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

Rho 特异性 GEF KIAA3 的新型 Rho 激活机制分析

• 批准号: 14580661
• 负责人: NAGATA Koh-ichi
• 金额: $ 2.3万
• 依托单位: Aichi Cancer Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580661/
• 关键词: Rho; GEF; Plexin; PDZ; Axon guidance; 神経突起; プレキシン; セマフォリン4D

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.

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。

项目成果

Yasui, Y., et al.: "Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis."J.Biol.Chem.. (in press). (2004)

Yasui, Y., 等人：“Aurora-B 新发现的位点的自磷酸化对于胞质分裂是不可或缺的。”J.Biol.Chem..（出版中）。

Driessens M, Olivo C, Nagata K, Inagaki M: "Collard J : B plexins activate Rho through PDZ-RhoGEF."FEBS Lett.. 529. 168-172 (2002)

Driessens M、Olivo C、Nagata K、Inagaki M：“Collard J：B 丛蛋白通过 PDZ-RhoGEF 激活 Rho。”FEBS Lett.. 529. 168-172 (2002)

Driessens, M., Olivo, C., Nagata, K., et al.: "B plexins activate Rho through PDZ-RhoGEF"FEBS Letters. 529. 168-172 (2002)

Driessens, M.、Olivo, C.、Nagata, K. 等人：“B 丛蛋白通过 PDZ-RhoGEF 激活 Rho”FEBS Letters。

Yasui, Y., Urano, T., Kawajiri, A., Nagata, K., Tatsuka, M., Saya, H., Furukawa, K., Takahashi, T., Izawa, I., Inagaki, M.: "Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis"J.Biol.Chem.. (in press). (2004)

安井，Y.，浦野，T.，川尻，A.，永田，K.，龙香，M.，Saya，H.，古川，K.，高桥，T.，井泽，I.，稻垣，M.：

Kawajiri A, Yasui Y, Goto H, Tatsuka M, Takahashi M, Nagata K, Inagaki M: "Functional significance of the specific sites phosphorylated in desmin at cleavage furrow : Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokines

Kawajiri A、Yasui Y、Goto H、Tatsuka M、Takahashi M、Nagata K、Inagaki M：“卵裂沟结蛋白中磷酸化特定位点的功能意义：Aurora-B 可能在细胞因子过程中磷酸化并调节 III 型中间丝