant in cGPK is an alanine in most cAPK ...
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Author: behdad Update of /cvs/pkgs/rpms/pango/devel In directory cvs1.fedora.phx.redhat.com:/tmp/cvs-serv19752 Modified Files: .cvsignore pango.spec sources Log Message: 1.26.1 Index: .cvsignore =================================================================== RCS file: /cvs/pkgs/rpms/pango/devel/.cvsignore,v retrieving revision 1.97 retrieving revision 1.98 diff -u -p -r1.97 -r1.98 --- .cvsignore 21 Sep 2009 21:26:25 -0000 1.97 +++ .cvsignore 3 Dec 2009 21:12:36 -0000 1.98 @@ -1 +1 @@ -pango-1.26.0.tar.bz2 +pango-1.26.1.tar.bz2 Index: pango.spec =================================================================== RCS file: /cvs/pkgs/rpms/pango/devel/pango.spec,v retrieving revision 1.179 retrieving revision 1.180 diff -u -p -r1.179 -r1.180 --- pango.spec 21 Sep 2009 21:26:25 -0000 1.179 +++ pango.spec 3 Dec 2009 21:12:36 -0000 1.180 @@ -8,7 +8,7 @@ Summary: System for layout and rendering of internationalized text Name: pango -Version: 1.26.0 +Version: 1.26.1 Release: 1%{?dist} License: ...
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Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
Its important to have someone you trust care for your pet while youre away. Keeping your pet at home in the care of a pet sitter will spare your pet the stress and health risks associated with boarding facilities. A pet sitter will not only feed and play with your pet but also water plants, bring in the mail, and take out the trash. Some sitters may also perform grooming or behavior training. A pet sitter can help your home appear to be lived in, which can deter burglars. If you dont have a neighbor, friend, or relative who can care for your pet when youre away, consider hiring a professional pet sitter. Knowing that your pet is being cared for by a professional pet sitter can add to your peace of mind while youre away.. Read More ...
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Complete information for PRKG2 gene (Protein Coding), Protein Kinase CGMP-Dependent 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Histamines are present in many foods, especially those that have been aged. Foods with the highest histamine levels are aged cheeses, yogurt, sour cream, meats, salami, bacon, wine, sauerkraut, pickles, soy sauce, and vinegar. However, they are also found in some fresh fruits and vegetables like spinach, tomatoes, papaya, pineapple, strawberries, eggplant, and citrus fruits.…
Histamines are present in many foods, especially those that have been aged. Foods with the highest histamine levels are aged cheeses, yogurt, sour cream, meats, salami, bacon, wine, sauerkraut, pickles, soy sauce, and vinegar. However, they are also found in some fresh fruits and vegetables like spinach, tomatoes, papaya, pineapple, strawberries, eggplant, and citrus fruits.…
Boerth NJ, Dey NB, Cornwell TL, Lincoln TM (1997). "Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell ... 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 ... Ethylene is perceived by a family of five transmembrane protein dimers such as the ETR1 protein in Arabidopsis. The gene ...
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 ... Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), ... including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to ...
In vivo phosphorylation of thromboxane by cyclic GMP-dependent protein kinase". Proceedings of the National Academy of Sciences ... Nitric oxide (NO) stimulates cGMP production and therefore the activation cGMP-dependent protein kinase (G kinase). This kinase ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). These signaling elements include ... Siess, Wolfgang; Eduardo, Lapetina (1990). "Functional relationship between cyclic AMP-dependent protein phosphorylation and ...
Protein kinase activationEdit. cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein ... 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 ... Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are 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 ... an enzyme called protein kinase A (PKA).[12]. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ... "Multiple pathway signal transduction by the cAMP-dependent protein kinase". FASEB J. 8 (15): 1227-36. doi:10.1096/fasebj.8.15. ...
While studying cyclic GMP, Ignarro read a paper by Ferid Murad, who demonstrated that nitric oxide elevates cyclic GMP levels. ... 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. ... Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. ...
"Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... Roskoski R, Roskoski LM (Jan 1987). "Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second ... that are phosphorylated by a variety of protein kinases.[12][25] Ser40 is phosphorylated by the cAMP-dependent protein kinase.[ ... is phosphorylated by the calcium-calmodulin-dependent protein kinase.[27] MAPKAPK2 (mitogen-activated-protein kinase-activating ...
Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). ... This activity is dependent on cytosolic DNA. cGAS catalyzes formation of cGAMP in the presence of dsDNA. cGAS directly binds ... STING is also thought to activate the NF-κB transcription factor through the activity of the IκB kinase (IKK), though the ... Cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide (CDN) and the first to be found in metazoans. Other CDNs (c-di-GMP and c-di-AMP ...
... through a protein kinase C-dependent mechanism". Biochem J. 466 (2): 379-390. doi:10.1042/bj20140881. PMID 25422863.. ... Pugh Jr, E. N.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in vertebrate ... Activation of protein kinase C. Further reading: Function of protein kinase C. ... Calcium coordination plays an important role in defining the structure and function of proteins. An example a protein with ...
