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
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 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
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
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 ...
TY - JOUR. T1 - An anti-tumor role for cGMP-dependent protein kinase. AU - Hou, Yali. AU - Gupta, Naren. AU - Schoenlein, Patricia. AU - Wong, Elsie. AU - Martindale, Robert. AU - Ganapathy, Vadivel. AU - Browning, Darren. PY - 2006/8/18. Y1 - 2006/8/18. N2 - This study compared Type-1 cGMP-dependent protein kinase (PKG) expression in normal and tumor tissues and examined PKG function in tumor growth. Studies with a cDNA array revealed that PKG expression was reduced in many tumors compared to respective normal tissue. This decrease in PKG expression was confirmed using quantitative RT-PCR and western blotting of matched colon specimens from normal epithelium and tumor tissue, and also in colon derived cell lines where luciferase reporter analysis revealed that the decreased expression occurred at the transcriptional level. Using SW620 colon carcinoma cells engineered for inducible expression of PKG1β, it was found that exogenous PKG1β lead to decreased tumor growth and invasiveness in nude ...
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
Catalytic domain of the Protein Serine/Threonine Kinase, cGMP-dependent protein kinase. Serine/Threonine Kinases (STKs), cGMP-dependent protein kinase (cGK or PKG) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and ...
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 ...
TY - JOUR. T1 - Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. AU - Potter, Lincoln R.. AU - Abbey-Hosch, Sarah. AU - Dickey, Deborah M.. PY - 2006/2. Y1 - 2006/2. N2 - Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two, NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis ofcGMP.One, NPR-C/NPR3, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. ...
GF ID PRKG1_interact #=GF AC PF15898.5 #=GF DE cGMP-dependent protein kinase interacting domain #=GF AU Eberhardt R;0000-0001-6152-1369 #=GF SE Jackhmmer:A8JNT6 #=GF GA 32.40 32.40; #=GF TC 33.30 32.50; #=GF NC 32.30 32.30; #=GF BM hmmbuild HMM.ann SEED.ann #=GF SM hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq #=GF TP Family #=GF RN [1] #=GF RM 12873707 #=GF RT Dimerization of cGMP-dependent protein kinase 1alpha and the #=GF RT myosin-binding subunit of myosin phosphatase: role of leucine #=GF RT zipper domains. #=GF RA Surks HK, Mendelsohn ME; #=GF RL Cell Signal. 2003;15:937-944. #=GF RN [2] #=GF RM 10567269 #=GF RT Regulation of myosin phosphatase by a specific interaction with #=GF RT cGMP- dependent protein kinase Ialpha. #=GF RA Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, #=GF RA Lincoln TM, Mendelsohn ME; #=GF RL Science. 1999;286:1583-1587. #=GF DR INTERPRO; IPR031775; #=GF DR SO; 0100021; polypeptide_conserved_region; #=GF CC This domain is found at the C-terminus ...
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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 …
Ca2+ is an important intracellular second messenger in signal transduction of endothelial cells. It has long been recognized that a mechanosensitive Ca2+-permeable channel is present in vascular endothelial cells. The activity of this channel may increase intracellular Ca2+ level in endothelial cells. A recent finding is that the activity of this channel may be regulated by cGMP through a protein kinase G-dependent pathway. Inhibition of the channel by cGMP abolishes the Ca2+ influx elicited by flow. Several inhibitors of the cation channel including Gd3+, Ni2+, and SK&F-96365 also inhibit the Ca2+ influx due to flow stimulation. These data suggest that a mechanosensitive cation channel is the primary pathway mediating the flow-induced Ca2+ entry in vascular endothelial cells. Another important finding is that the opening of this mechanosensitive channel by KT5823 leads to endothelium-dependent vascular dilation. Therefore, it appears that this channel may play a crucial role in the regulation of
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 ...
Cyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated intracellular cGMP level exerts its physiological action through two forms of cGMP-dependent protein kinase (PKG), cGMP-regulated phosphodiesterases (PDE2, PDE3) and cGMP-gated cation channels, among which PKGs might be the primary mediator. PKG1 isoform-specific activation of established substrates leads to reduction of cytosolic calcium concentration and/or decrease in the sensitivity of myofilaments to Ca2+ (Ca2+-desensitization), resulting in smooth muscle relaxation. In cardiac myocyte, PKG directly phosphorylates a member of the transient potential receptor canonical channel family, TRPC6, suppressing this nonselective ion channels Ca2+ conductance, G-alpha-q agonist-induced NFAT activation, and myocyte hypertrophic responses. PKG also opens mitochondrial ATP-sensitive K+ (mitoKATP) channels ...
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 ...
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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 ...
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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 ...
Dive into the research topics of Protein kinase G positively regulates proteasome-mediated degradation of misfolded proteins. Together they form a unique fingerprint. ...
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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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For the parsing of the commands and files, some limitations on package names are required. This will limit what pkg commands can do. For example, if a package name is allowed to use a hyphen, then commands such as pkg load image-2.0.0 can no longer be used to load a specific package version. Something such as pkg load image::2.0.0 would have to be used. Using this alternative syntax means that package names cannot have colons. This is not only limited to package versions. As pkg is to be expanded to load pkg databases from other files (packages in a not always mounted directory for example), it becomes a possibility to have more than one package with the same version available to pkg load. This means that it becomes necessary to specify which package to load. Something like pkg load image-lab-2.0.0 can be used. A nice thing would also be pkg load image-2.0.0 from lab but that would add one of following 2 limitations: either no package can be named from; or pkg load becomes limited to ...
Author: behdad Update of /cvs/pkgs/rpms/pango/devel In directory 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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"Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype". Journal of Vascular Research. 34 (4): 245 ... Lincoln, T. M.; Cornwell, Taylor (March 1990). "cGMP-dependent protein kinase mediates the reduction of Ca2+ by cAMP in ... increased cGMP triggers an increase in protein kinase G (PKG) activity. PKG reduces intracellular Ca2+ in vascular smooth ... "Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent ...
A Purkinje cell substrate of the cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 274 (6): 3485-95. ... a possible downstream component of the cGMP-dependent protein kinase cascade in cerebellar Purkinje cells". Proceedings of the ... Hall KU, Collins SP, Gamm DM, Massa E, DePaoli-Roach AA, Uhler MD (Feb 1999). "Phosphorylation-dependent inhibition of protein ... Protein phosphatase 1 regulatory subunit 17 is a protein that in humans is encoded by the PPP1R17 gene. GRCh38: Ensembl release ...
