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.
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Ruan
authors.forename: Sarika G
authors.initials: SG
authors.lastname: Sood
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: David
authors.initials: D
authors.lastname: Fulton
authors.forename: Richard C
authors.initials: RC
authors.lastname: Venema
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*; D014664:Vasodilation