IkB kinase EC 2.7.11.11: cAMP-dependent protein kinase EC 2.7.11.12: cGMP-dependent protein kinase EC 2.7.11.13: protein kinase ... cyclic GMP-AMP synthase EC 2.7.8.1: diacylglycerol ethanolaminephosphotransferase EC 2.7.8.2: diacylglycerol ... mitogen-activated protein kinase EC 2.7.11.25: mitogen-activated protein kinase kinase kinase EC 2.7.11.26: tau-protein kinase ... mitogen-activated protein kinase kinase EC 2.7.13.1: protein-histidine pros-kinase EC 2.7.13.2: protein-histidine tele-kinase ...
Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase ... Protein splicing[edit]. Main article: Protein splicing. In addition to RNA, proteins can undergo splicing. Although the ... 3'OH of a free guanine nucleoside (or one located in the intron) or a nucleotide cofactor (GMP, GDP, GTP) attacks phosphate at ... NAD-dependent 2'-phosphotransferase then removes the 2'-phosphate group.[22][23] ...
Ca2+/calmodulin-dependent protein kinases or CaM kinases. are primarily regulated by the Ca2+/calmodulin complex. ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Protein kinase C ('PKC'). is actually a family of protein kinases consisting of ~10 isozymes. They are divided into three ... Dephospho-(reductase kinase) kinase (EC 2.7.11.3). *AMP-activated protein kinase α *PRKAA1 ...
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). ...
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)[1] is a form of phosphoprotein phosphatase that acts upon phosphorylated serine/ ...
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 ... Guanylyl cyclase activator (protein). References[edit]. *^ Sakurai K.; Chen J.; Kefalov V. (2011). "Role of guanylate cylcase ... Guanylate cyclase is often part of the G protein signaling cascade that is activated by low intracellular calcium levels and ...
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[edit]. 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 ...
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 ...
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.[17] ...
1975). "Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: the Yin Yang hypothesis". Adv Cyclic ... Protein phosphatase *PP2A. *OCRL. *Pyruvate dehydrogenase phosphatase. *Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase ... "Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability". Blood. 105 (9 ... "Positive inotropic effect of the inhibition of cyclic GMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase (PDE2) on guinea ...
protein domain specific binding. • receptor serine/threonine kinase binding. • peroxisome proliferator activated receptor ... Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM (March 2000). "Mdm2 is a RING finger-dependent ubiquitin protein ligase ... cellular response to organic cyclic compound. • viral process. • response to iron ion. • regulation of gene expression. • ... protein binding. • enzyme binding. • metal ion binding. • identical protein binding. • ubiquitin protein ligase binding. • p53 ...
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 ... cAK indicates cAMP-dependent protein kinase; cGK(I/II), cGMP-dependent protein kinase (type I/II); cGMP, cyclic guanosine-3′,5 ...
... cyclic AMP-dependent protein kinase; cGK, cyclic GMP-dependent protein kinase; FAK, focal adhesion kinase; GBSS, Geys balanced ... VASP is a prominent substrate for both cGMP-dependent protein kinase (cGK) and cAMP-dependent protein kinase. Evidence ... Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly. J. Cell ... Progress in understanding the mechanism and function of cyclic GMP-dependent protein kinase. Adv. Pharmacol. 26: 115. ...
... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ... phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase ...
Cyclic GMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010;62:525- ... Regulation and role of myocyte cyclic GMP-dependent protein kinase-1. Proc Natl Acad Sci U S A. 2010;107:E98. ... The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 2005;280:1-4. ... cGMP-dependent protein kinase I. RGS. regulator of G protein-coupled signaling. TnI. troponin I. ...
... reduction of Ca2+ by atripeptin and 8-bromo-cyclic GMP is mediated by cyclic GMP-dependent protein kinase. J Biol Chem 264: ... guanosine monophosphate and activating cyclic 3′,5′-guanosine monophosphate-dependent protein kinase. This results in a ... 11) NO production rate (RNO) by endothelial NO synthase is dependent on endothelial O2 availability, and the amount of O2 ... Shear stress-dependent production of NO was not considered in the present study, but should be investigated in future ...
... cyclic monophosphorothioate (10 microM), cyclic guanosine 3,5 monophosphate-dependent protein kinase (PKG) inhibitors with ... perhaps dependent on the second-messenger cyclic ADP ribose. ... NO-dependent LTD involving activation of guanylyl cyclase, ... We used the stable NO donor S-nitroso-N-acetylpenicillamine (SNAP) to study the NO-dependent form of LTD at Schaffer collateral ... two cell-permeant antagonists of the cyclic ADP-ribose binding site on ryanodine receptors also were able to block the ...
Calcium-Binding Proteins * Cyclic GMP-Dependent Protein Kinases * Enzyme Inhibitors * Erythrocytes * Host-Parasite Interactions ... The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of ... We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of ... A plant-like kinase in plasmodium falciparum regulates parasite egress from erythrocytes Academic Article ...
Research Grants about cyclic gmp dependent protein kinases ... cyclic gmp dependent protein kinases. Summary. Summary: A group ... cyclic nucleotide regulated protein kinases , cyclic gmp dependent protein kinases ... cyclic amp dependent protein kinases*enzyme inhibitors*phosphorylation*carbazoles*cyclic amp*thionucleotides*protein kinase ... Toxoplasma gondii cyclic GMP-dependent kinase: chemotherapeutic targeting of an essential parasite protein kinase. Robert G K ...
