Protein kinase N2 connects blood flow with NO production in a double AKT.
Protein kinase N2 connects blood flow with NO production in a double AKT.
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蛋白激酶 N2 将双 AKT 中的血流与 NO 产生联系起来。
DOI：
10.1172/jci154256
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Stepp,DavidW
中科院分区：
文献类型：
--
作者：
Fulton,DavidJr;Stepp,DavidW
切应力是血流的重要调节因子，并且管腔内皮细胞（EC）感觉到摩擦力的增加并以适当的血管活性介质的释放来响应。在本期的JCI杂志中，Jin等人确定了内皮细胞对剪切力的反应机制，即内皮细胞NOS（eNOS）激活和NO释放。作者表明，PKN 2被流体剪切应力激活，并通过双重作用-通过AKT在丝氨酸1177（S1177）处的间接磷酸化和S1179位点的直接磷酸化促进eNOS激活。两个位点的磷酸化单独增加eNOS活性，但它们一起具有累加效应。总之，这些发现揭示了关于剪切力如何调节eNOS的令人兴奋的细节，并对血流和血压具有重要意义。
Shear stress is an important regulator of blood flow, and luminal endothelial cells (ECs) sense increases in frictional forces and respond with an appropriate release of vasoactive mediators. In this issue of theJCI, Jin et al. identified a mechanism by which ECs respond to shear stress with endothelial NOS (eNOS) activation and NO release. The authors showed that PKN2 was activated by fluid shear stress and contributed to eNOS activation via a double play — indirect phosphorylation at serine 1177 (S1177) via AKT and direct phosphorylation of the S1179 site. Phosphorylation of both sites individually increased eNOS activity, but together they had an additive effect. In sum, these findings reveal exciting details about how shear stress regulates eNOS and have important implications for blood flow and blood pressure.