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

David Fulton, Jean-Philippe Gratton, Timothy J. McCabe, Jason Fontana, Yasushi Fujio, Kenneth Walsh, Thomas F. Franke, Andreas Papapetropoulos and William C. Sessa ()
Additional contact information
David Fulton: Boyer Center for Molecular Medicine, Yale University School of Medicine
Jean-Philippe Gratton: Boyer Center for Molecular Medicine, Yale University School of Medicine
Timothy J. McCabe: Boyer Center for Molecular Medicine, Yale University School of Medicine
Jason Fontana: Boyer Center for Molecular Medicine, Yale University School of Medicine
Yasushi Fujio: Cardiovascular Research, St. Elizabeth's Medical Center
Kenneth Walsh: Cardiovascular Research, St. Elizabeth's Medical Center
Thomas F. Franke: Columbia University
Andreas Papapetropoulos: Boyer Center for Molecular Medicine, Yale University School of Medicine
William C. Sessa: Boyer Center for Molecular Medicine, Yale University School of Medicine

Nature, 1999, vol. 399, issue 6736, 597-601

Abstract: Abstract Endothelial nitric oxide synthase (eNOS) is the nitric oxide synthase isoform responsible for maintaining systemic blood pressure, vascular remodelling and angiogenesis1,2,3,4. eNOS is phosphorylated in response to various forms of cellular stimulation5,6,7 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.

Date: 1999
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/21218 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:399:y:1999:i:6736:d:10.1038_21218

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/21218

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().