Rho-kinase phosphorylates eNOS at threonine 495 in endothelial cells
Rho-kinase phosphorylates eNOS at threonine 495 in endothelial cells
复制标题
DOI：
10.1016/j.bbrc.2007.07.030
复制
发表时间：
2007-09-21
影响因子：
3.1
通讯作者：
Kaibuchi, Kozo
中科院分区：
文献类型：
--
作者：
Sugimoto, Masayuki;Nakayama, Masanori;Kaibuchi, Kozo
内皮型一氧化氮合酶（eNOS）产生一氧化氮（NO），参与心血管系统的多种生理功能。eNOS通过Thr 495的去磷酸化和Ser 1177的磷酸化而被激活。Rho激酶是小GTdR RhoA的效应子，抑制Rho激酶导致Akt/PKB的激活，Akt/PKB使eNOS在Ser 1177处磷酸化，从而促进NO产生。然而，关于Rho激酶对Thr 495磷酸化的影响知之甚少。我们在这里发现，组成型活性形式的Rho激酶在体外磷酸化eNOS在Thr 495。组成型活性形式的RhoA或Rhokinase的表达增加了COS-7细胞中的这种磷酸化。添加凝血酶培养的人脐静脉内皮细胞诱导eNOS在Thr 495磷酸化。用Y27632（Rho激酶抑制剂）处理抑制凝血酶诱导的Thr 495磷酸化。这些结果表明，Rho激酶可以直接磷酸化eNOS的Thr 495抑制NO的产生在内皮细胞。(c)2007年爱思唯尔公司All rights reserved.
Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO), which is involved in various physiological functions of the cardiovascular system. eNOS is activated by dephosphorylation at Thr495 and phosphorylation at Ser1177. Inhibition of Rho-kinase, an effector of the small GTPase RhoA, leads to activation of Akt/PKB, which phosphorylates eNOS at Ser1177 and thereby promotes NO production. However, little is known about the effects of Rho-kinase on phosphorylation of Thr495. We here found that the constitutively active form of Rho-kinase phosphorylated eNOS at Thr495 in vitro. Expression of the constitutively active form of RhoA or Rhokinase increased this phosphorylation in COS-7 cells. Addition of thrombin to cultured human umbilical vein endothelial cells induced phosphorylation of eNOS at Thr495. Treatment with Y27632, a Rho-kinase inhibitor, suppressed thrombin-induced phosphorylation at Thr495. These results indicate that Rho-kinase can directly phosphorylate eNOS at Thr495 to suppress NO production in endothelium. (c) 2007 Elsevier Inc. All rights reserved.