• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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

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.

Pubmed ID: 10376602


  • Fulton D
  • Gratton JP
  • McCabe TJ
  • Fontana J
  • Fujio Y
  • Walsh K
  • Franke TF
  • Papapetropoulos A
  • Sessa WC



Publication Data

June 10, 1999

Associated Grants

  • Agency: NIA NIH HHS, Id: R01 AG015052
  • Agency: NIAMS NIH HHS, Id: R01 AR040197

Mesh Terms

  • Animals
  • COS Cells
  • Cattle
  • Endothelium, Vascular
  • Humans
  • Mutation
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Oncogene Protein v-akt
  • Phosphorylation
  • Rats
  • Retroviridae Proteins, Oncogenic
  • Serine
  • Signal Transduction
  • Transfection