Interaction between the ga subunit of heterotrimeric G(12) protein and Hsp90 is required for G alpha(12) signaling

The G alpha subunit of G(12) protein, one of the heterotrimeric G proteins, regulates diverse and complex cellular responses by transducing signals fr om the cell surface, presumably involving more than one downstream effector . Yeast two-hybrid screening of a human testis cDNA library identified a la rge fragment of Hsp90 as a protein that interacted with G alpha (12). The i nteraction between Ga-12 and Hsp90 was further substantiated by a co-immuno precipitation technique. We have determined that Hsp90 is not required for the interaction of Ga-12 with its binding partners, p115(RhoGEF) and the G beta subunit. Importantly, Hsp90 is required for G alpha (12)-induced serum response element activation, cytoskeletal changes, and mitogenic response. Closely related to G alpha (12), the G alpha (13) subunit did not interact with Hsp90 and did not require functional Hsp90 for serum response element activation. Thus, our results identify a novel signaling module of Ga-12 a nd Hsp90.