5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. doi: ... Hirota J, Ando H, Hamada K, Mikoshiba K (Jun 2003). "Carbonic anhydrase-related protein is a novel binding protein for inositol ... ITPR1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) GeneReviews/NCBI/NIH/UW entry on ... Inositol 1,4,5-trisphosphate receptor type 1 is a protein that in humans is encoded by the ITPR1 gene. ITPR1 has been shown to ...
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 ...
"The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading". J. ... "Protein phosphorylation regulated by cyclic nucleotide-dependent protein kinases in cell extracts and in intact human ... 2000). "KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial ... VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. Vasodilator-stimulated phosphoprotein has been shown ...
"Localization of the human gene for the type I cyclic GMP-dependent protein kinase to chromosome 10". Cytogenetics and Cell ... of a novel male germ cell-specific cGMP-dependent protein kinase-anchoring protein by cGMP-dependent protein kinase Ialpha". ... 5-trisphosphate receptor by cyclic GMP-dependent protein kinase". The Journal of Biological Chemistry. 269 (12): 8701-7. doi: ... cGMP-dependent protein kinase 1, alpha isozyme is an enzyme that in humans is encoded by the PRKG1 gene. PRKG1 has been shown ...
EC Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System cGMP-Dependent+Protein+Kinases at the US ... cGMP-dependent protein kinase or protein kinase G (PKG) is a serine/threonine-specific protein kinase that is activated by cGMP ... "A crystal structure of the cyclic GMP-dependent protein kinase I{beta} dimerization/docking domain reveals molecular details of ... April 2008). "Expression of cyclic guanosine monophosphate-dependent protein kinase in metastatic colon carcinoma cells blocks ...
... is a cyclic GMP-dependent protein kinase I-binding protein and substrate in vascular smooth muscle cells". The Journal of ... FH1/FH2 domain-containing protein 1 is a protein that in humans is encoded by the FHOD1 gene. This gene encodes a protein which ... The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. ... It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. FHOD1 has been shown to interact ...
This in turn leads to increased cAMP-dependent protein kinase or PKA (protein kinase A) activity, ultimately promoting ... Nitric oxide and cyclic GMP in cell signaling and drug development". The New England Journal of Medicine. 355 (19): 2003-11. ... The cGMP then activates cGMP-dependent kinase or PKG (protein kinase G). Activated PKG promotes vasorelaxation (via a reduction ... Francis SH, Busch JL, Corbin JD, Sibley D (2010). "cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide ...
Cyclic GMP binds to the cGMP-dependent protein kinase (PKG1) which phosphorylates several proteins that results in decreased ... cGMP binding proteins and protein kinase G (PKG). The effect on PKG reduces levels of calcium leading to relaxation of smooth ... Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine ... PDEs are enzymes that hydrolyze cyclic adenosine 3,5-monophosphate (cAMP) and cyclic guanosine 3,5-monophospahate (cGMP), which ...
Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal potentiation and pain ... Yinhe Hu, he further discovered that soluble guanylyl clcyaes (sGC) and cGMP-dependent protein kinase (PKG) act downstream from ... 10;74(3):517-29 Saywell SA, Babiec WE, Neverova NV, Feldman JL (2010) Protein kinase G-dependent mechanisms modulate ... Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Nature 368, 635-639. Zhuo, M., Hu, Y., ...
... inducing a signaling cascade that results in the activation of cGMP-dependent protein kinase (PKG) and an ultimate decrease in ... In addition to this, it has already been shown that NO stimulates increased cyclic GMP (cGMP) levels in the smooth muscle cells ... When these proteins are active, they turn on SREBP2 which inhibits LRP-1. LRP-1 helps the brain remove amyloid beta. Therefore ... Two proteins are involved in this accumulation of amyloid beta: serum response factor or SRF and myocardin. Together, these 2 ...
... cyclic gmp-dependent protein kinases MeSH D12.644.360.200.575 - protamine kinase MeSH D12.644.360.250 - cyclin-dependent ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 - map kinase kinase kinase 2 MeSH D12.644.360.400.300 - map kinase kinase ... cyclic nucleotide-regulated protein kinases MeSH D12.644.360.200.125 - cyclic amp-dependent protein kinases MeSH D12.644. ... kinase 3 MeSH D12.644.360.400.400 - map kinase kinase kinase 4 MeSH D12.644.360.400.500 - map kinase kinase kinase 5 MeSH ...
... where it stimulates a protein kinase called cyclic AMP-dependent protein kinase. By phosphorylating proteins, cyclic AMP- ... G proteins). The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) ... Eckly-Michel A, Martin V, Lugnier C (September 1997). "Involvement of cyclic nucleotide-dependent protein kinases in cyclic AMP ... Wolter S, Golombek M, Seifert R (December 2011). "Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic ...
cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein kinase G) is a dimer consisting ... Numerous cyclic nucleotide phosphodiesterases (PDE) can degrade cGMP by hydrolyzing cGMP into 5'-GMP. PDE 5, -6 and -9 are cGMP ... cyclic monophosphate (8-Br-cGMP) Francis SH, Corbin JD (August 1999). "Cyclic nucleotide-dependent protein kinases: ... Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory ...
It acts as an activator of cGMP-dependent protein kinases. 8-Bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) Rapoport, RM ... "Sodium nitroprusside-induced protein phosphorylation in intact rat aorta is mimicked by 8-bromo cyclic GMP" (Free full text). ... 8-Bromoguanosine 3′,5′-cyclic monophosphate is a brominated derivative of cyclic guanosine monophosphate (cGMP). ... 8-Bromoguanosine-3′,5′-cyclic monophosphate ( 8-Br-cGMP ) (Chemical articles with multiple compound IDs, Multiple chemicals in ...
Then, it converts adenosine triphosphate into cyclic AMP, which activates Protein kinase A. PKA leads to protein tyrosine ... "Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes". Biology of ... These proteins activate protein tyrosine kinase (PTK) that phosphorylates various proteins important for capacitation and ... Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase) regulates gene transcription through successive kinase ...
"Synergism between calcium and cyclic GMP in cyclic AMP response element-dependent transcriptional regulation requires ... Shimomura A, Ogawa Y, Kitani T, Fujisawa H, Hagiwara M (Jul 1996). "Calmodulin-dependent protein kinase II potentiates ... The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal ... This protein is a CREB transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This protein ...
