Involvement of small GTPase Rho family signaling pathways in diseases.

2014 Fiscal Year Final Research Report

• Project/Area Number: 23590357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: AMANO Mutsuki 名古屋大学, 医学(系)研究科(研究院), 准教授 (90304170)
• Co-Investigator(Kenkyū-buntansha): KAIBUCHI Kozo 名古屋大学, 大学院医学系研究科, 教授 (00169377)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: 細胞内シグナル伝達 / リン酸化 / キナーゼ / プロテオミクス

Outline of Final Research Achievements

In this study, we focused on the analysis of protein kinases downstream of Rho family small GTPases as therapeutic targets. We developed the novel substrate screening method based on the interactome analysis. By this method, a number of candidate substrates were identified for several kinases including Rho-kinase, PKN, and aPKC. We identified tumor suppressor protein Scrib and cardiomyopathy-related gene products such as CARP and MYL2 as novel Rho-kinase substrates. We identified phosphorylation sites, and analyzed the modes of action for Scrib and CARP upon the phosphorylation by Rho-kinase. We also found that PKA phosphorylates Rho-kinase, suggesting the crosstalk between PKA and Rho-kinase.

Free Research Field

生化学、分子生物学、細胞生物学