Heterotrimeric G proteins act as a molecular switch that conveys signals from G protein-coupled receptors in the cell membrane to intracellular downstream effectors. The G alpha subunits of the G(12) family of heterotrimeric G proteins, defined by G alpha(12) and G alpha(13), have many cellular functions through their specific downstream effectors. On the other hand, regulatory systems of the activity of G alpha(12) and G alpha(13) have not been fully clear. Here, we show that Socius, a previously identified Rho family small GTPase RndI interacting protein, binds directly to G alpha(12) and G alpha(13) through its NH2-terminal region. Socius increased the amounts of GTP-bound active form of G alpha(12) in 293T cells. Furthermore, Socius promotes the G alpha(12)-induced RhoA activation in 293T cells. These results demonstrate that Socius is a novel activator of the G alpha(12) family. (c) 2005 Elsevier Inc. All rights reserved.