2009 Fiscal Year Final Research Report

Studies on the role of FiliGAP (RacGAP) in cell migration, adhesion, and polarization.

Research Project

Project/Area Number	19370081
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Cell biology
Research Institution	Kitasato University
Principal Investigator	OHTA Yasutaka Kitasato University, 理学部, 教授 (90192517)
Project Period (FY)	2007 – 2009
Keywords	細胞運動 / 細胞接着 / 細胞極性 / 低分子量GTP結合タンパク質 / 細胞骨格
Research Abstract	FilGAP is a newly-identified RhoGAP, which activity is specific for Rac. I have studied the mechanism of regulation of FilGAP activity in vivo. (1) I have identified protein factors, which binds specifically to de-phosphorylated FilGAP. (2) FilGAP is phosphorylated at 6 amino acid residues by ROCK. I have identified Serine 402 as a crucial phosphorylation site to activate FilGAP. (3) The PH domain of FilGAP binds phospholipid PIP3. However, I found that the activity of FilGAP is not dependent on PIP3. Activated small GTPase Arf6 binds the PH domain of FilGAP and stimulates its GAP activity. This suggests FilGAP is involved in the Arf6-dependent regulation of Rac. FilGAP therefore regulates Rac downstream of RhoA and Arf6.