Cyclic-GMP activates protein kinase G, which causes reuptake of Ca2+ and the opening of calcium-activated potassium channels. ... The neuronal enzyme (NOS-1) and the endothelial isoform (NOS-3) are calcium-dependent and produce low levels of this gas as a ... Hemoglobin is a prominent example of a heme protein that may be modified by NO by both direct attack by NO and, independently, ... The iron-containing proteins ribonucleotide reductase and aconitase are deactivated by NO. NO has been demonstrated to activate ...
The molecular mechanism of smooth muscle relaxation involves the enzyme CGMP-dependent protein kinase, also known as PKG. This ... June 1996). "Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile ... Francis SH, Busch JL, Corbin JD, Sibley D (September 2010). "cGMP-dependent protein kinases and cGMP phosphodiesterases in ... Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in ...
"Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation". ... Roskoski R, Roskoski LM (Jan 1987). "Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second ... that are phosphorylated by a variety of protein kinases. Ser40 is phosphorylated by the cAMP-dependent protein kinase. Ser19 ( ... is phosphorylated by the calcium-calmodulin-dependent protein kinase. MAPKAPK2 (mitogen-activated-protein kinase-activating ...
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. ...
... which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes ... "Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent ... mitogen-activated protein kinase, PPAR gamma, HIF1A, NRF2, ion channels, cystathionine beta synthase, and numerous other ... ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron regulatory factor activation. NO has been ...
CNG channel activity is controlled by the interaction between cGMP-dependent protein kinase and G1 protein because of cGMP's ... "Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment". Nature. 313 (6000): 310-3. ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ... Cyclic nucleotide-gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic ...
... beta-adrenergic-receptor kinase MeSH D08.811.913.696.620.682.700.150.150 - cyclic gmp-dependent protein kinases MeSH D08.811. ... cyclic nucleotide-regulated protein kinases MeSH D08.811.913.696.620.682.700.150.125 - cyclic amp-dependent protein kinases ... map kinase kinase kinase 1 MeSH D08.811.913.696.620.682.700.559.200 - map kinase kinase kinase 2 MeSH D08.811.913.696.620.682. ... map kinase kinase kinase 3 MeSH D08.811.913.696.620.682.700.559.400 - map kinase kinase kinase 4 MeSH D08.811.913.696.620.682. ...
... which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A (PKA) and Ca2+ ... and cyclic GMP (cGMP) levels fall in vascular smooth muscle. This impairs relaxation in the vasculature and is a part of the ... In myocytes, the increase of cAMP concentration increases in turn the activity of PKA; this kinase improves the Ca2+ inward ... calmodulin kinase pathways. Increases cardiac contractility, vasodilator. Acts by inhibiting the breakdown of both cAMP and ...
cGMP-dependent 3',5'-cyclic phosphodiesterase is an enzyme that in humans is encoded by the PDE2A gene. GRCh38: Ensembl release ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... Sadhu K, Hensley K, Florio VA, Wolda SL (1999). "Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A ... 2009). "Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability". Blood ...
The synthesised cGMP acts as a secondary messenger and activates cGMP-dependent protein kinase (protein kinase G) to regulate ... reducing cyclic GMP degradation. Endothelin receptor antagonist, another class of drugs used in PAH Riociguat FDA Professional ... Riociguat at concentration between 0.1 and 100 μM stimulates in a dose-dependent manner sGC activity up to 73-fold. In addition ... NO binds to soluble guanylate cyclase (sGC) and mediates the synthesis of the secondary messenger cyclic guanosine ...
Weel/Mtyl inhibits cell division cycle 25B (CDC25B) which is a main activator for Cyclin-dependent kinase (CDK). This leads to ... "Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles". ... Inhibition of Gs protein in mouse oocyte leads to meiotic resumption. Gs protein-coupled receptor 3 (GPCR3) KO mice was found ... Roles of Mitogen-Activated Protein Kinase". Molecular Endocrinology. 21 (9): 2037-2055. doi:10.1210/me.2006-0408. ISSN 0888- ...
"A Cyclic GMP-Dependent K + Channel in the Blastocladiomycete Fungus Blastocladiella emersonii". Eukaryotic Cell. 14 (9): 958- ... Histidine kinases in fungi are hybrid histidine kinases due to the fusion of histidine kinase/histidine kinase-like ATPase ... Other fluorescent proteins, including tdTomato, mClover3, mCitrine, and mCerulean3, are functional in S. punctatus. A high- ... Type 2 opsins belong to Class A family of G-protein coupled receptors. Both types are seven-transmembrane receptors and bind ...
... cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor". Growth Factors. 19 (3): 193-206. doi: ... There are three isoforms of this protein: PGF-1, PGF-2, PGF-3. PGF-1 is specifically found in the colon as well as mammary ... Serum levels of PGF and sFlt-1 (soluble fms-like tyrosine kinase-1, also known as soluble VEGF receptor-1) are altered in women ... Shibuya M (April 2008). "Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis". BMB Reports ...
... cGMP-dependent protein kinase I alpha and beta, and cyclic nucleotide-gated channel subunit 1 in the rat testis". Journal of ... "Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel". Nature. ... Cyclic nucleotide-gated channel alpha 1, also known as CNGA1, is a human gene encoding an ion channel protein. Heterologously ... Chen, T.-Y.; Peng, Y.-W.; Dhallan, R. S.; Ahamed, B.; Reed, R. R.; Yau, K.-W. (April 1993). "A new subunit of the cyclic ...
"Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning". Nature. 423 (6943): 990-5 ... DCC and UNC-5 proteins mediate netrin-1 responses. The UNC-5 protein is mainly involved in signaling repulsion. DCC, which is ... In the first pathway, the focal adhesion kinase (FAK) is bound to DCC and both undergo tyrosine phosphorylation upon netrin-1 ... Netrins 1, 3, and 4 are secreted proteins, whereas G1 and G2 are membrane bound proteins tethered by Glycophosphatidylinositol ...
... through a protein kinase C-dependent mechanism". Biochem J. 466 (2): 379-90. doi:10.1042/bj20140881. PMID 25422863. Milo, Ron; ... Pugh, E. N. Jr.; Lamb, T. D. (1990). "Cyclic GMP and calcium: The internal messengers of excitation and adaptation in ... Calcium coordination plays an important role in defining the structure and function of proteins. An example a protein with ... Ca2+ ion can also determine the speed of adaptation in a neural system depending on the receptors and proteins that have varied ...