Cyclic-GMP-dependent protein kinase inhibits the Ras/mitogen-activated protein kinase pathway. Mol Cell Biol 1998;18:6983-94. ... increase cellular cyclic GMP and subsequently activate cyclic GMP-dependent protein kinase (PKG); (b) activate c-jun NH2- ... Sulindac independently modulates extracellular signal-regulated kinase 1/2 and cyclic GMP-dependent protein kinase signaling ... Sulindac independently modulates extracellular signal-regulated kinase 1/2 and cyclic GMP-dependent protein kinase signaling ...
... Waldkirch, ... cavernosum, corpus, cavernous arteries, cyclic gmp, erectile dysfunction, nitric oxide, protein kinase G. in Journal of Sexual ... cyclic gmp,erectile dysfunction,nitric oxide,protein kinase G}, language = {eng}, number = {3}, pages = {536--543}, publisher ... Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue}, url = {http:// ...
Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile ... AMP-activated protein kinase (AMPK). In dissecting the molecular mechanism, we identified cyclic GMP (cGMP)-dependent protein ... We show here that K-Ras is a substrate for cyclic GMP-dependent protein kinases (PKGs). In intact cells, activated PKG2 ... Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent Protein Kinase 2. Kwang- ...
Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome. K. Govindasamy, ... Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome ... Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome ... Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome ...
Cyclic-GMP-dependent protein kinase in smooth muscle and neutrophils.. T. M. Lincoln, K. B. Pryzwansky, T. L. Cornwell, T. A. ... Cyclic-GMP-dependent protein kinase in smooth muscle and neutrophils. / Lincoln, T. M.; Pryzwansky, K. B.; Cornwell, T. L.; ... Cyclic-GMP-dependent protein kinase in smooth muscle and neutrophils. Advances in second messenger and phosphoprotein research ... Lincoln, T. M. ; Pryzwansky, K. B. ; Cornwell, T. L. ; Wyatt, T. A. ; MacMillan, L. A. / Cyclic-GMP-dependent protein kinase in ...
PKG I cyclic GMP-dependent protein kinase type I PKG U cyclic GMP-dependent protein kinase type II pM pico Molar PMSF phenyl ... and cGMP-dependent protein kinases, protein kinase C , calmodulin-dependent protein kinase U and casein kinase LT. Eur J ... Cyclic-GMP-dependent protein kinase inhibits the Ras/Mitogen-activated protein kinase pathway. Mol Cell Biol. 18:6983-94. Surks ... the residues on cyclic GMP-dependent protein kinase that are autophosphorylated in the presence of cyclic A M P and cyclic GMP ...
Boerth NJ, Dey NB, Cornwell TL, Lincoln TM (1997). "Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell ... 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 ... Ethylene is perceived by a family of five transmembrane protein dimers such as the ETR1 protein in Arabidopsis. The gene ...
The cAMP-dependent protein kinase and cGMP-dependent protein kinase are major intrace … ... Cyclic AMP-Dependent Protein Kinases / metabolism* * Cyclic GMP / metabolism* * Cyclic GMP-Dependent Protein Kinases / ... The cAMP-dependent protein kinase and cGMP-dependent protein kinase are major intracellular receptors for these nucleotides, ... Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action Crit Rev Clin Lab Sci. 1999 Aug; ...
Activity of Cyclic GMP-Dependent Protein Kinase in Aortae from Spontaneously Hypertensive Rats. Coquil, Jean-François; Brunelle ...
Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. ... Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. ... Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. ... Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. ...
Cyclic GMP-Dependent Protein Kinases. *Decanoic Acids. *Diazoxide. *Electron Transport Complex I ... Myxothiazol stimulated mitoK(ATP)-dependent ROS production, whereas rotenone had no effect. This indicates that the superoxide ... dependent stimulation of ROS production is unknown. We examined ROS production in suspensions of isolated rat heart and liver ...
Cyclic GMP-dependent protein kinases and the cardiovascular system: insights from genetically modified mice. Circ. Res. 93:907- ... Nonstandard abbreviations used: ANP, atrial natriuretic peptide; cGKI, cGMP-dependent protein kinase I; cGMP, cyclic GMP; DEA- ... Radioimmunoassay of cyclic AMP and cyclic GMP. Adv. Cyclic Nucleotide Res. 10:1-33. View this article via: PubMed Google ... Cyclic GMP levels determined in intact aortic rings of WT, α1 -, and α2 -deficient mice. Cyclic GMP content was determined in ...
Buy a discounted Hardcover of Cyclic GMP online from Australias leading online bookstore. ... Booktopia has Cyclic GMP, Synthesis, Metabolism, and Function: Volume 26 by J. Thomas August. ... Cyclic GMP-dependent protein kinase. * Hormones and ligands that regulate GMP formation and/or metabolism. * Effects of cyclic ... cyclic GMP-dependent protein kinases, and various hormones and ligands that regulate cyclic GMP formation and/or metabolism. ...
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 ... Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG), ... including increased Rho-kinase activity. Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to ...
... suggesting that cGMP-dependent effectors are involved in the control of islet activity. The cGMP-dependent protein kinase type ... Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells. Veronika Leiss, Andreas Friebe, Andrea Welling, Franz ... Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells. Veronika Leiss, Andreas Friebe, Andrea Welling, Franz ... cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium. Circ Res 2002;90:18-20 ...
