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

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14580661
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Aichi Cancer Center
• Principal Investigator: NAGATA Koh-ichi Aichi Cancer Center Res.Inst., Div.Biochemistry., Setien Head, 発がん制御研究部, 室長 (50252143)
• Project Period (FY): 2002 – 2003
• Keywords: Rho / GEF / Plexin / PDZ / Axon guidance

Research Abstract

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.

Research Products

• [Publications] Driessens, M., Olivo, C., Nagata, K., et al.: "B plexins activate Rho through PDZ-RhoGEF"FEBS Letters. 529. 168-172 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawagir, A., et al.: "Functional significance of the specific sites phosphorylated in desmin at cleavage furrow"Mol.Biol.Cell. 14. 1489-1500 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Goto, H., et al.: "Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process."J.Biol.Chem.. 278. 8526-8530 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nagata, K., et al.: "Filament formation of MSF-A, a mammalian septin, in mammary HMEC cells depends on interactions with microtubules."J.Biol.Chem.. 278. 18538-18543 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yasui, Y., et al.: "Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis."J.Biol.Chem.. (in press). (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Driessens M, Olivo C, Nagata K, Inagaki M: "Collard J : B plexins activate Rho through PDZ-RhoGEF."FEBS Lett.. 529. 168-172 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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 cytokinesis coordinatedly with Rho-kinase."Mol.Biol.Cell. 14. 1489-1500 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Goto H, Yasui Y, Kawajiri A, Nigg AE, Terada Y, Tatsuka M, Nagata K, Inagaki M: "Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process."J.Biol.Chem.. 278. 8526-8530 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagata K, Kawajiri A, Matsui S, Takagishi M, Shiromizu T, Saitoh N, Izawa I, Kiyono T, Itoh J T, Hotani H, Inagaki M: "Filament formation of MSF-A, a mammalian septin, in mammary HMEC cells depends on interactions with Microtubules."J.Biol.Chem.. 278. 18538-18543 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より