Driessens Mariette H E, Olivo Cristina, Nagata Koh-ichi, Inagaki Masaki, Collard John G
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
FEBS Lett. 2002 Oct 9;529(2-3):168-72. doi: 10.1016/s0014-5793(02)03323-9.
Plexins are receptors for the repulsive axon guidance molecules semaphorins. Previously, we have shown that plexin-B1 binds activated Rac, but that clustering of plexin-B1 causes Rho activation, resulting in stress fiber formation. Using the yeast two-hybrid system, we found that the C-terminus of B plexins interacted directly with Rho-specific exchange factors, via their PDZ domain. Mutation of the carboxy-terminal amino acids of plexin-B1 or coexpression of a dominant negative PDZ-RhoGEF abrogated the ability of plexin-B1 to cause stress fiber formation. Our results demonstrate a role for PDZ-RhoGEF in B plexin-mediated activation of Rho/Rho kinase signaling, implicated in the regulation of axon guidance and cell migration.
丛状蛋白是排斥性轴突导向分子信号素的受体。此前，我们已经表明丛状蛋白-B1与活化的Rac结合，但丛状蛋白-B1的聚集会导致Rho活化，从而导致应力纤维形成。利用酵母双杂交系统，我们发现B类丛状蛋白的C末端通过其PDZ结构域与Rho特异性交换因子直接相互作用。丛状蛋白-B1羧基末端氨基酸的突变或显性负性PDZ-RhoGEF的共表达消除了丛状蛋白-B1引起应力纤维形成的能力。我们的结果证明了PDZ-RhoGEF在B类丛状蛋白介导的Rho/Rho激酶信号激活中的作用，这与轴突导向和细胞迁移的调节有关。
