PKC is required for activation of ROCK by RhoA in human endothelial cells

被引:39
作者
Barandier, C
Ming, XF
Rusconi, S
Yang, ZH
机构
[1] Univ Fribourg, Dept Med, Div Physiol, CH-1700 Fribourg, Switzerland
[2] Univ Fribourg, Div Biochem, CH-1700 Fribourg, Switzerland
基金
新加坡国家研究基金会;
关键词
endothelial cells; eNOS; RhoA; ROCK; signal transduction; PKC; thrombin;
D O I
10.1016/S0006-291X(03)00668-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Rho/Rho-kinase (ROCK) complex formation is the only proposed mechanism for ROCK activation. Rho/ROCK and PKC can exhibit a convergence of cellular effects such as suppression of endothelial nitric oxide synthase (eNOS) expression. We, therefore, investigated the role of PKC in RhoA/ROCK complex formation and activation linked to eNOS expression in cultured human umbilical vein endothelial cells. We showed that expression of constitutively active RhoA (Rho63) or ROCK (CAT) suppressed eNOS gene expression. This effect of Rho63 but not that of CAT was abolished by phorbol ester-sensitive PKC depletion. Accordingly, depletion or inhibition of PKC prevented ROCK activation by Rho63 without affecting RhoA/ROCK complex formation. Similarly, suppression of eNOS expression and activation of ROCK, but not RhoA by thrombin were prevented by PKC inhibition or depletion. These results indicate that RhoA/ROCK complex formation alone is not sufficient and PKC is required for RhoA-induced ROCK activation leading to eNOS gene suppression. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:714 / 719
页数:6
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