Activation of heterotrimeric G-protein signaling by a Ras-related protein - Implications for signal integration

Utilizing a functional screen in the yeast Saccharomyces cerevisiae we iden tified mammalian proteins that activate heterotrimeric G-protein signaling pathways in a receptor-independent fashion. One of the identified activator s, termed AGS1 (for activator of G-protein signaling), is a human Res-relat ed G-protein that defines a distinct subgroup of the Res superfamily. Expre ssion of AGS1 in yeast and in mammalian cells results in specific activatio n of G alpha(i)/G alpha(o) heterotrimeric signaling pathways. In addition, the in vivo and in vitro properties of AGS1 are consistent with it function ing as a direct guanine nucleotide exchange factor for G alpha(i)/G alpha(o ). AGS1 thus presents a unique mechanism for signal integration via heterot rimeric G-protein signaling pathways.