... cyclic di-GMP). Degradation of cyclic di-GMP to guanosine monophosphate (GMP) is catalyzed by a phosphodiesterase (PDE). ... Often, GGDEF domains with DGC activity are found in the same proteins as c-di-GMP-specific phosphodiesterase (PDE) EAL (Glu-Ala ... Paul R, Weiser S, Amiot NC, Chan C, Schirmer T, Giese B, Jenal U (March 2004). "Cell cycle-dependent dynamic localization of a ... In enzymology, diguanylate cyclase, also known as diguanylate kinase (EC, is an enzyme that catalyzes the chemical ...
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 ...
IkB kinase EC cAMP-dependent protein kinase EC cGMP-dependent protein kinase EC protein kinase ... cyclic GMP-AMP synthase The remaining entries have no Wikipedia articles EC L- synthase EC GDP ... mitogen-activated protein kinase EC mitogen-activated protein kinase kinase kinase EC tau-protein kinase ... mitogen-activated protein kinase kinase EC protein-histidine pros-kinase EC protein-histidine tele-kinase ...
CEF scientists showed that GABARAP proteins are not only involved in autophagy but also in the ubiquitin-dependent degradation ... or for the manipulation of cyclic GMP. Several CEF groups joined forces not only to unravel the photocycle of ChR2 at different ... "The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures". Leukemia. 25 (1): ... light-dependent RNA interference and light-dependent transcription were realized. Wavelength-selective light-triggering was ...
Second, it serves as an adaptor protein to aid the receptor to the clathrin-dependent endocytosis machinery (to induce receptor ... As rhodopsin is phosphorylated by rhodopsin kinase (a member of the GPCR kinases(GRKs)), it binds with high affinity to the ... GMP. Reduction in cGMP allows the ion channels to close, preventing the influx of positive ions, hyperpolarizing the cell, and ... cells have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which opens ion channels (largely ...
Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase ... can manifest as a deletion or truncation in the final protein. Splicing is catalyzed by the spliceosome, a large RNA-protein ... NAD-dependent 2'-phosphotransferase then removes the 2'-phosphate group. Splicing occurs in all the kingdoms or domains of life ... GMP, GDP, GTP) attacks phosphate at the 5' splice site. 3'OH of the 5' exon becomes a nucleophile and the second ...
Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools in ... Our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, Plasmodium falciparum ... Cyclic GMP-Dependent Protein Kinases / genetics * Cyclic GMP-Dependent Protein Kinases / metabolism* ... Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools in ...
Phosphorylation of proteins is an essential signalling mechanism in eukaryotic and prokaryotic cells. Although N- ... 31 Glass, D. B. (1983) Differential responses of cyclic. GMP-dependent and cyclic AMP-dependent protein kinases to ... A protein kinase was purified from rat liver nuclei by affinity chromatography on poly(l-lysine)-agarose and protein kinase ... tional lysine kinase activity [18], protein lysine kinases involved. in histone H1 phosphorylation [19] and bovine liver ...
PRKG1 codes for the cyclic GMP-dependent protein kinase I (PKGI). Activation of PKGI leads to the inhibition of RhoA and Rho- ... associated kinases (ROCK). Hence, variation in PRKG1 expression is expected to modify the activity of the RhoA-ROCK pathway. ...
Cyclic GMP-Dependent Protein Kinases 100% * Pulmonary Artery 69% * Nitric Oxide 61% ... Prolonged treatment of porcine pulmonary artery with nitric oxide decreases cGMP sensitivity and cGMP-dependent protein kinase ...
Fiscus RR, Rapoport RM, Waldman SA, Murad F. Atriopeptin II elevates cyclic GMP, activates cyclic GMP-dependent protein kinase ... Endothelium-dependent and nitrovasodilator-induced activation of cyclic GMP-dependent protein kinase in rat aorta. J Cyclic ... Cyclic GMP/protein kinase G type-Iα (PKG-Iα) signaling pathway promotes CREB phosphorylation and maintains higher c-IAP1, livin ... Involvement of cyclic GMP and protein kinase G in the regulation of apoptosis and survival in neural cells. Neurosignals. 2002 ...
Predictions of cyclic GMP-dependent protein kinase structure from its primary sequence. ... Using the structural alignment of channel-kinase TRPM7/ChaK1 with cyclic-AMP dependent kinase, the consensus motifs of alpha- ... They include elongation factor 2 kinase, Dictyostelium myosin heavy chain kinases and many other protein kinases from diverse ... A comparison of the sequences of the mammalian and Dictyostelium catalytic subunits of cAMP-dependent protein kinase revealed ...
Activator of cGMP-dependent protein kinases I α, I β & type II and cGMP-gated ion channels (cyclic GMP agonist). Increased ... "Activation of Mitogen-Activated Protein Kinase Pathways by Cyclic GMP and Cyclic GMP-Dependent Protein Kinase in Contractile ... Chem., 274, 8391 - 8404 (1999), "Cyclic AMP- and Cyclic GMP-Dependent Protein Kinases Differ in Their Regulation of Cyclic AMP ... Biol., 18, 6983 - 6994 (1998), "Cyclic-GMP-Dependent Protein Kinase Inhibits the Ras/Mitogen-Activated Protein Kinase Pathway" ...
Cyclic GMP-Dependent Protein Kinases 100% * Plasmodium falciparum 79% * Isoxazoles 72% * 4-(2-(4-fluorophenyl)-5-(1- ... Characterization of Competitive Inhibitors of Plasmodium falciparum cGMP-Dependent Protein Kinase**. Eck, T., Laureano de Souza ...
Protein Phosphatase 2 32% * Phosphorylation 17% * Cyclic GMP-Dependent Protein Kinases 16% ... VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMP-dependent pathway. Mayhan, W. G., 1999 ... Alfin1, a novel zinc-finger protein in alfalfa roots that binds to promoter elements in the salt-inducible MsPRP2 gene. Bastola ... Association of malondialdehyde-acetaldehyde (MAA) adducted proteins with atherosclerotic-induced vascular inflammatory injury. ...
