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

David J 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 journalArticle

1971 Citations (Scopus)

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

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Nitric Oxide Synthase Type III
Protein Kinases
Nitric Oxide
Phosphorylation
Proto-Oncogene Proteins c-akt
Protein-Serine-Threonine Kinases
Second Messenger Systems
Adenoviridae
Nitric Oxide Synthase
Serine
Vascular Endothelial Growth Factor A
Signal Transduction
Protein Isoforms
Phosphotransferases
Endothelial Cells
Blood Pressure
Enzymes
Genes

ASJC Scopus subject areas

  • General

Cite this

Fulton, D. J., Gratton, J. P., McCabe, T. J., Fontana, J., Fujio, Y., Walsh, K., ... Sessa, W. C. (1999). Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature, 399(6736), 597-601. https://doi.org/10.1038/21218

Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. / Fulton, David J; Gratton, Jean Philippe; McCabe, Timothy J.; Fontana, Jason; Fujio, Yasushl; Walsh, Kenneth; Franke, Thomas F.; Papapetropoulos, Andreas; Sessa, William C.

In: Nature, Vol. 399, No. 6736, 10.06.1999, p. 597-601.

Research output: Contribution to journalArticle

Fulton, DJ, Gratton, JP, McCabe, TJ, Fontana, J, Fujio, Y, Walsh, K, Franke, TF, Papapetropoulos, A & Sessa, WC 1999, 'Regulation of endothelium-derived nitric oxide production by the protein kinase Akt', Nature, vol. 399, no. 6736, pp. 597-601. https://doi.org/10.1038/21218
Fulton DJ, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999 Jun 10;399(6736):597-601. https://doi.org/10.1038/21218
Fulton, David J ; Gratton, Jean Philippe ; McCabe, Timothy J. ; Fontana, Jason ; Fujio, Yasushl ; Walsh, Kenneth ; Franke, Thomas F. ; Papapetropoulos, Andreas ; Sessa, William C. / Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. In: Nature. 1999 ; Vol. 399, No. 6736. pp. 597-601.
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