Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 조인호 | * |
dc.contributor.author | 서정원 | * |
dc.date.accessioned | 2016-08-28T12:08:45Z | - |
dc.date.available | 2016-08-28T12:08:45Z | - |
dc.date.issued | 2010 | * |
dc.identifier.issn | 0194-911X | * |
dc.identifier.other | OAK-6227 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/220491 | - |
dc.description.abstract | Nitric oxide (NO) production in endothelial cells (EC) is regulated by multisite phosphorylation of specific serine and threonine residues in endothelial NO synthase (eNOS). Among these, eNOS-Ser116 is phosphorylated in the basal state, and its phosphorylation contributes to basal NO production. Here, we investigated the mechanism by which eNOS-Ser116 is phosphorylated during the basal state using bovine aortic EC. Although a previous study suggested that protein kinase C was involved in eNOS-Ser116 phosphorylation, overexpression of various protein kinase C isoforms did not affect eNOS-Ser116 phosphorylation. An in silico analysis using a motif scan revealed that the eNOS-Ser116 residue might be a substrate for proline-directed protein kinases. Roscovitine, a specific inhibitor of cyclin-dependent kinase (CDK), 1, 2, and 5, but not an inhibitor of mitogen-activated protein kinase kinase or glycogen synthase kinase 3β, inhibited eNOS-Ser116 phosphorylation dose dependently. Furthermore, purified CDK1, 2, or 5 directly phosphorylated eNOS-Ser116 in vitro. Ectopic expression of the dominant-negative CDK5 but not dominant-negative CDK1 or dominant-negative CDK2 repressed eNOS-Ser116 phosphorylation and increased NO production. In addition, CDK5 activity was detected in bovine aortic EC, and coimmunoprecipitation and confocal microscopy studies revealed a colocalization of eNOS and CDK5. Cotransfection of CDK5 and p25, the specific CDK5 activator, increased eNOS-Ser116 phosphorylation and decreased NO production, but its parent molecule, p35, and p39, another activator, were not detected in bovine aortic EC, which suggests the existence of a novel CDK5 activator. Overall, this is the first study to find that CDK5 is a physiological kinase responsible for eNOS-Ser116 phosphorylation and regulation of NO production. © 2010 American Heart Association. All rights reserved. | * |
dc.language | English | * |
dc.title | Cyclin-dependent kinase 5 phosphorylates endothelial nitric oxide synthase at serine 116 | * |
dc.type | Article | * |
dc.relation.issue | 2 | * |
dc.relation.volume | 55 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 345 | * |
dc.relation.lastpage | 352 | * |
dc.relation.journaltitle | Hypertension | * |
dc.identifier.doi | 10.1161/HYPERTENSIONAHA.109.140210 | * |
dc.identifier.wosid | WOS:000273802500028 | * |
dc.identifier.scopusid | 2-s2.0-74949143633 | * |
dc.author.google | Cho D.-H. | * |
dc.author.google | Seo J. | * |
dc.author.google | Park J.-H. | * |
dc.author.google | Jo C. | * |
dc.author.google | Choi Y.J. | * |
dc.author.google | Soh J.-W. | * |
dc.author.google | Jo I. | * |
dc.contributor.scopusid | 조인호(26643129000;56663841900) | * |
dc.date.modifydate | 20240123112949 | * |