Cyclic GMP Dependent Protein Kinase Cyclic GMP Dependent Protein Kinases Cyclic GMP-Dependent Protein Kinase G Kinase G Kinases ... Cyclic GMP Dependent Protein Kinase. Cyclic GMP Dependent Protein Kinases. Cyclic GMP-Dependent Protein Kinase. G Kinase. G ... Kinase, cGMP-Dependent Protein Kinases, cGMP-Dependent Protein Protein Kinase G Protein Kinase, cGMP-Dependent Protein Kinases ... cGMP Dependent Protein Kinase cGMP Dependent Protein Kinases cGMP-Dependent Protein Kinase cGMP-Dependent Protein Kinases ...
Cyclic GMP-Dependent Protein Kinases Medicine & Life Sciences 83% * Peptide Receptors Medicine & Life Sciences 78% ... Atrial natriuretic peptide induces natriuretic peptide receptor-cGMP-dependent protein kinase interaction. In: Journal of ... Dive into the research topics of Atrial natriuretic peptide induces natriuretic peptide receptor-cGMP-dependent protein kinase ... Atrial natriuretic peptide induces natriuretic peptide receptor-cGMP-dependent protein kinase interaction. Journal of ...
Cyclic GMP-Dependent Protein Kinases Medicine & Life Sciences 31% View full fingerprint ... We have found that guanosine 3′,5′-monophosphate (cGMP) - dependent protein kinase (PKG) functions directly as a redox sensor. ... We have found that guanosine 3′,5′-monophosphate (cGMP) - dependent protein kinase (PKG) functions directly as a redox sensor. ... We have found that guanosine 3′,5′-monophosphate (cGMP) - dependent protein kinase (PKG) functions directly as a redox sensor. ...
... it has not been reported whether resveratrol has effects on cyclic-GMP-dependent protein kinase (protein kinase G, PKG), a ... Involvement of cyclic GMP and protein kinase G in the regulation of apoptosis and survival in neural cells. Neurosignals 11: ... Cyclic GMP/protein kinase G type-Ialpha (PKG-Ialpha) signaling pathway promotes CREB phosphorylation and maintains higher c- ... Expression of cGMP-dependent protein kinase I and phosphorylation of its substrate, vasodilator-stimulated phosphoprotein, in ...
Ca(2+)-Calmodulin Dependent Protein Kinase. Calcium-Calmodulin-Dependent Protein Kinases. Cholesterol Esterase. Sterol Esterase ... Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... SHP1 Protein Tyrosine Phosphatase. Protein Tyrosine Phosphatase, Non-Receptor Type 6. Thioredoxin Reductase (NADPH). ... Protein Isoprenylation. Protein Prenylation. G09 - Circulatory and Respiratory Physiology. Hemodynamic Processes. Hemodynamics ...
... calcium/calmodulin-dependent protein kinase II; CCL7: chemokine (C-C motif) ligand 7; CGAS: cyclic GMP-AMP synthase; CQ: ... mitogen-activated protein kinase; MAPK1/ERK: mitogen-activated protein kinase 1; MMP2: matrix metallopeptidase 2; MAPK8/JNK: ... mitogen-activated protein kinase 8; MAPK14/p38: mitogen-activated protein kinase 14; NFE2L2/NRF2: nuclear factor, erythroid ... to K63 ubiquitinated protein, and increasing the levels of p-MAPK8/JNK (mitogen-activated protein kinase 8) and nuclear factor ...
Cyclic GMP-Dependent Protein Kinases Medicine & Life Sciences 100% * Adrenergic Agents Medicine & Life Sciences 73% ... G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing ... N2 - G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, ... AB - G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, ...
Cyclic gmp-dependent protein kinase pathway underlying smooth muscle, depression.. *is lexapro the strongest antidepressent ... Cyclic gmp, high-yield videos and reports prepared to speak with flashcards need of all drugs purchased as citrate is? Begin to ...
Lack of association between polymorphism of the human cyclic GMP-dependent protein kinase gene and obesity. International ...
... to activate protein kinase G, with PDE5-I regulating nitric oxide (NO) and PDE9-I natriuretic peptide-dependent signaling. ... posttranscriptionally regulate mRNA and its translation into protein, and are considered master controllers of genes modulating ... Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-induced PDE5 phosphorylation. ... to activate protein kinase G, with PDE5-I regulating nitric oxide (NO) and PDE9-I natriuretic peptide-dependent signaling. ...
Deschatrettes E, Jouvert P, Zwiller J. Overexpression of cyclic GMP-dependent protein kinase reduces MeCP2 and HDAC2 expression ... CNP, but not ANP or BNP, relax human isolated subcutaneous resistance arteries by an action involving cyclic GMP and BKCa ... ENaC is regulated by natriuretic peptide receptor-dependent cGMP signaling. Am J Physiol Renal Physiol. 2013;304(7):F930-F937. ... C-type natriuretic peptide inhibiting vascular calcification might involve decreasing bone morphogenic protein 2 and ...
... encoding cGMP-dependent protein kinase II) and Npr3 (natriuretic peptide decoy receptor) genes. Conversely, DEX was found to ... Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification. ... encoding cGMP-dependent protein kinase I, A) and Prkg2 (encoding cGMP-dependent protein kinase II, B) mRNA levels were ... and cGMP-dependent protein kinases cGKI and cGKII (Prkg1, Prkg2, respectively) [9, 16]. A third type of natriuretic peptide ...
Cyclic GMP can directly stimulate If but it is ∼10-fold less potent than the physiological If-gating nucleotide, cAMP. In ... Aim: To elucidate the role of PDE3, PKA and PKG in mediating the NO-If-dependent increase in HR. Methods and Results: In ... the present findings provide an important link between the activation of GC with NO donors and the NO-dependent mobilization of ... ventricular myocytes, NO can increase cAMP levels through a cGMP-dependent inhibition of PDE3. ...
We identified various protein kinases as cCMP-binding proteins in tissue lysates. cCMP stimulated cyclic GMP-dependent protein ... Then we investigated the effect of cCMP on purified cyclic nucleotide-dependent protein kinases and on intact tissues of ... We confirmed that cCMP activates the purified cyclic nucleotide-dependent protein kinases cAK and cGK. ... cyclic AMP or 3:5- cyclic GMP. J Biol Chem. 1978, 253: 2522-2524. ...
... in vivo phosphorylation of thromboxane receptor by cyclic GMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1998 Apr 28; ... Endotoxin-induced arachidonic acid metabolism requires de novo protein synthesis and protein kinase C activation. Biochim ... Involvement of G(i) proteins and Src tyrosine kinase in TNFalpha production induced by lipopolysaccharide, group B Streptococci ... Implication of Galpha i proteins and Src tyrosine kinases in endotoxin-induced signal transduction events and mediator ...
