Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave of Rac1 activation in the process of cell migration.

ABSTRACT: Immense previous efforts have elucidated the core machinery in cell migration, actin remodeling regulated by Rho family small GTPases including RhoA, Cdc42, and Rac1; however, the spatiotemporal regulation of these molecules remains largely unknown. Here, we report that EGF induces biphasic Rac1 activation in the process of cell migration, and UTKO1, a cell migration inhibitor, inhibits the second EGF-induced wave of Rac1 activation but not the first wave. To address the regulation mechanism and role of the second wave of Rac1 activation, we identified 14-3-3? as a target protein of UTKO1 and also showed that UTKO1 abrogated the binding of 14-3-3? to Tiam1 that was responsible for the second wave of Rac1 activation, suggesting that the interaction of 14-3-3? with Tiam1 is involved in this event. To our knowledge, this is the first report to use a chemical genetic approach to demonstrate the mechanism of temporal activation of Rac1.

SUBMITTER: Kobayashi H 

PROVIDER: S-EPMC3234750 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature