View : 814 Download: 0
Cyclin-dependent kinase 5 phosphorylates endothelial nitric oxide synthase at serine 116
- Title
- Cyclin-dependent kinase 5 phosphorylates endothelial nitric oxide synthase at serine 116
- Authors
- Cho D.-H.; Seo J.; Park J.-H.; Jo C.; Choi Y.J.; Soh J.-W.; Jo I.
- Ewha Authors
- 조인호; 서정원
- SCOPUS Author ID
- 조인호
- Issue Date
- 2010
- Journal Title
- Hypertension
- ISSN
- 0194-911X
- Citation
- Hypertension vol. 55, no. 2, pp. 345 - 352
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1161/HYPERTENSIONAHA.109.140210
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- Export
- RIS (EndNote)
- XLS (Excel)
- XML