... including a cyclic GMP signaling pathway involving nitric oxide synthase, guanylyl cyclase, and cGMP-dependent protein kinase ( ... rather it initiates a kinase cascade that leads to SERT phosphorylation by an as yet unidentified protein kinase (Wong et al., ... Sodium dependent serotonin transporter antibody, Sodium-dependent serotonin transporter antibody, Solute carrier family 6 ( ... Western blot of rat mid brain membrane lysate showing specific immunolabeling of the ~76 kDa SERT protein phosphorylated at ...
Depletion of cyclic-GMP levels and inhibition of cGMP-dependent protein kinase activate p21Cip1 /p27Kip1 pathways and lead to ... Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Lincoln R Potter, ...
... and it also causes endothelium-dependent relaxations in isolated small mesenteric arteries. KT-5823-induced relaxations in ... The activity of the channel is increased by KT-5823, a highly selective inhibitor of protein kinase G (PKG), while it is ... Acetylcholine, Alkaloids, Animals, Biological Factors, Calcium, Carbazoles, Cations, Cyclic GMP-Dependent Protein Kinases, ... Endothelial cell protein kinase G inhibits release of EDHF through a PKG-sensitive cation channel. ...
It activates cyclic GMP -dependent protein kinase G . The activated PKG can directly phosphorylate and potentially turns on ... dependent protein kinase C phosphorylation regulating Focal adhesion kinase /paxillin-mediated cell division cycle 42 /actin- ... How Does A Man 66 With Insulin Dependent Diabetes Retire And Afford Medicine. Can Melatonin Lower Blood Sugar Therefore, we ... cGMP signaling cascade also target on cyclic nucleotide-gated channels and cGMP-specific phosphodiesterases . ...
... through a cyclic gmp dependent protein kinase. reduced availability of phosphorylated (active) mlck interferes with activation ... through a cyclic gmp dependent protein kinase. reduced availability of phosphorylated (active) mlck interferes with activation ... elevated levels of cyclic gmp also reduce calcium entry which also contributing to relaxation. it dilates veins more than ... elevated levels of cyclic gmp also reduce calcium entry which also contributing to relaxation. it dilates veins more than ...
Ca(2+)-Calmodulin Dependent Protein Kinase. Calcium-Calmodulin-Dependent Protein Kinases. Cholesterol Esterase. Sterol Esterase ... Cyclic-GMP Phosphodiesterase. 3,5-Cyclic-GMP Phosphodiesterases. 3,5-Cyclic-Nucleotide Phosphodiesterase. 3,5-Cyclic-AMP ... SHP1 Protein Tyrosine Phosphatase. Protein Tyrosine Phosphatase, Non-Receptor Type 6. Thioredoxin Reductase (NADPH). ... Protein Isoprenylation. Protein Prenylation. G09 - Circulatory and Respiratory Physiology. Hemodynamic Processes. Hemodynamics ...
  • Our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, Plasmodium falciparum, remains rudimentary. (
  • By employing chemical and genetic tools in combination with quantitative global phosphoproteomics, we identify the phosphorylation sites on 69 proteins that are direct or indirect cellular targets for PfPKG. (
  • Phosphorylation of proteins is an essential signalling mechanism in eukaryotic and prokaryotic cells. (
  • A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins. (
  • Phosphorylation of the receptor by an unknown serine/threonine kinase is required before ligand binding can activate the cyclase. (
  • Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-induced PDE5 phosphorylation. (
  • cCMP stimulated cyclic GMP-dependent protein kinases in WT tissue lysates, however there was no stimulation of phosphorylation in KO tissue lysates. (
  • 2007). It has been suggested that although PKG is involved in the stimulation of SERT at Thr-276, it does not directly phosphorylate the residue, rather it initiates a kinase cascade that leads to SERT phosphorylation by an as yet unidentified protein kinase (Wong et al. (
  • Inhibition of PDE2 acted by diminishing the Ca 2+ dependent reduction of mitochondrial cAMP, thereby promoting NCLX phosphorylation. (
  • The phosphorylation of MEK-2 increased in the presence of 10(-4) M dibutyryl cyclic AMP (twofold), 1 mM methylisobutylxanthine (2.5-fold), 10(-5) M isoproterenol (fivefold), and 10(-9) M cholera toxin (sevenfold). (
  • Neither cyclic GMP, Ca++, hydrocortisone, nor epidermal growth factor had any effect on the phosphorylation of MEK-1 or MEK-2. (
  • The results indicate that the phosphorylation of these two keratins is independently controlled by cyclic AMP-dependent kinase for MEK-2 and by cyclic nucleotide-independent kinase for MEK-1. (
  • The binding of IQ 1 to PR72/130 leads to decreased phosphorylation of the coactivator protein p300 at Ser-89. (
  • Cheng YC, Bloch A: Demonstration, in leukemia L-1210 cells, of a phosphodiesterase acting on 3':5'-cyclic CMP but not on 3':5'-cyclic AMP or 3':5'- cyclic GMP. (
  • His studies deal with areas such as Protein kinase A, Pharmacology and Cyclic nucleotide as well as Phosphodiesterase. (
  • He focuses mostly in the field of Pathological, narrowing it down to topics relating to Cyclic nucleotide phosphodiesterase and, in certain cases, Bioinformatics, Second messenger system, Intracellular, Cause of death and Cardiac hypertrophy. (
  • He interconnects Nucleotide, Cyclic nucleotide phosphodiesterases, Cause of death and Cyclic nucleotide phosphodiesterase in the investigation of issues within Heart failure. (
  • Activation of intestinal CFTR Cl‐ channel by heat‐stable enterotoxin and guanylin via cAMP‐dependent protein kinase. (
  • SERT is regulated by several processes, including a cyclic GMP signaling pathway involving nitric oxide synthase, guanylyl cyclase, and cGMP-dependent protein kinase (PKG). (
  • it is enzymatically denitrated in the smooth muscle cells to release the reactive free radical nitric oxide which activates cytosolic guanylyl cyclase thus increases cyclic gmp levels which causes dephosphorylation of myosin light chain kinase(mlck) through a cyclic gmp dependent protein kinase. (
  • 2004. An evolutionarily conserved mechanism for sensitization of soluble guanylyl cyclase reveals extensive nitric oxide-mediated upregulation of cyclic GMP in insect brain. (
  • Lucas K. A., Pitari G. M., Kazerounian S., Ruiz-Stewart I., Park J., Schulz S., Chepenik K. P., Waldman S. A. Guanylyl ceclases and signaling by cyclic GMP // Pharmacological reviews. (
