Cell movement is driven by the coordinated regulation of cytoskeletal 
reorganization through Rho GTPases downstream of integrin and growth-factor 
receptor signaling. We have reported that mDia, a target protein of Rho, 
interacts with Src and DIP. Here we show that DIP binds to p190RhoGAP and Vav2, 
and that DIP is phosphorylated by Src and mediates the phosphorylation of 
p190RhoGAP and Vav2 upon EGF stimulation. When endogenous DIP was inhibited by 
expressing dominant-negative mutants of DIP or siRNA, phosphorylation of 
p190RhoGAP and Vav2 upon EGF stimulation was diminished, and EGF-induced actin 
organization, distribution of p190RhoGAP and Vav2, and cell movement were 
affected. Therefore, DIP seems to transfer the complex of the three proteins 
from cytosol to beneath the membrane, and the three proteins, in turn, can be 
phosphorylated by Src. DIP inactivated Rho and activated Rac following EGF 
stimulation in the membrane fraction. Thus, DIP acts as a regulatory molecule 
causing Src kinase-dependent feedback modulation of Rho GTPases downstream of 
Rho-mDia upon EGF stimulation, and plays an important role in cell motility.