Anayses of a novel Rho-activation mechanism by Rho-specific GEF, KIAA3

神经丛蛋白是排斥性轴突引导分子信号素的受体。以前，我们已经证明Plexin-B1与激活的RAC结合，但Plexin-B1的聚集导致Rho激活，导致应力纤维形成。利用酵母双杂交系统，我们发现B丛蛋白的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。共表达显性负性PDZ-Rhogef的丛蛋白-B1的羧基末端氨基酸的突变取消了丛蛋白-B1引起应力纤维形成的能力。我们的结果表明，PDZ-Rhogef在B丛蛋白介导的Rho/Rho激酶信号的激活中发挥了作用，这与轴突引导和细胞迁移的调节有关。

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 of 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.