5-trisphosphate receptor by cyclic GMP-dependent protein kinase, J. Biol. Chem. 269:8701-8707.PubMedGoogle Scholar ... phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles, Proc. ... Effect of cAMP-dependent protein kinase, Am. J. Physiol. 258:C1086-C1091.PubMedGoogle Scholar ... Cyclic AMP-dependent kinase augments inositol trisphosphate-mediated Ca2+ mobilization without increasing the cellular levels ...
Cyclic GMP-dependent protein kinases in protozoa. David A. Baker, Wensheng Deng. [Frontiers In Bioscience, Landmark, 10, 1229 ... Role of protein kinases in neurodegenerative disease: cyclin-dependent kinases in Alzheimers disease. Edward A. Monaco III and ... Molecular properties and biological functions of cGMP-dependent protein kinase II. Arie B. Vaandrager, Boris M. Hogema, Hugo R ... Tracking functions of cGMP-dependent protein kinases (cGK). Suzanne M. Lohmann, Ulrich Walter. [Frontiers In Bioscience, ...
Phosphorylation of NF-kappaB proteins by cyclic GMP-dependent kinase. A noncanonical pathway to NF-kappaB activation pp. 2174- ... The mystery of nonclassical protein secretion. A current view on cargo proteins and potential export routes pp. 2109-2119(11) ... The histidine-phosphocarrier protein of Streptomyces coelicolor folds by a partially folded species at low pH pp. 2254-2267(14 ... Interactions between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host cells pp. ...
We found that a conserved behavioral modulator, cyclic GMP dependent kinase (PKG) may regulate the multifractal kinetics ... LEtoile, N. D. et al. The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron 36, ... Wang, X. & Robinson, P. J. Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J. Neurochem. 68, ... Feil, R., Lohmann, S. M., de Jonge, H., Walter, U. & Hofmann, F. Cyclic GMP-dependent protein kinases and the cardiovascular ...
Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase (By ... Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. ... 3,5-cyclic-GMP phosphodiesterase activity Source: GO_Central ,p>Inferred from Biological aspect of Ancestor,/p> ,p>A type of ... Protein. Similar proteins. Species. Score. Length. Source. P00515. cAMP-dependent protein kinase type II-alpha regulatory ...
Protein Coding), Regulator Of G Protein Signaling 3, including: function, proteins, disorders, pathways, orthologs, and ... Phosphorylated by cyclic GMP-dependent protein kinase. * P49796-RGS3_HUMAN * ISGylated. * P49796-RGS3_HUMAN ... Protein Symbol:. P49796-RGS3_HUMAN. Recommended name:. Regulator of G-protein signaling 3. Protein Accession:. P49796. ... This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the ...
Protein Coding), Regulator Of G Protein Signaling 4, including: function, proteins, disorders, pathways, orthologs, and ... Phosphorylated by cyclic GMP-dependent protein kinase. *P49798-RGS4_HUMAN. * Modification sites at PhosphoSitePlus *P49798 ... G-protein coupled receptor signaling pathway. IEA. --. GO:0008277. regulation of G-protein coupled receptor protein signaling ... Protein Symbol:. P49798-RGS4_HUMAN. Recommended name:. Regulator of G-protein signaling 4. Protein Accession:. P49798. ...
cGMP-dependent protein kinase;. 3:5-cyclic GMP-dependent protein kinase;. cGMP-dependent protein kinase Ibeta;. guanosine 3: ... Progressive cyclic nucleotide-induced conformational changes in the cGMP-dependent protein kinase studied by small angle X-ray ... 5-cyclic monophosphate-dependent protein kinase;. PKG;. PKG 1alpha;. PKG 1beta;. PKG II;. STK23. ... Dimerization of cGMP-dependent protein kinase Ibeta is mediated by an extensive amino-terminal leucine zipper motif, and ...
The level of myosin II phosphorylation is determined by activities of myosin light chain kinase and myosin phosphatase (MP). MP ... EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/Protein Phosphatase 1; ... Cyclic GMP-Dependent Protein Kinases / genetics, metabolism. Gene Expression Regulation, Developmental. Humans. Membrane ... 0/Membrane Proteins; 0/Muscle Proteins; 0/PPP1R14A protein, human; 0/PPP1R16B protein, human; 0/Phosphoproteins; 0/Protein ...
Cyclic GMP in turn activates the cGMP-dependent protein kinase G (PKG). Phosphorylation of Smad3 at S309 and T368 within MH2 by ... PDE5 enzyme degrades cyclic guanosine monophosphate (c-GMP), a molecule responsible for nitric oxide-mediated vasodilatation. ... mitogen-activated protein kinase [MAPK], Rho, etc). TRI phosphorylates Smad3 at the S423/S425 within the C-terminal MH2. The ... Blockade of TSP1 by cyclic GMP partially abolishes the autocrine TGF-b signaling in SSc 﫿broblasts24. Increase in level of cGMP ...
Regulation of gene expression by cyclic GMP-dependent protein kinase requires nuclear translocation of the kinase: ... Cyclic GMP-dependent protein kinase inhibits osteopontin and thrombospondin production in rat aortic smooth muscle cells. Circ ... Boerth, N. J., Dey, N. B., Cornwell, T. L. & Lincoln, T. M. Cyclic GMP-dependent protein kinase regulates vascular smooth ... Guanosine 3′,5′-cyclic monophosphate (cGMP)/cGMP-dependent protein kinase induce interleukin-6 transcription in osteoblasts. ...