  • kinase homology domain of ANPRA (guanylyl cyclase-A) activates downstream targets of ANP/ANPR signaling. (
  • However, the role of downstream cGMP/protein kinase G (PKG) signaling, a pathway activated by NO/eNOS, in pro- and anti-angiogenic effects of resveratrol is still unclear. (
  • Materials and Methods: Endogenous NO/cGMP/PKG pathway and downstream cell-survival proteins (Inhibitor of Apoptosis Proteins, IAPs) were studied in relation to pro- and anti-angiogenic effects of resveratrol in human umbilical vein endothelial cells (HUVECs). (
  • Cyclic guanosine monophosphate (cGMP) and its downstream effector cGMP kinase I (cGKI) have been suggested to be an important anti-hypertrophic signalling pathway (1). (
  • Activation of a COI1-dependent pathway in Arabidopsis by Pseudomonas syringae type III effectors and coronatine. (
  • We have found that guanosine 3′,5′-monophosphate (cGMP) - dependent protein kinase (PKG) functions directly as a redox sensor. (
  • Both inhibitors augment cyclic guanosine monophosphate (cGMP) to activate protein kinase G, with PDE5-I regulating nitric oxide (NO) and PDE9-I natriuretic peptide-dependent signaling. (
  • Cyclic nucleotide phosphodiesterases comprise an 11-member superfamily yielding near 100 isoform variants that hydrolyze cAMP or cGMP to their respective 5'-monophosphate form. (
  • Formation of the cyclic pyrimidine nucleotide cyclic cytidine 3',5'-monophosphate (cCMP) by cytidylyl cyclases is debated. (
  • Ervens J, Seifert R: Differential modulation by N4, 2'-O-dibutyryl cytidine 3':5'-cyclic monophosphate of neutrophil activation. (
  • Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. (
  • Influence of the endothelium is modeled as the increase of nitric oxide (NO) concentration and subsequent production of cyclic quanosine monophosphate (cGMP). (
  • Conclusion: Resveratrol-induced anti-angiogenesis/pro-apoptosis induced suppression of PKG signaling and decreased expression of the cell-survival proteins c-IAP1, c-IAP2, livin and XIAP. (
  • G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways. (
  • Lincoln T. M., Dey N., Sellak H. cGMP-dependent protein kinase signaling mechanisms in smooth muscle : from the regulation of tone to gene expression // J. Appl. (
  • [ 43 ] Moreover, TRIF-dependent responses are crucial for host defense against systemic E. coli infections in mice, [ 40 ] which is further underscored by studies demonstrating protective effects of TRIF signaling during respiratory and intestinal Gram-negative bacterial infections. (
  • These PfPKG targets include proteins involved in cell signalling, proteolysis, gene regulation, protein export and ion and protein transport, indicating that cGMP/PfPKG acts as a signalling hub that plays a central role in a number of core parasite processes. (
  • Mechanism of regulation of receptor histidine kinases. (
  • 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. (
  • Activation of PKGI leads to the inhibition of RhoA and Rho-associated kinases (ROCK). (
  • In ventricular myocytes, NO can increase cAMP levels through a cGMP-dependent inhibition of PDE3. (
  • We found that protection of neurons against excitotoxic insults, conferred by PDE2 inhibition, was diminished in NCLX KO neurons, thus is NCLX dependent. (
  • Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. (
  • Activator of cGMP-dependent protein kinases I α, I β & type II and cGMP-gated ion channels (cyclic GMP agonist). (
  • Circulating natriuretic peptides such as atrial natriuretic peptide (ANP) counterbalance the effects of hypertension and inhibit cardiac hypertrophy by activating cGMP-dependent protein kinase (PKG). (
  • In addition, DEX stimulates expression of Prkg2 (encoding cGMP-dependent protein kinase II) and Npr3 (natriuretic peptide decoy receptor) genes. (
  • Lukowski R, Rybalkin SD, Loga F, Leiss V, Beavo JA, Hofmann F: Cardiac hypertrophyis not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes. (
  • These purine cyclic nucleotides activate PKA and PKG, respectively. (
  • So far, there was no evidence of further cyclic nucleotides acting as second messengers. (
  • However, it has not been reported whether resveratrol has effects on cyclic-GMP-dependent protein kinase (protein kinase G, PKG), a biologically- and clinically-important serine/threonine-kinase mediating many physiological and pharmacological effects of nitric oxide (NO), an important pro-angiogenic factor, or on downstream proteins regulated by PKG. (
  • XIV" YNL224C 2 15 16 YNL224C "Ynl224cp,XIV" YNL238W 2 15 17 YNL238W "Ca2+-dependent serine protease,XIV" YNL240C 2 15 18 YNL240C "Nar1p,XIV" YNL242W 2 15 19 YNL242W "Required for sporulation. (
  • His Heart failure research integrates issues from PDE1, Cyclic nucleotide phosphodiesterases, Contractility and Nucleotide. (
  • Basidiocarps of A. hygrometricus are rich in proteins, carbohydrates, minerals, crude fibre and essential amino acids with lower concentration of fat. (
  • Basidiocarp of this macrofungi contains considerable amount of carbohydrate, protein, fibre, minerals, vitamins, essential amino acids and very minute concentration of fat. (
  • 4 Edible mushrooms are low calorie-low fat food supplement with generous amount of proteins, carbohydrates, vitamins, minerals amino acids 5 and dietary fibre. (
  • PDE5 exhibited time- and concentration-dependent reversible activation in response to cGMP, with the highest activation (9- to 11-fold) observed at low substrate concentrations (0.1 micro M cGMP). (
  • The stimulatory effect of cGMP binding on the catalytic activity of PDE5 suggests that this mechanism of enzyme activation may be common among other GAF domain-containing proteins. (
  • Since PKA is known to stimulate SR Ca2+ release by phosphorylating ryanodine receptors, the present findings provide an important link between the activation of GC with NO donors and the NO-dependent mobilization of SR Ca2+ in SA node which we reported previously. (
  • H 2 S regulates various pathophysiological functions via interaction with nitric oxide, activation of molecular signalling cascades, post-translational modification of proteins and control of redox-dependent responses. (
  • Importantly, the Toll-like receptor (TLR) adaptor protein TRIF is required for both inflammasome activation and IFN-β production, indicating its central role in the detection of microbial viability. (
