pubmed-article:11278298 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:11278298 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
pubmed-article:11278298 | lifeskim:mentions | umls-concept:C0010536 | lld:lifeskim |
pubmed-article:11278298 | lifeskim:mentions | umls-concept:C0250416 | lld:lifeskim |
pubmed-article:11278298 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
pubmed-article:11278298 | pubmed:issue | 23 | lld:pubmed |
pubmed-article:11278298 | pubmed:dateCreated | 2001-6-4 | lld:pubmed |
pubmed-article:11278298 | pubmed:abstractText | Among the drugs that are known to relax the vascular smooth muscle and regulate other cellular functions, beta-adrenergic agonists and nitric oxide-containing compounds are some of the most effective ones. The mechanisms of these drugs are thought to lower agonist-induced intracellular [Ca(2+)] by increasing intracellular cAMP and cGMP, activating their respective protein kinases. However, the physiological targets of cyclic nucleotide-dependent protein kinases are not clear. The molecular basis for the regulation of intracellular Ca(2+) by signaling pathways coupled to cyclic nucleotides is not well defined. G-protein-activated phospholipase C (PLC-beta) catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphates to generate diacylglycerol and inositol 1,4,5-triphosphate, leading to the activation of protein kinase C and the mobilization of intracellular Ca(2+). In this study, we shown that G-protein-activated PLC enzymes are the potential targets of cGMP-dependent protein kinases (PKG). PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG. Furthermore, mutation of these serine residues removed the inhibitory effect of PKG on the activation of the mutant PLC-beta3 proteins by G-protein subunits. Our results suggest a molecular mechanism for the regulation of G-protein-mediated intracellular [Ca(2+)] by the NO-cGMP-dependent signaling pathway. | lld:pubmed |
pubmed-article:11278298 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11278298 | pubmed:language | eng | lld:pubmed |
pubmed-article:11278298 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11278298 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:11278298 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11278298 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11278298 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:11278298 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11278298 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:11278298 | pubmed:month | Jun | lld:pubmed |
pubmed-article:11278298 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:11278298 | pubmed:author | pubmed-author:LinDD | lld:pubmed |
pubmed-article:11278298 | pubmed:author | pubmed-author:SanbornB MBM | lld:pubmed |
pubmed-article:11278298 | pubmed:author | pubmed-author:BayPP | lld:pubmed |
pubmed-article:11278298 | pubmed:author | pubmed-author:WuZ ZZZ | lld:pubmed |
pubmed-article:11278298 | pubmed:author | pubmed-author:XiaCC | lld:pubmed |
pubmed-article:11278298 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:11278298 | pubmed:day | 8 | lld:pubmed |
pubmed-article:11278298 | pubmed:volume | 276 | lld:pubmed |
pubmed-article:11278298 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:11278298 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:11278298 | pubmed:pagination | 19770-7 | lld:pubmed |
pubmed-article:11278298 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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pubmed-article:11278298 | pubmed:meshHeading | pubmed-meshheading:11278298... | lld:pubmed |
pubmed-article:11278298 | pubmed:year | 2001 | lld:pubmed |
pubmed-article:11278298 | pubmed:articleTitle | Phosphorylation and regulation of G-protein-activated phospholipase C-beta 3 by cGMP-dependent protein kinases. | lld:pubmed |
pubmed-article:11278298 | pubmed:affiliation | Department of Medical Biochemistry and Genetics, Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A & M University System Health Science Center, Houston, Texas 77030, USA. | lld:pubmed |
pubmed-article:11278298 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:11278298 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
pubmed-article:11278298 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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