  • 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)
  • Finally, two cell-permeant antagonists of the cyclic ADP-ribose binding site on ryanodine receptors also were able to block the induction of LTD. These results support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3',5' cyclic monophosphate and subsequent PKG activation. (ox.ac.uk)
  • The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. (scripps.edu)
  • Tyrosine hydroxylase purified from rat pheochromycytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. (elsevier.com)
  • Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP-dependent protein kinases. (elsevier.com)
  • The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following HPLC. (elsevier.com)
  • These data provide support for the notion that the protein kinases are phosphorylating the same residue of tyrosine hydroxylase. (elsevier.com)
  • Long-term depression (LTD) of synaptic transmission can be induced by several mechanisms, one thought to involve Ca2+-dependent activation of postsynaptic nitric oxide (NO) synthase and subsequent diffusion of NO to the presynaptic terminal. (ox.ac.uk)
  • Induction of hippocampal LTD requires nitric-oxide-stimulated PKG activity and Ca2+ release from cyclic ADP-ribose-sensitive stores. (ox.ac.uk)
  • 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)
  • We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. (scripps.edu)
  • 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)
  • B, Selected properties of cGMP-dependent protein kinases. (ahajournals.org)
  • 6 Like NO, cGMP can affect multiple signaling pathways ( Figure 1 A). 1,5,6 To date, three classes of cGMP receptor proteins have been identified: cyclic nucleotide-gated (CNG) cation channels, cGMP-regulated PDEs, which hydrolyze cAMP and/or cGMP, and cGMP-dependent protein kinases (cGKs). (ahajournals.org)
  • The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). (elsevier.com)
  • Interestingly, a homolog of EGL-4 in Drosophila was shown to play a role in natural variation of foraging behavior, indicating a conserved role of cGMP-dependent protein kinases as a modulator of interspecies behaviors. (pnas.org)
  • 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)
  • Activator of Epac, cAMP and cGMP-dependent protein kinases (PKA/PKG). (abcam.com)
  • In addition, two different cGMP-dependent protein kinases (cGKI and cGKII) have been identified in mammals (6, 7). (diva-portal.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 cGMP-dependent protein kinase type I (cGKI) is an important intracellular mediator of NO/cGMP signaling in many cells ( 22 ). (diabetesjournals.org)
  • The cAMP-dependent protein kinase and cGMP-dependent protein kinase are major intracellular receptors for these nucleotides, and the actions of these enzymes account for much of the cellular responses to increased levels of cAMP or cGMP. (nih.gov)
  • C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). (elsevier.com)
  • In the vascular system, the receptor for the signaling molecule NO, guanylyl cyclase (GC), mediates smooth muscle relaxation and inhibition of platelet aggregation by increasing intracellular cyclic GMP (cGMP) concentration. (jci.org)
  • Research conducted thus far has led to the identification of several important regulatory mechanisms for leukocyte degranulation, including elevation of intracellular Ca 2+ concentration, activation of the cytoskeletal contractile apparatus, and phosphorylation of the soluble N -ethylmaleimide-sensitive factor-attachment protein (SNAP) 3 receptor proteins (SNAREs). (jimmunol.org)
  • The intracellular signals that regulate the activity-dependent development of connections in the mammalian brain are virtually unknown. (jneurosci.org)
  • 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)
  • By increasing the intracellular concentrations of cyclic guanosine monophosphate (cGMP), phosphodiesterase-5 (PDE5) inhibitors such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) have been used therapeutically to treat erectile dysfunction ( 12 ), pulmonary hypertension ( 13 ), and cardiac hypertrophy ( 14 ). (rupress.org)
  • The effect of pH on cerebral vascular tone is mediated by nitric oxide (NO), prostanoids, cyclic nucleotides, potassium channels, and intracellular calcium. (asahq.org)
  • The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the kinase peptides of the present invention. (patentgenius.com)
  • A group of enzymes that are dependent on cyclic GMP and catalyzes the phosphorylation of serine or threonine residues of proteins. (labome.org)
  • These accumulated findings provide insights into the mechanisms by which these enzymes produce their specific physiological effects and are helpful in considering the actions of other protein kinases as well. (nih.gov)
  • It appears that for such events a supramolecular complex is required that comprises of the appropriate effector system together with signal termination enzymes such as PDEs and phosphatases that are sequestered by scaffolding proteins ( 4 ). (mcponline.org)
  • In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy. (rupress.org)
  • The kinases comprise the largest, known protein group, a superfamily of enzymes with widely varied functions and specificities. (patentgenius.com)
  • We found marked inhibition of AngII-induced Rho/Rho-kinase activation and subsequent VSMC migration by eNOS gene transfer whereas G q -dependent transactivation of the epidermal growth factor receptor by AngII remains intact. (ahajournals.org)
