Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 32PO4-labeled adipocytes, isoproterenol (ISO) or physiologically relevant concentrations of insulin rapidly increased phosphorylation of a particulate 135-kDa protein which has been identified as a cGMP-inhibited "low Km" cAMP phosphodiesterase (CGI-PDE) by several criteria, including selective immunoprecipitation with anti-CGI-PDE IgG (Degerman, E., Smith, C.J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V.C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 533-537). The time courses and concentration dependences for phosphorylation of CGI-PDE by ISO and insulin correlated with CGI-PDE activation in the presence of these agents; effects of ISO were somewhat more rapid than those of insulin. Adenosine deaminase, which metabolizes the adenylate cyclase inhibitor adenosine, also rapidly induced phosphorylation and activation of CGI-PDE. Phenylisopropyladenosine (an adenosine deaminase-resistant adenosine analog) prevented or reversed both adenosine deaminase-stimulated phosphorylation and activation of CGI-PDE (IC50 approximately 0.2 nM). Incubation of adipocytes with 0.1 nM insulin in the presence of ISO rapidly produced 30-200% greater activation and phosphorylation of CGI-PDE than the expected added effects of insulin and ISO individually; both effects preceded the insulin-induced decreases in protein kinase A activity and inhibition of lipolysis. These and other results indicate that CGI-PDE can be phosphorylated at distinct sites and activated by cAMP-dependent and insulin-dependent serine kinase(s), that the activation state of CGI-PDE reflects its relative phosphorylation state, and that synergistic phosphorylation/activation of CGI-PDE may be important in the antilipolytic action of insulin.
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PMID:Hormone-sensitive cyclic GMP-inhibited cyclic AMP phosphodiesterase in rat adipocytes. Regulation of insulin- and cAMP-dependent activation by phosphorylation. 164 89

8-Chloroadenosine 3',5'-monophosphate has been reported to inhibit growth of various mammalian cell lines at micromolar concentrations. We have used Chinese hamster ovary cell lines with mutated cyclic AMP-dependent protein kinase or altered cyclic nucleotide metabolism to show that a metabolite, 8-chloroadenosine, is formed in the medium and is the active inhibitor of cell growth in Chinese hamster ovary cells. Adding adenosine deaminase to the Chinese hamster ovary cell growth media removes the inhibition of cell growth attributed to 8-chloroadenosine 3',5'-monophosphate. Adenosine deaminase or dipyridamole also protects Molt-4 lymphoblasts from the growth-inhibitory effects of 8-chloroadenosine 3',5'-monophosphate.
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PMID:8-Chloroadenosine 3',5'-monophosphate inhibits the growth of Chinese hamster ovary and Molt-4 cells through its adenosine metabolite. 193 80

This report demonstrates that platelets possess P2 purinoceptors with unique properties that distinguish them from the ADP (P2T) receptor. Extracellular ATP, and its poorly hydrolyzable analogues, inhibit collagen- and U46619 (a thromboxane mimetic)-induced platelet aggregations. Adenosine deaminase was without effect on ATP action while reversing the inhibitory effect of adenosine. A unique aspect of the P2 receptor is the sensitivity to UTP and CTP and insensitivity to GTP. The rank order of inhibition by beta gamma-methylene ATP, alpha beta-methylene ATP > ATP indicates that a P2x-like receptor is present on the platelet membrane. This conclusion is further supported by the nearly complete desensitization to ATP by pre-exposure of platelets to alpha beta-methylene-ATP. However, unlike previously described P2x purinoceptors, the inhibition of platelet aggregation by extracellular ATP appears to result, at least in part, from the ATP-induced increase of intracellular cyclic AMP levels apparently coupled through a Gs protein. The combined addition of iloprost (0.14 to 1.39 nM) and ATP (18 microM) or ATP (20-40 microM) and the phosphodiesterase inhibitor theophylline (0.5 to 1 mM) synergistically inhibited platelet aggregation implying a common interactive site with adenylate cyclase. This is further substantiated by the ability of the adenylate cyclase inhibitor, 2',5'-dideoxyadenosine, to abrogate the inhibitory effects of ATP. The protein kinase A (PKA) inhibitor H1004 blocks ATP inhibition of platelet aggregation while the protein kinase C inhibitor H7 did not. This implies that the generation of cyclic AMP, with the subsequent activation of PKA and phosphorylation of selected proteins is required, in part, for the action of ATP.
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PMID:Occupancy of P2 purinoceptors with unique properties modulates the function of human platelets. 768 12

We studied how extracellular cyclic AMP (cAMP) dilates the isolated and perfused canine coronary artery using pharmacological tools. Single injections of cAMP (1-1000 nmol), adenosine 3',5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMPS) (10-1000 nmol, an agonist of the cell surface cAMP receptor in Dictyostelium discoideum and of cAMP-dependent protein kinase), adenosine (0.1-1000 nmol) and 5'-AMP (0.1-1000 nmol) dilated the canine coronary artery dose dependently. The potency order for vasodilation was adenosine > 5'-AMP > cAMP > Sp-cAMPS > 8-bromo-cyclic GMP > 3'-AMP > 8-bromo-cAMP > N6,O2'-dibutyryl-cAMP. 2'-Deoxy-cAMP, 2',3'-cAMP, guanosine, cGMP, 3'-GMP and 5'-GMP did not produce vasodilation. Adenosine antagonists such as aminophylline (1-100 microM, nonselective), 8-phenyltheophylline (0.1-10 microM, A1 selective), 8-cyclopentyl-1,3-dipropylxanthine (0.01-1 microM, A1 selective) and 3,7-dimethyl-1-proparglyxanthine (0.01-1 microM, A2 selective) shifted the dose-response curve of adenosine in parallel to the right, but they shifted that of cAMP to the right and downwards. 8-Phenyltheophylline (1 and 10 microM) inhibited the response to Sp-cAMPS (100 nmol) dose dependently. Aminophylline (10 microM) did not affect isoproterenol- and forskolin-induced vasodilations. Adenosine deaminase (3 U/ml) completely inhibited the response to adenosine, but not those to 5'-AMP, cAMP, 8-bromo-cAMP and Sp-cAMPS. 5'-Nucleotidase inhibitors, adenosine-5'-(alpha,beta-methylene) diphosphate (10 microM) and 5'-GMP (1 mM), inhibited the responses to cAMP and 5'-AMP, but not that to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological analysis of vasodilation induced by extracellular adenosine 3',5'-cyclic monophosphate in the isolated and perfused canine coronary artery. 838 43

Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA binding protein and RNA-editing enzyme that modifies cellular and viral RNAs, including coding and noncoding RNAs. This interferon (IFN)-induced protein was expected to have an antiviral role, but recent studies have demonstrated that it promotes the replication of many RNA viruses. The data from these experiments show that ADAR1 directly enhances replication of hepatitis delta virus, human immunodeficiency virus type 1, vesicular stomatitis virus, and measles virus. The proviral activity of ADAR1 occurs through two mechanisms: RNA editing and inhibition of RNA-activated protein kinase (PKR). While these pathways have been found independently, the two mechanisms can act in concert to increase viral replication and contribute to viral pathogenesis. This novel type of proviral regulation by an IFN-induced protein, combined with some antiviral effects of hyperediting, sheds new light on the importance of ADAR1 during viral infection and transforms our overall understanding of the innate immune response.
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PMID:Enhancement of replication of RNA viruses by ADAR1 via RNA editing and inhibition of RNA-activated protein kinase. 2149 91