Takahashi K, Sasaki T, Mammoto A, Hotta I, Takaishi K, Imamura H, Nakano K, Kodama A, Takai Y
Department of Molecular Biology and Biochemistry, Osaka University Medical School, Suita, Japan.
Oncogene. 1998 Jun 25;16(25):3279-84. doi: 10.1038/sj.onc.1201874.
The Rho small G protein family, consisting of the Rho, Rac, and Cdc42 subfamilies, regulates various actin cytoskeleton-dependent cell functions. The Rho subfamily members regulate ERM (ezrin, radixin and moesin)-dependent association of the actin cytoskeleton with the plasma membrane. Moreover, the N-terminal regions of ERM interact with Rho GDI, an inhibitory regulator of all the Rho family members, and reduce its inhibitory action, finally initiating the activation of the Rho family members. We show here that the N-terminal region of radixin furthermore interacts with Dbl, a stimulatory GDP/GTP exchange protein of the Rho family members. This interaction does not affect the Dbl activity to stimulate the GDP/GTP exchange reaction of RhoA, a member of the Rho subfamily. Dbl does not interact with radixin which is precomplexed with Rho GDI, and Rho GDI displaces Dbl from radixin. Thus, radixin plays an important role in activation of the Rho family members by recruiting their positive and negative regulators.
Rho小G蛋白家族由Rho、Rac和Cdc42亚家族组成，调控各种依赖肌动蛋白细胞骨架的细胞功能。Rho亚家族成员调控肌动蛋白细胞骨架与质膜的依赖ERM（埃兹蛋白、根蛋白和膜突蛋白）的结合。此外，ERM的N端区域与Rho GDI相互作用，Rho GDI是所有Rho家族成员的抑制性调节因子，并降低其抑制作用，最终启动Rho家族成员的激活。我们在此表明，根蛋白的N端区域还与Dbl相互作用，Dbl是Rho家族成员的刺激性GDP/GTP交换蛋白。这种相互作用不影响Dbl刺激Rho亚家族成员RhoA的GDP/GTP交换反应的活性。Dbl不与预先与Rho GDI形成复合物的根蛋白相互作用，并且Rho GDI将Dbl从根蛋白上置换下来。因此，根蛋白通过招募其正负调节因子在Rho家族成员的激活中发挥重要作用。
