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 identified mammalian proteins that activate heterotrimeric G-protein signaling pathways in a receptor-independent fashion. One of the identified activators, termed AGS1 (for activator of G-protein signaling), is a human Res-related G-protein that defines a distinct subgroup of the Res superfamily. Expression of AGS1 in yeast and in mammalian cells results in specific activation 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 functioning as a direct guanine nucleotide exchange factor for G alpha(i)/G alpha(o). AGS1 thus presents a unique mechanism for signal integration via heterotrimeric G-protein signaling pathways.