Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress
Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress
复制标题
DOI：
10.1172/jci5367
复制
发表时间：
1999-04-01
影响因子：
15.9
通讯作者：
Chien, S
中科院分区：
文献类型：
--
作者：
Li, S;Chen, BPC;Chien, S
剪应力是血流动力学力的切向分量，在内皮重塑中起重要作用。在本研究中，我们探讨了Rho家族的GTP酶Cdc42和Rho在剪应力诱导的信号转导和细胞骨架重组中的作用。我们的结果表明，剪应力诱导Cdc42和Rho从胞质溶胶转位到细胞膜。尽管Cdc42和Rho都参与剪应力诱导的作用于12 - O - 十四酰基 - 13 - 乙酸佛波酯反应元件（TRE）的转录因子AP - 1，但只有Cdc42足以激活AP - 1/TRE。Cdc42和Rho的显性负性突变体以及重组C3外酶减弱了c - Jun氨基末端激酶（JNKs）的剪应力激活，这表明Cdc42和Rho通过JNKs调节剪应力对AP - 1/TRE活性的诱导。剪应力诱导的细胞排列和应力纤维形成被Rho和p160ROCK的显性负性突变体抑制，但不被Cdc42的显性负性突变体抑制，这表明Rho - p160ROCK通路调节细胞对剪应力的细胞骨架重组反应。
Shear stress, the tangential component of hemodynamic forces, plays an important role in endothelial remodeling. In this study, we investigated the role of Rho family GTPases Cdc42 and Rho in shear stress-induced signal transduction and cytoskeleton reorganization. Our results showed that shear stress induced the translocation of Cdc42 and Rho from cytosol to membrane. Although both Cdc42 and Rho were involved in the shear stress-induced transcription factor AP-1 acting on the 12-O-tetradecanoyl- 13-phorbol-acetate-responsive element (TRE), only Cdc42 was sufficient to activate AP-1/TRE. Dominant-negative mutants of Cdc42 and Rho, as well as recombinant C3 exoenzyme, attenuated the shear stress activation of c-Jun NH2-terminal kinases (JNKs), suggesting that Cdc42 and Rho regulate the shear stress induction of AP-1/TRE activity through JNKs. Shear stress-induced cell alignment and stress fiber formation were inhibited by the dominant-negative mutants of Rho and p160ROCK, but not by the dominant-negative mutant of Cdc42, indicating that the Rho-p160ROCK pathway regulates the cytoskeletal reorganization in response to shear stress.