Regulation of endothelium-derived nitric oxide production by the protein kinase Akt

David Fulton, Jean Philippe Gratton, Timothy J. McCabe, Jason Fontana, Yasushl Fujio, Kenneth Walsh, Thomas F. Franke, Andreas Papapetropoulos, William C. Sessa

Research output: Contribution to journalArticlepeer-review

2272 Scopus citations

Abstract

Endothelial nitric oxide synthase (eNOS) is the nitric oxide synthase isoform responsible for maintaining systemic blood pressure, vascular remodelling and angiogenesis. eNOS is phosphorylated in response to various forms of cellular stimulation, but the role of phosphorylation in the regulation of nitric oxide (NO) production and the kinase(s) responsible are not known. Here we show that the serine/threonine protein kinase Akt (protein kinase B) can directly phosphorylate eNOS on serine 1179 and activate the enzyme, leading to NO production, whereas mutant eNOS (S1179A) is resistant to phosphorylation and activation by Akt. Moreover, using adenovirus-mediated gene transfer, activated Akt increases basal NO release from endothelial cells, and activation-deficient Akt attenuates NO production stimulated by vascular endothelial growth factor. Thus, eNOS is a newly described Akt substrate linking signal transduction by Akt to the release of the gaseous second messenger NO.

Original languageEnglish (US)
Pages (from-to)597-601
Number of pages5
JournalNature
Volume399
Issue number6736
DOIs
StatePublished - Jun 10 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Regulation of endothelium-derived nitric oxide production by the protein kinase Akt'. Together they form a unique fingerprint.

Cite this