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rdf:type |
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lifeskim:mentions |
umls-concept:C0006100,
umls-concept:C0014257,
umls-concept:C0031715,
umls-concept:C0132555,
umls-concept:C0851285,
umls-concept:C0871261,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1882911,
umls-concept:C1948023,
umls-concept:C2911692
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pubmed:issue |
19
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pubmed:dateCreated |
2001-5-7
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pubmed:abstractText |
Endothelial nitric-oxide synthase (eNOS) is phosphorylated at Ser-1179 (bovine sequence) by Akt after growth factor or shear stress stimulation of endothelial cells, resulting in increased eNOS activity. Purified eNOS is also phosphorylated at Thr-497 by purified AMP-activated protein kinase, resulting in decreased eNOS activity. We investigated whether bradykinin (BK) stimulation of bovine aortic endothelial cells (BAECs) regulates eNOS through Akt activation and Ser-1179 or Thr-497 phosphorylation. Akt is transiently activated in BK-stimulated BAECs. Activation is blocked completely by wortmannin and LY294002, inhibitors of phosphatidylinositol 3-kinase, suggesting that Akt activation occurs downstream from phosphatidylinositol 3-kinase. BK stimulates a transient phosphorylation of eNOS at Ser-1179 that is correlated temporally with a transient dephosphorylation of eNOS at Thr-497. Phosphorylation at Ser-1179, but not dephosphorylation at Thr-497, is blocked by wortmannin and LY294002. BK also stimulates a transient nitric oxide (NO) release from BAECs with a time-course similar to Ser-1179 phosphorylation and Thr-497 dephosphorylation. NO release is not altered by wortmannin. BK-stimulated dephosphorylation of Thr-497 and NO release are blocked by the calcineurin inhibitor, cyclosporin A. These data suggest that BK activation of eNOS in BAECs primarily involves deinhibition of the enzyme through calcineurin-mediated dephosphorylation at Thr-497.
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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/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphothreonine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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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 |
16587-91
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11340086-Androstadienes,
pubmed-meshheading:11340086-Animals,
pubmed-meshheading:11340086-Aorta,
pubmed-meshheading:11340086-Bradykinin,
pubmed-meshheading:11340086-Calcineurin,
pubmed-meshheading:11340086-Cattle,
pubmed-meshheading:11340086-Chromones,
pubmed-meshheading:11340086-Cyclosporine,
pubmed-meshheading:11340086-Endothelium, Vascular,
pubmed-meshheading:11340086-Enzyme Activation,
pubmed-meshheading:11340086-Enzyme Inhibitors,
pubmed-meshheading:11340086-Kinetics,
pubmed-meshheading:11340086-Morpholines,
pubmed-meshheading:11340086-Nitric Oxide Synthase,
pubmed-meshheading:11340086-Nitric Oxide Synthase Type III,
pubmed-meshheading:11340086-Phosphorylation,
pubmed-meshheading:11340086-Phosphoserine,
pubmed-meshheading:11340086-Phosphothreonine,
pubmed-meshheading:11340086-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11340086-Protein-Tyrosine Kinases,
pubmed-meshheading:11340086-Proto-Oncogene Proteins,
pubmed-meshheading:11340086-Proto-Oncogene Proteins c-akt
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pubmed:year |
2001
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pubmed:articleTitle |
Reciprocal phosphorylation and regulation of endothelial nitric-oxide synthase in response to bradykinin stimulation.
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pubmed:affiliation |
Vascular Biology Center, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30912, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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