Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
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DOI：
10.1038/21218
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发表时间：
1999-06-10
期刊：
影响因子：
64.8
通讯作者：
Sessa, WC
中科院分区：
文献类型：
--
作者：
Fulton, D;Gratton, JP;Sessa, WC
内皮型一氧化氮合酶（eNOS）是负责维持全身血压、血管重塑和血管生成的一氧化氮合酶同种型（1-4），eNOS响应于各种形式的细胞刺激而被磷酸化（5-7），但磷酸化在一氧化氮（NO）产生的调节中的作用和负责的激酶尚不清楚。在这里，我们表明，丝氨酸/苏氨酸蛋白激酶Akt（蛋白激酶B）可以直接磷酸化eNOS的丝氨酸1179和激活酶，导致NO的生产，而突变型eNOS（S1179 A）是耐磷酸化和激活Akt。此外，使用腺病毒介导的基因转移，激活的Akt增加内皮细胞的基础NO释放，而激活缺陷的Akt减弱血管内皮生长因子刺激的NO产生。因此，eNOS是一种新描述的Akt底物，其将Akt的信号转导与气态第二信使NO的释放联系起来。
Endothelial nitric oxide synthase (eNOS) is the nitric oxide synthase isoform responsible for maintaining systemic blood pressure, vascular remodelling and angiogenesis(1-4), eNOS is phosphorylated in response to various forms of cellular stimulation(5-7), 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.