Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein α subunit Gα13

Signal transduction pathways that mediate activation of serum response factor (SRF) by heterotrimeric G protein Lu subunits were characterized in transfection systems. G alpha q, G alpha 12, and Ga13, but not G alpha i, activate SRF through RhoA. When G alpha q, alpha 12, or alpha 13 were coexpressed with a Rho-specific guanine nucleotide exchange factor GEF115, G alpha 13, but not G alpha q or G alpha 12, showed synergistic activation of SRF with GEF115. The synergy between G alpha 13 and GEF115 depends on the N-terminal part of GEF11S, and there was no synergistic effect between G alpha 13 and another Rho-specific exchange factor Lbc, In addition, the Dbl-homology (DH)-domain-deletion mutant of GEF115 inhibited G alpha 13- and G alpha 12-induced, but not GEF115 itself- or G alpha q-induced, SRF activation. The DH-domain-deletion mutant also suppressed thrombin and lysophosphatidic acid-induced SRF activation in NIH 3T3 cells, probably by inhibition of G alpha 12/13. The N-terminal part of GEF115 contains a sequence motif that is homologous to the regulator of G protein signaling (RGS) domain of RGS12. RGS12 can inhibit both G alpha 12 and G alpha 13, Thus, the inhibition of Gcu12/13 by the DH deletion mutant may be due to the RGS activity of the mutant, The synergism between G alpha 13 and GEF115 indicates that GEF115 mediates G alpha 13-induced activation of Rho and SRF.