Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling

We have examined the role of the mouse Diaphanous-related formin (DRF) Rho GTPase binding proteins, mDia1 and mDia2, in cell regulation. The DRFs are required for cytokinesis, stress fiber formation, and transcriptional activ ation of the serum response factor (SRF). 'Activated' mDia1 and mDia2 varia nts, lacking their GTPase binding domains, cooperated with Rho-kinase or RO CK to form stress fibers but independently activated SRF. Src tyrosine kina se associated and co-localized with the DRFs in endosomes and in mid-bodies of dividing cells. Inhibition of Src also blocked cytokinesis, SRF inducti on by activated DRFs, and cooperative stress fiber formation with active RO CK. Our results show that the DRF proteins couple Rho and Src during signal ing and the regulation of actin dynamics.