The first CH domain of affixin activates Cdc42 and Rac1 through αPIX, a Cdc42/Rac1‐specific guanine nucleotide exchanging factor

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 9; no. 3; pp. 193 - 204
• Main Authors: Mishima, Wataru, Suzuki, Atsushi, Yamaji, Satoshi, Yoshimi, Ryusuke, Ueda, Atsuhisa, Kaneko, Takeshi, Tanaka, Junko, Miwa, Yoshihiro, Ohno, Shigeo, Ishigatsubo, Yoshiaki
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing, Ltd 01.03.2004
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/j.1356-9597.2004.00717.x

Rho GTPases, Cdc42 and Rac1, play pivotal roles in cell migration by efficiently integrating cell‐substrate adhesion and actin polymerization. Although it has been suggested that integrins stimulate these Rho GTPases via some of integrin binding proteins such as focal adhesion kinase (FAK) and paxillin, the precise molecular mechanism is largely unknown. In this study, we showed that the over‐expression of RP1 corresponding to the first CH domain (CH1) of affixin, an integrin‐linked kinase (ILK)‐binding protein, induced a significant actin reorganization in MDCK cells by activating Cdc42/Rac1. Affixin full length and RP1 co‐immunoprecipitated with αPIX, a Cdc42/Rac1‐specific guanine nucleotide exchanging factor (GEF), and they co‐localized at the tips of lamellipodia in motile cells. The involvement of αPIX in the RP1‐induced Cdc42 activation was demonstrated by the significant dominant negative effect of a point mutant of αPIX, αPIX (L383R, L384S), lacking GEF activity. Our data strongly support that ILK and affixin provide a novel signalling pathway that links integrin signalling to Cdc42/Rac1 activation.