DIP (mDia interacting protein) is a key molecule regulating Rho and Rac in a Src-dependent manner

AUTOR(ES)

Meng, Wenxiang

FONTE

Nature Publishing Group

RESUMO

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.

Documentos Relacionados

• Src-dependent Ezrin Phosphorylation in Adhesion-mediated Signaling
• Pyk2- and Src-Dependent Tyrosine Phosphorylation of PDK1 Regulates Focal Adhesions
• Src-dependent STAT-3-mediated Expression of Monocyte Chemoattractant Protein-1 Is Required for 15(S)-Hydroxyeicosatetraenoic Acid-induced Vascular Smooth Muscle Cell Migration*
• Distinct Actions and Cooperative Roles of ROCK and mDia in Rho Small G Protein-induced Reorganization of the Actin Cytoskeleton in Madin–Darby Canine Kidney Cells
• Nef stimulates proliferation of glomerular podocytes through activation of Src-dependent Stat3 and MAPK1,2 pathways