Role of eNOS phosphorylation at Ser-116 in regulation of eNOS activity in endothelial cells

Chunying Li, Ling Ruan, Sarika G. Sood, Andreas Papapetropoulos, David Fulton, Richard C. Venema

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine to l-citrulline and nitric oxide (NO), an important modulator of vascular function. eNOS is regulated post-translationally through phosphorylation/dephosphorylation at a number of specific phosphorylation sites including Ser-116 in the bovine eNOS sequence. Whether phosphorylation of eNOS at Ser-116 in endothelial cells is stimulatory or inhibitory has not previously been definitively determined. In this study we show that mimicking phosphorylation of eNOS at Ser-116 by Asp mutation reduces basal NO release from endothelial cells. Preventing phosphorylation at this site by Ala mutation increases the amount of NO release from endothelial cells in response to agonist stimulation. In addition, mimicking phosphorylation of Ser-116 increases eNOS association with caveolin-1 and reduces the vascular reactivity of intact aortic rings. eNOS phosphorylation at Ser-116, therefore, appears to contribute to negative modulation of eNOS activity and hence to regulation of vascular tone.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalVascular Pharmacology
Volume47
Issue number5-6
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type III
Endothelial Cells
Phosphorylation
Blood Vessels
Nitric Oxide
Caveolin 1
Citrulline
Mutation
Arginine

Keywords

  • eNOS
  • Nitric oxide
  • Phosphorylation
  • Protein-protein interactions

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Role of eNOS phosphorylation at Ser-116 in regulation of eNOS activity in endothelial cells. / Li, Chunying; Ruan, Ling; Sood, Sarika G.; Papapetropoulos, Andreas; Fulton, David; Venema, Richard C.

In: Vascular Pharmacology, Vol. 47, No. 5-6, 01.11.2007, p. 257-264.

Research output: Contribution to journalArticle

Li, Chunying ; Ruan, Ling ; Sood, Sarika G. ; Papapetropoulos, Andreas ; Fulton, David ; Venema, Richard C. / Role of eNOS phosphorylation at Ser-116 in regulation of eNOS activity in endothelial cells. In: Vascular Pharmacology. 2007 ; Vol. 47, No. 5-6. pp. 257-264.
@article{97866db13b584cf583ba03e73ee89ca6,
title = "Role of eNOS phosphorylation at Ser-116 in regulation of eNOS activity in endothelial cells",
abstract = "Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine to l-citrulline and nitric oxide (NO), an important modulator of vascular function. eNOS is regulated post-translationally through phosphorylation/dephosphorylation at a number of specific phosphorylation sites including Ser-116 in the bovine eNOS sequence. Whether phosphorylation of eNOS at Ser-116 in endothelial cells is stimulatory or inhibitory has not previously been definitively determined. In this study we show that mimicking phosphorylation of eNOS at Ser-116 by Asp mutation reduces basal NO release from endothelial cells. Preventing phosphorylation at this site by Ala mutation increases the amount of NO release from endothelial cells in response to agonist stimulation. In addition, mimicking phosphorylation of Ser-116 increases eNOS association with caveolin-1 and reduces the vascular reactivity of intact aortic rings. eNOS phosphorylation at Ser-116, therefore, appears to contribute to negative modulation of eNOS activity and hence to regulation of vascular tone.",
keywords = "eNOS, Nitric oxide, Phosphorylation, Protein-protein interactions",
author = "Chunying Li and Ling Ruan and Sood, {Sarika G.} and Andreas Papapetropoulos and David Fulton and Venema, {Richard C.}",
year = "2007",
month = "11",
day = "1",
doi = "10.1016/j.vph.2007.07.001",
language = "English (US)",
volume = "47",
pages = "257--264",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier Inc.",
number = "5-6",

}

TY - JOUR

T1 - Role of eNOS phosphorylation at Ser-116 in regulation of eNOS activity in endothelial cells

AU - Li, Chunying

AU - Ruan, Ling

AU - Sood, Sarika G.

AU - Papapetropoulos, Andreas

AU - Fulton, David

AU - Venema, Richard C.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine to l-citrulline and nitric oxide (NO), an important modulator of vascular function. eNOS is regulated post-translationally through phosphorylation/dephosphorylation at a number of specific phosphorylation sites including Ser-116 in the bovine eNOS sequence. Whether phosphorylation of eNOS at Ser-116 in endothelial cells is stimulatory or inhibitory has not previously been definitively determined. In this study we show that mimicking phosphorylation of eNOS at Ser-116 by Asp mutation reduces basal NO release from endothelial cells. Preventing phosphorylation at this site by Ala mutation increases the amount of NO release from endothelial cells in response to agonist stimulation. In addition, mimicking phosphorylation of Ser-116 increases eNOS association with caveolin-1 and reduces the vascular reactivity of intact aortic rings. eNOS phosphorylation at Ser-116, therefore, appears to contribute to negative modulation of eNOS activity and hence to regulation of vascular tone.

AB - Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine to l-citrulline and nitric oxide (NO), an important modulator of vascular function. eNOS is regulated post-translationally through phosphorylation/dephosphorylation at a number of specific phosphorylation sites including Ser-116 in the bovine eNOS sequence. Whether phosphorylation of eNOS at Ser-116 in endothelial cells is stimulatory or inhibitory has not previously been definitively determined. In this study we show that mimicking phosphorylation of eNOS at Ser-116 by Asp mutation reduces basal NO release from endothelial cells. Preventing phosphorylation at this site by Ala mutation increases the amount of NO release from endothelial cells in response to agonist stimulation. In addition, mimicking phosphorylation of Ser-116 increases eNOS association with caveolin-1 and reduces the vascular reactivity of intact aortic rings. eNOS phosphorylation at Ser-116, therefore, appears to contribute to negative modulation of eNOS activity and hence to regulation of vascular tone.

KW - eNOS

KW - Nitric oxide

KW - Phosphorylation

KW - Protein-protein interactions

UR - http://www.scopus.com/inward/record.url?scp=35548954714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35548954714&partnerID=8YFLogxK

U2 - 10.1016/j.vph.2007.07.001

DO - 10.1016/j.vph.2007.07.001

M3 - Article

C2 - 17822962

AN - SCOPUS:35548954714

VL - 47

SP - 257

EP - 264

JO - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

IS - 5-6

ER -