Kim Oekyung, Yang Jianbo, Qiu Yun
Department of Laboratory Medicine and Pathology and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Biol Chem. 2002 Aug 16;277(33):30066-71. doi: 10.1074/jbc.M201713200. Epub 2002 May 22.
Etk/Bmx is a member of the Btk family tyrosine kinase, which contains an N-terminal pleckstrin homology domain. Etk has been shown to play a pivotal role in the regulation of various cellular processes including differentiation, apoptosis, and cell motility. Here we present evidence that Etk is a modulator of the small GTPase RhoA. Etk and RhoA both are translocated to the plasma membrane and can form a complex upon serum stimulation in C2C12 cells. Etk interacts with RhoA but not other closely related small GTPases such as Cdc42 and Rac1, suggesting a specific modulation of RhoA by Etk. Our results demonstrate that Etk activates RhoA and enhances Rho-mediated stress fiber formation and transcription activity in a pleckstrin homology domain-dependent manner. Furthermore, Etk disrupts the interaction between RhoA and Rho-GDI (guanine nucleotide dissociation inhibitor) and promotes the membrane translocation of RhoA. Our data suggest that Etk plays an important role in regulation of RhoA-mediated signaling.
Etk/Bmx是Btk家族酪氨酸激酶的成员，其含有一个N端普列克底物蛋白同源结构域。Etk已被证明在包括分化、凋亡和细胞运动等多种细胞过程的调节中起关键作用。在此我们提供证据表明Etk是小GTP酶RhoA的调节剂。Etk和RhoA在血清刺激下均转位至质膜，且在C2C12细胞中可形成复合物。Etk与RhoA相互作用，但不与其他密切相关的小GTP酶如Cdc42和Rac1相互作用，提示Etk对RhoA有特异性调节作用。我们的结果表明，Etk以普列克底物蛋白同源结构域依赖性方式激活RhoA并增强Rho介导的应力纤维形成和转录活性。此外，Etk破坏RhoA与Rho-GDI（鸟嘌呤核苷酸解离抑制剂）之间的相互作用并促进RhoA的膜转位。我们的数据表明Etk在RhoA介导的信号传导调节中起重要作用。