  • Our aim is to identify cCMP-binding and -acitvated proteins and to elucidate whether cCMP plays a role as second messenger. (
  • We confirmed that cCMP activates the purified cyclic nucleotide-dependent protein kinases cAK and cGK. (
  • Then we investigated the effect of cCMP on purified cyclic nucleotide-dependent protein kinases and on intact tissues of wildtype (WT) and cGKI-knockout (KO) mice, namely jejunum, lung and brain. (
  • We identified various protein kinases as cCMP-binding proteins in tissue lysates. (
  • This oxidation directly activated the kinase in vitro, and in rat cells and tissues. (
  • The in vitro cell and kinase assays found that compounds 2 and 29 showed highly potent activity against necroptosis (EC50 = 3.7 and 3.2 nM) and high RIPK1 inhibitory activity (Kd = 9.7 and 70 nM). (
  • [ 40 , 47 ] Two recent studies identified STING and the cytoplasmic helicase DDX41 as host cell receptors for c-di-AMP and c-di-GMP. (
  • Tumor angiogenesis also involves the vascular endothelium-induced stimulation of cancer cell growth (1) and the higher expression levels of certain "cell survival proteins", such as the Inhibitor of Apoptosis Proteins (IAPs, including c-IAP1, Livin and Survivin), which are expressed in both the proliferating cancer cells (2, 3) and the vascular endothelial cells involved in tumor angiogenesis (4). (
  • The activity of the channel is increased by KT-5823, a highly selective inhibitor of protein kinase G (PKG), while it is decreased by direct application of active PKG. (
  • After ligand binding, NPRA is rapidly internalized and trafficked from the cell surface into endosomes, Res and lysosomes, with concurrent generation of intracellular cyclic GMP in HEK-293 cells. (
  • Furthermore, PKG participates in a ligand-dependent gain-of-function loop that significantly increases the intrinsic cyclase activity of the receptor. (
  • Lack of association between polymorphism of the human cyclic GMP-dependent protein kinase gene and obesity. (
  • Defense gene induction in tobacco by nitric oxide, cyclic GMP, and cyclic ADP-ribose. (
  • Western blot analyses showed that anti-angiogenic concentrations of resveratrol suppress endogenous PKG kinase activity and decrease the expression of four cell-survival proteins, c-IAP1, c-IAP2, livin and XIAP. (
  • 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. (
  • 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. (
  • Specifically, resveratrol has been shown to inhibit the kinase (catalytic) activity of several PKC isoforms, the MAP-kinase ERK1/2 and Syk, a tyrosine protein kinase ( 1 ). (
  • Of particular interest are the kinase inhibitory effects of resveratrol. (
  • A family of inhibitory proteins which bind to the REL PROTO-ONCOGENE PROTEINS and modulate their activity. (
  • Application of KT-5823 induces Ca(2+) influx in the endothelial cells isolated from small mesenteric arteries, and it also causes endothelium-dependent relaxations in isolated small mesenteric arteries. (
  • His Kinase and Signal transduction study in the realm of Cell biology interacts with subjects such as Vascular smooth muscle. (
  • these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. (
  • We have found that a combination of: 1) the variable sequence of the C-terminus of the bait with 2) a C-terminal valine "cloning scar" present in a commercially available ORF library, can in some cases create a peptide motif that results in the aberrant co-purification of endogenous cellular proteins. (
  • Specific for endogenous levels of the ~76 kDa SERT protein phosphorylated at Thr276. (
  • Cyclic GMP can directly stimulate If but it is ∼10-fold less potent than the 'physiological' If-gating nucleotide, cAMP. (
  • Most notably, the bacterially-produced cyclic dinucleotides c-di-AMP and c-di-GMP stimulate robust production of type-I IFN, which is also a hallmark response to viable bacteria. (
  • This correlates with the finding that the calcium-dependent protein kinase, PfCDPK1, is phosphorylated by PfPKG, as are components of the actomyosin complex, providing mechanistic insight into the essential role of PfPKG in parasite egress and invasion. (
  • elevated levels of cyclic gmp also reduce calcium entry which also contributing to relaxation. (
  • VEGF, EGF) and apoptosis/cell death-regulating proteins ( e.g. survivin, p53, Bcl-2) ( 1 ). (
  • Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP. (
  • MicroRNAs (miRs) posttranscriptionally regulate mRNA and its translation into protein, and are considered master controllers of genes modulating normal physiology and disease. (
  • The RpfB-Dependent Quorum Sensing Signal Turnover System Is Required for Adaptation and Virulence in Rice Bacterial Blight Pathogen Xanthomonas oryzae pv. (
  • Cyclic dinucleotides are bacterial second messenger molecules, which were recently shown to activate innate immune responses. (
  • The differentiation of mesenchymal cells into chondroblasts is regulated by the activity of the Sox9 transcription factor, which controls the expression of principal genes encoding the extracellular matrix proteins of cartilage, such as collagen type II and aggrecan [ 4 ]. (
  • Radioresistant cells initiate lymphocyte-dependent lung inflammation and IFN? (
  • BAT consists of a group of specialized cells with abundant uncoupling protein 1 (UCP1) in the inner mitochondrial membrane and also fulfills endocrine functions. (
  • Intermediate filament proteins have been isolated from ME-180, cells of a human cervical carcinoma. (
  • The affinity of the kinase for substrates it phosphorylates was enhanced by disulfide formation. (
  • XV" YOL105C 1 15 18 YOL105C "Putative integral membrane protein containing novel cysteine motif. (
  • Additionally, mutations within pseudokinase domains are known to underlie human diseases, suggesting that these proteins may represent new and unexplored therapeutic targets. (
  • Eight of these proteins have been identified as keratins by immunologic cross-reactivity to antibodies raised against authentic human epidermal keratins. (
  • Dawn of the dead: protein pseudokinases signal new adventures in cell biology. (
  • Vinpocetine Inhibits NF-κB-Dependent Inflammation in Acute Ischemic Stroke Patients. (
  • In the CYTOPLASM , I-kappa B proteins bind to the transcription factor NF-KAPPA B. Cell stimulation causes its dissociation and translocation of active NF-kappa B to the nucleus. (