DIAPH1 is activated by binding of the DIAPH1 dimer to GTP-bound (active) RHOA. Binding to RHOA releaves the autoinhibitory interaction of DIAPH1 FH3 and DAD domains (Otomo et al. 2005). Phosphorylation of RHOA at serine residue S188 may be required for RHOA binding to DIAPH1 (Li and Sewer 2010). The interaction between RHOA and DIAPH1 may also be positively regulated by PI3K signaling (Gao et al. 2009).