  • In this regard, AngII stimulates hypertrophy, proliferation, and migration of vascular smooth muscle cells (VSMCs) through a G protein-coupled receptor (GPCR), the AngII type-1 receptor (AT 1 ). (ahajournals.org)
  • Recent accumulating evidence suggests that induction of VSMC migration by the AT 1 receptor requires multiple sets of downstream tyrosine and serine/threonine kinases. (ahajournals.org)
  • 3 Among these kinases, we and others have demonstrated that extracelluar-signal regulated kinase (ERK) activated through "trans"-activation of the epidermal growth factor receptor (EGFR) and Rho-kinase (ROCK), an effecter of a small G protein, Rho, are critical for VSMC migration induced by AngII. (ahajournals.org)
  • Cytosolic cGMP controls the activity of diverse receptor proteins, including the cGMP-dependent protein kinase (cGK). (jneurosci.org)
  • These results suggest that PKG and PI3K are involved in degranulation, possibly through phosphorylation of target membrane SNAP receptor proteins and their binding proteins. (jimmunol.org)
  • Using pharmacological, transfection, and in vitro phosphorylation experiments, we demonstrate that AMP-activated protein kinase subunit alpha 1 (AMPKα1) is activated by estrogen receptor stimulation and catalyzes RhoA phosphorylation induced by E2. (ahajournals.org)
  • 5 Recently, we showed that stimulation of angiotensin II type 2 receptor (AT 2 R) in VSMC induces RhoA phosphorylation by the Ste20-related kinase SLK, which contributes to the vasodilatory effect of AT 2 R. 8 In fact, functional consequences of RhoA phosphorylation mimics RhoA-Rock inhibition that reverses or delays vascular pathology development. (ahajournals.org)
  • There have been numerous putative non-COX-related NSAID targets including β-catenin ( 9 ), Ras ( 10 ), nuclear factor-κB ( 11 ), cyclic GMP ( 12 ), peroxisome proliferator-activated receptor δ ( 13 ), NSAID-activated gene-1 ( 14 ), epidermal growth factor receptor ( 15 ), prostate apoptosis response gene-4 ( 16 ), etc. (aacrjournals.org)
  • The negative inotropism was insensitive to losartan and CGP42112 (AT 1 and AT 2 ANG II receptor antagonists, respectively), and was abrogated by the AT 1 receptor antagonist CV11974, the G protein blocker pertussis toxin (PTx) and the muscarinic antagonist atropine. (biologists.org)
  • We designed duplex siRNA targeting constructs to knock down selected signaling proteins in bovine aortic endothelial cells (BAEC), and explored receptor-mediated changes in cGMP pathways. (ahajournals.org)
  • Cell lysates were examined by immunoblots for EGF receptor and the MAP kinase ERK (both the activated [phosphorylated] and total protein is shown) and for apoptosis as measured by the presence of cleaved caspase. (ucdenver.edu)
  • Mechanism of regulation of receptor histidine kinases. (embl-heidelberg.de)
  • In the dual signaling mechanism of PST receptor, mostly PST activates Gαq /11 protein leads to the activation of phospholipase C β3-isoform, therefore increasing cytoplasmic free calcium and stimulating protein kinase C. PST inhibits the cell growth in rat HTC hepatoma cells, mediated by nitric oxide and cyclic GMP production. (physiology.org)
  • Estrogen-mediated neuroprotection is probably mediated by both receptor-dependent and -independent mechanisms. (elsevier.com)
  • Ca 2+ -dependent activation of Rho and Rho kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction," Circulation Research , vol. 93, no. 6, pp. 548-556, 2003. (hindawi.com)
  • Lin, Y.F., Browning, M.D., Dudek, E.M. and Macdonald, R.L. Protein kinase C enhances bovine α1β1γ2L GABA A receptor whole-cell currents expressed in L929 fibroblasts. (ucdavis.edu)
  • Lin, Y.F. Regulation of recombinant GABAA receptor function by Ca2+/phospholipid-dependent protein kinase (PKC) phosphorylation. (ucdavis.edu)
  • Lin, Y.F., Angelotti, T.P., Dudek, E.M., Browning, M.D. and Macdonald, R.L. Protein kinase C phosphorylation of the α1β1γ2L subunits of the GABAA receptor enhances whole-cell currents expressed in L929 fibroblasts. (ucdavis.edu)
  • Potently inhibits cyclic GMP-specific phosphodiesterase (PDE Va), PDE III and PDE IV (IC 50 values are 0.9, 24 and 25 μM, respectively). (abcam.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)
  • c-di-GMP caused a persistent increase in cAMP, which still occurred in mutants lacking the adenylate cyclases ACG or ACR, or the cAMP phosphodiesterase RegA. (pnas.org)
  • It has been suggested that cyclic nucleotides (cAMP and cGMP) participate in the regulation of cardiac contractility and glycolysis. (springer.com)
  • Cyclic nucleotides are not involved in either of these phenomena. (springer.com)
  • Effects of sodium nitroprusside, nitroglycerin and sodium azide on levels of cyclic nucleotides and mechanical activity of various tissues. (springer.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 first section focuses on the detailed pharmacology and chemistry of cyclic nucleotides, including their formation, degradation, measurement, and interaction with various modulatory agents, such as receptors and calcium. (springer.com)
  • Bioactivatable, membrane-permeant analogs of cyclic nucleotides as biological tools for growth control of C6 glioma cells. (abcam.com)
  • The authors review what is known about the deleterious effects of sickling on the genitourinary tract and how the role of cyclic nucleotides signaling and protein kinases may help understand the pathophysiology underlying these manifestations and develop novel therapies in the setting of urogenital disorders in sickle cell disease. (hindawi.com)
