Li Chunying, Ruan Ling, Sood Sarika G, Papapetropoulos Andreas, Fulton David, Venema Richard C
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
Vascul Pharmacol. 2007 Nov-Dec;47(5-6):257-64. doi: 10.1016/j.vph.2007.07.001. Epub 2007 Aug 9.
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.
内皮型一氧化氮合酶（eNOS）催化L-精氨酸转化为L-瓜氨酸和一氧化氮（NO），NO是血管功能的重要调节因子。eNOS通过在包括牛eNOS序列中Ser-116在内的多个特定磷酸化位点进行磷酸化/去磷酸化而受到翻译后调控。内皮细胞中eNOS在Ser-116处的磷酸化是具有刺激作用还是抑制作用，此前尚未明确确定。在本研究中，我们表明通过天冬氨酸突变模拟eNOS在Ser-116处的磷酸化会减少内皮细胞的基础NO释放。通过丙氨酸突变阻止该位点的磷酸化会增加内皮细胞在激动剂刺激下的NO释放量。此外，模拟Ser-116的磷酸化会增加eNOS与小窝蛋白-1的结合，并降低完整主动脉环的血管反应性。因此，eNOS在Ser-116处的磷酸化似乎有助于对eNOS活性进行负调节，从而调节血管张力。
