PMID- 10376602
OWN - NLM
STAT- MEDLINE
DCOM- 19990630
LR  - 20181113
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 399
IP  - 6736
DP  - 1999 Jun 10
TI  - Regulation of endothelium-derived nitric oxide production by the protein kinase
      Akt.
PG  - 597-601
AB  - 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.
FAU - Fulton, D
AU  - Fulton D
AD  - Department of Pharmacology, Boyer Center for Molecular Medicine, Yale University 
      School of Medicine, New Haven, Connecticut 06536, USA.
FAU - Gratton, J P
AU  - Gratton JP
FAU - McCabe, T J
AU  - McCabe TJ
FAU - Fontana, J
AU  - Fontana J
FAU - Fujio, Y
AU  - Fujio Y
FAU - Walsh, K
AU  - Walsh K
FAU - Franke, T F
AU  - Franke TF
FAU - Papapetropoulos, A
AU  - Papapetropoulos A
FAU - Sessa, W C
AU  - Sessa WC
LA  - eng
GR  - R01 AG015052/AG/NIA NIH HHS/United States
GR  - R01 AR040197/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Retroviridae Proteins, Oncogenic)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 452VLY9402 (Serine)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
SB  - IM
EIN - Nature 1999 Aug 19;400(6746):792
MH  - Animals
MH  - COS Cells
MH  - Cattle
MH  - Endothelium, Vascular/*metabolism
MH  - Humans
MH  - Mutation
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/genetics/*metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Oncogene Protein v-akt
MH  - Phosphorylation
MH  - Rats
MH  - Retroviridae Proteins, Oncogenic/*metabolism
MH  - Serine/metabolism
MH  - Signal Transduction
MH  - Transfection
PMC - PMC3637917
MID - NIHMS456150
EDAT- 1999/06/22 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/06/22 10:00
PHST- 1999/06/22 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/06/22 10:00 [entrez]
AID - 10.1038/21218 [doi]
PST - ppublish
SO  - Nature. 1999 Jun 10;399(6736):597-601. doi: 10.1038/21218.