  • This paper focuses on how previous, sometimes poorly explained, clinical observations of urogenital disorders in patients with SCD relate to more recent discoveries on the role of cyclic nucleotides and protein kinases in the pathophysiology of sickle vaso-occlusion. (hindawi.com)
  • Inhibition of ERK1/2 with U0126 induces apoptosis but fails to activate JNK phosphorylation or down-regulate β-catenin protein expression. (aacrjournals.org)
  • Ras proteins are small GTPases that regulate important cellular signaling cascades to control cell growth, proliferation, and differentiation ( 1 ). (asm.org)
  • We found that a conserved behavioral modulator, cyclic GMP dependent kinase (PKG) may regulate the multifractal kinetics underlying an animal behavior. (nature.com)
  • This protein negatively regulate signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm. (genecards.org)
  • Because several BH3-only family proteins are also expressed in the adult nervous system of mammals, we suggest that studying egl-1 expression in URX may shed light on mechanisms that regulate conserved family members in higher organisms. (g3journal.org)
  • Despite their important role in initiating programmed cell death and likely other cellular processes, our understanding of the factors that regulate BH3-only proteins is incomplete. (g3journal.org)
  • Kinases regulate many different cell proliferation, differentiation, and signaling processes by adding phosphate groups to proteins. (patentgenius.com)
  • Biologic regulation through opposing influences of cyclic GMP and cyclic AMP: The yin yang hypothesis. (springer.com)
  • 3 In addition to this regulation and independently of GDP-GTP cycling, recent reports have proposed that phosphorylation/dephosphorylation cycle also controls Rho protein activity. (ahajournals.org)
  • Modification of focal adhesion structure by PI 3-kinase and its lipid product, PtdIns (3,4,5)-P 3 , has important implications for the regulation of cellular adhesive strength and motility. (rupress.org)
  • Direct Binding and Regulation of RhoA by Cyclic GMP-dependent Protein Kinase Ia. (tuftsmedicalcenter.org)
  • We propose that altered recognition of the catalytic domain by DHp, rather than a shift in position of the phospho-accepting histidine, forms the basis for regulation of kinase activity. (embl-heidelberg.de)
  • Lin, Y.F., Jan, Y.N. and Jan, L.Y. Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cell. (ucdavis.edu)
  • Thus, it may reduce oxidised proteins (e.g., disulfides) back to a thiol state, thereby changing enzyme activity to achieve regulation. (bl.uk)
  • Furthermore, the infusion of specific inhibitors of sGC or protein kinase G (PKG), a target of cGMP, prevents sublamination in vivo . (jneurosci.org)
  • 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)
  • Tyrosine hydroxylase purified from rat pheochromycytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. (elsevier.com)
  • This review summarizes many studies that have contributed significantly to an improved understanding of the catalytic, regulatory, and structural properties of these protein kinases. (nih.gov)
  • Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. (creativebiomart.net)
  • Recent studies of proteins containing kinase-like domains that lack catalytic residue(s) classically required for phosphotransfer, termed pseudokinases, have uncovered important roles in cell signalling across the kingdoms of life. (embl-heidelberg.de)
  • The Plasmodium falciparum genome encodes a number of proteins putatively involved in calcium signaling, including calmodulin-related proteins, a calcium-transporting ATPase, and a family of CDPKs, which are composed of a protein kinase catalytic domain fused to a calcium-binding domain. (asmscience.org)
  • Almost all kinases contain a similar 250-300 amino acid catalytic domain. (patentgenius.com)
  • 1. Exploring novel anti-remodeling molecules regulated by the signaling molecule PKGI: Multiple pre-clinical studies have identified augmentation of cGMP, and its downstream effector protein kinase G (PKG) as inhibiting pathologic cardiac remodeling. (tuftsmedicalcenter.org)
  • Sulindac downregulates both pEGFR and total EGFR and pERK by 12 hours in a dose dependent manner without affecting total ERK levels and it induces apoptosis by 24 hours. (ucdenver.edu)
  • We previously reported that cyclic diguanylate (c-di-GMP), synthesized by diguanylate cyclase A (DgcA), induces stalk formation. (pnas.org)
  • Increased levels of Rho-kinase inhibit myosin phosphatase activity, leading to increased calcium sensitivity and hypercontraction. (wikipedia.org)
  • Reduced Rho-kinase activity permits an increase in myosin phosphatase activity, decreasing the calcium sensitivity of the smooth muscle. (wikipedia.org)
  • Several chapters also deal with some of the effects of cyclic GMP on other second messengers such as calcium ion transport and smooth muscle relaxation. (booktopia.com.au)
  • Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension," Nature , vol. 389, no. 6654, pp. 990-994, 1997. (hindawi.com)
  • The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein. (ntu.edu.sg)
  • Mechanical stimulation is crucial for bone growth and remodeling, and fluid shear stress promotes anabolic responses in osteoblasts through multiple second messengers, including nitric oxide (NO). NO triggers production of cyclic guanosine 3′,5′-monophosphate (cGMP), which in turn activates protein kinase G (PKG). (sciencemag.org)
