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rdf:type |
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lifeskim:mentions |
umls-concept:C0003009,
umls-concept:C0028778,
umls-concept:C0033681,
umls-concept:C0162764,
umls-concept:C0243077,
umls-concept:C0751984,
umls-concept:C1257792,
umls-concept:C1314939,
umls-concept:C1335273,
umls-concept:C1415615,
umls-concept:C1426113,
umls-concept:C1879547
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pubmed:issue |
19
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pubmed:dateCreated |
2001-5-7
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pubmed:abstractText |
We recently reported the calcium-dependent activation of tyrosine kinase Pyk2 by angiotensin II (Ang II) in pulmonary vein endothelial cells (PVEC). Since Pyk2 has no calcium binding domain, and neither Ca(2+) nor Ca(2+)/calmodulin directly activates Pyk2, it is not clear how Ca(2+) transduces the signal to activate Pyk2, a key tyrosine kinase, in the early events of Ang II signaling. In the present study, we investigated the mechanism of the calcium-dependent activation of Pyk2 in response to Ang II by using 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors and isoprenoid intermediates in PVEC. We have obtained substantial evidence indicating that Ang II activates Pyk2 through calcium-mediated activation of the geranylgeranylated small G protein Rap1 and the Rap1 association with Pyk2. Thus, the small G protein Rap1 is an intermediary signaling molecule linking Ang II-induced calcium signal to Pyk2 activation in PVEC. In addition, our results indicate that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, a class of cholesterol-lowering drugs, could interrupt Ang II signaling independent of cholesterol lowering in endothelial cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2b protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Angiotensin,
http://linkedlifedata.com/resource/pubmed/chemical/Simvastatin,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15761-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11278472-Angiotensin II,
pubmed-meshheading:11278472-Animals,
pubmed-meshheading:11278472-Calcimycin,
pubmed-meshheading:11278472-Calcium,
pubmed-meshheading:11278472-Calmodulin,
pubmed-meshheading:11278472-Cell Membrane,
pubmed-meshheading:11278472-Cells, Cultured,
pubmed-meshheading:11278472-Endothelium, Vascular,
pubmed-meshheading:11278472-Enzyme Activation,
pubmed-meshheading:11278472-Focal Adhesion Kinase 2,
pubmed-meshheading:11278472-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:11278472-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:11278472-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:11278472-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11278472-Protein Prenylation,
pubmed-meshheading:11278472-Protein-Tyrosine Kinases,
pubmed-meshheading:11278472-Pulmonary Veins,
pubmed-meshheading:11278472-Rats,
pubmed-meshheading:11278472-Receptor, Angiotensin, Type 1,
pubmed-meshheading:11278472-Receptor, Angiotensin, Type 2,
pubmed-meshheading:11278472-Receptors, Angiotensin,
pubmed-meshheading:11278472-Simvastatin,
pubmed-meshheading:11278472-Tetradecanoylphorbol Acetate,
pubmed-meshheading:11278472-rap1 GTP-Binding Proteins
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pubmed:year |
2001
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pubmed:articleTitle |
3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors block calcium-dependent tyrosine kinase Pyk2 activation by angiotensin II in vascular endothelial cells. involvement of geranylgeranylation of small G protein Rap1.
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pubmed:affiliation |
Departments of Biochemistry and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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