ROCK1 feedback regulation of the upstream small GTPase RhoA.
ROCK1 feedback regulation of the upstream small GTPase RhoA.
复制标题
DOI：
10.1016/j.cellsig.2012.03.005
复制
发表时间：
2012-07
影响因子：
4.8
通讯作者：
Nithipatikom K
中科院分区：
文献类型：
--
作者：
Tang AT;Campbell WB;Nithipatikom K
Rho相关卷曲螺旋蛋白激酶1（ROCK1）是小GTdR RhoA的关键下游效应子。靶向ROCK1已在癌症、心脏保护、高血压、糖尿病、神经元再生和干细胞生物学中显示出有前景的临床潜力。以往研究中的一般工作假设集中于ROCK 1作为RhoA信号通路中的下游序列的功能。在这项研究中，直接抑制ROCK 1对上游RhoA和Rac 1的活性的影响进行了研究，使用相结合的药理学和遗传学的方法。我们报告了一个有趣的机制，通过该机制，ROCK 1的抑制间接减少了通过Tiam 1诱导的Rac 1活性的刺激上游RhoA的活性。ROCK 1介导上游Rac 1和RhoA活性的这种新型反馈机制，为ROCK 1对Rho小GTPases家族功能平衡的不同影响提供了相当多的见解，该家族调节肌动蛋白细胞骨架重组过程和由此产生的整体细胞行为。
Rho-associated coiled-coil containing protein kinase 1 (ROCK1) is a key downstream effector of the small GTPase RhoA. Targeting ROCK1 has shown promising clinical potential in cancer, cardioprotection, hypertension, diabetes, neuronal regeneration, and stem cell biology. General working hypothesis in previous studies has centered on the function of ROCK1 as a downstream sequence in the RhoA signaling pathway. In this study, the effects of the direct inhibition of ROCK1 on the activity of upstream RhoA and Rac1 were examined using a combined pharmacological and genetic approach. We report an intriguing mechanism by which the inhibition of ROCK1 indirectly diminishes the activity of upstream RhoA through the stimulation of Tiam1-induced Rac1 activity. This novel feedback mechanism, in which ROCK1 mediates upstream Rac1 and RhoA activity, offers considerable insight into the diverse effects of ROCK1 on the functional balance of the Rho family of small GTPases, which regulates actin cytoskeleton reorganization processes and the resulting overall behavior of cells.
登录
查看更多内容
影响因子：
2.9
作者：
Greenberg, DL;Mize, GJ;Takayama, TK
通讯作者：
Takayama, TK
影响因子：
4.8
作者：
Hoshinoso, M;Sone, M;Hama, C
通讯作者：
Hama, C
影响因子：
4.8
作者：
Kelly, Patrick;Stemmle, Laura N.;Casey, Patrick J.
通讯作者：
Casey, Patrick J.
影响因子：
64.5
作者：
HABETS, GGM;SCHOLTES, EHM;COLLARD, JG
通讯作者：
COLLARD, JG
影响因子：
4.4
作者：
Chiu, CY;Leng, S;Duhl, DMJ
通讯作者：
Duhl, DMJ