  • Gene Ontology (GO) annotations related to this gene include GTPase activator activity and G-protein alpha-subunit binding . (genecards.org)
  • Each G protein contains an alpha-, beta- and gamma-subunit and is bound to GDP in the 'off' state. (genecards.org)
  • The α subunit is subject to direct phosphorylation by cyclic GMP-dependent protein kinase (PKG) and dephosphorylation by protein phosphatase 2A. (fishersci.com)
  • Although specific protein-protein interactions between many focal adhesions proteins have been identified, it is not clear how this multimeric complex of proteins organize to form a focal adhesion. (rupress.org)
  • Proteins interacting with cloning scars: a source of false positive protein-protein interactions. (embl-heidelberg.de)
  • this study highlights the importance of conducting careful follow-up studies where novel protein-protein interactions are suspected. (embl-heidelberg.de)
  • phosphorylation of other titin sites could affect protein-protein interactions. (elsevier.com)
  • Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. (lu.se)
  • We now illustrate how these conformational changes are propagated to a downstream domain by fusing Af1503 HAMP variants to the DHp domain of EnvZ, a bacterial histidine kinase. (embl-heidelberg.de)
  • We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. (ntu.edu.sg)
  • Full length wt PKG II and wt regulatory PKG JJ proteins, when overexpressed in hippocampal neurons targeted to the synapse, however, a G2A PKG II mutant, which does not undergo myristoylation had a much more diffuse distribution in the entire cell and did not target to the synapse. (ubc.ca)
  • Some of the best described scaffolding proteins are the so-called A-kinase anchoring proteins (AKAPs), which all bind specifically to the N-terminal dimerization domain of the PKA regulatory domain. (mcponline.org)
  • Publisher Correction: A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis. (nih.gov)
  • 7-10 We have recently reported that eNOS gene transfer activates the NO/cyclic GMP (cGMP)/protein kinase G (PKG) cascade and inhibits VSMC hypertrophy induced by AngII. (ahajournals.org)
  • Division of labor in honey bee colonies is influenced by the foraging gene ( Amfor ), which encodes a cGMP-dependent protein kinase (PKG). (biologists.org)
  • This gene encodes a member of the regulator of G-protein signaling (RGS) family. (genecards.org)
  • RGS3 (Regulator Of G Protein Signaling 3) is a Protein Coding gene. (genecards.org)
  • 20-hydroxyeicosatetraeonic acid (20-HETE), the ω-hydroxylation metabolite of arachidonic acid (AA), is produced by cytochrome P -450 monooxygenases of the (CYP4A and CYP4F gene) families in an NADPH-dependent manner ( 49 ). (physiology.org)
  • We show herein that induction of the tumor suppressor gene COOH-terminal Src kinase (Csk) by NSAID is important for their antiproliferative and hence chemopreventive effects. (aacrjournals.org)
  • The hCHGA gene is located on chromosome 14q32.12, which spans 12,192 bp and gives rise to a transcript of 2,041 bp that encodes a 439-amino acid (aa) mature protein ( 85 ). (physiology.org)
  • We thus proposed that the estrogen-mediated gene induction of Trx plays a pivotal role in the promotion of neuroprotection because Trx is a multifunctional antioxidative and antiapoptotic protein. (elsevier.com)
  • However, both inhibition of adenylate cyclase A (ACA) with SQ22536 and incubation of a temperature-sensitive ACA mutant at the restrictive temperature prevented c-di-GMP-induced cAMP synthesis as well as c-di-GMP-induced stalk gene transcription. (pnas.org)
  • Rho kinase and Ca 2+ entry mediate increased pulmonary and systemic vascular resistance in L-NAME-treated rats," American Journal of Physiology-Lung Cellular and Molecular Physiology , vol. 293, no. 5, pp. (hindawi.com)
  • PKG are serine/threonine kinases that are present in a variety of eukaryotes ranging from the unicellular organism Paramecium to humans. (wikidoc.org)
  • cGMP activates protein kinase G (PKG), which phosphorylates and inhibits GTPase RhoA and decreases Rho-kinase activity. (wikipedia.org)
  • Inactivation of cGKI in mice abolished both NO/cGMP-dependent relaxation of vascular and intestinal smooth muscle and inhibition of platelet aggregation, causing hypertension, intestinal dysmotility, and abnormal hemostasis (13). (diva-portal.org)
  • Endfoot cross‐sectional area was assessed by two‐photon microscopy of mice expressing enhanced green fluorescent protein in astrocytes and related to the degree of arteriolar constriction. (uio.no)
  • These KI mice express a 'trapping mutant' form of Trx that becomes covalently linked to proteins with oxidised thiol after H2O2 or H2S treatment. (bl.uk)
  • The critical role of RhoA/Rho-kinase signaling in various systems is discussed, in particular those vascular smooth muscle disorders involving hypercontractility. (biomedsearch.com)
  • Conclusion- Our work thus defines AMPKα1 as (1) a new kinase for RhoA and (2) a new mediator of the vasoprotective effects of estrogen. (ahajournals.org)
  • 10 RhoA phosphorylation thus appears as a simple physiological mechanism that could be used to control the dynamics of RhoA protein actions and to permit specific limitation or termination of RhoA protein signals. (ahajournals.org)
  • It phosphorylates and activates MEK (MAPK/ERK kinase), which in turn phosphorylates and activates ERK. (asm.org)
  • At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. (jci.org)
  • The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. (bioportfolio.com)
  • Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. (ntu.edu.sg)