Specific in vivo binding of activator of G protein signalling 1 to the Gβ1 subunit

Activator of G protein signalling 1 (AGS1) is a Ras-like protein that affects signalling through heterotrimeric G proteins. Previous in vitro studies suggest that AGS1 can bind to Gα-GDP subunits and promote nucleotide exchange, leading to activation of intracellular signalling pathways. This model is consistent with in vivo evidence demonstrating that AGS1 activates both Gα- and Gβγ-dependent pathways in the absence of ligand. However, it does not easily explain how AGS1 blocks Gβγ-dependent, but not Gα-dependent, signalling following receptor activation. We have used yeast two hybrid analysis and co-immunoprecipitation studies in mammalian cells to demonstrate a direct interaction between AGS1 and the Gβ1 subunit of heterotrimeric G proteins. The interaction is specific for Gβ1 and involves the cationic region of AGS1 and the C-terminal region of Gβ1. Possible implications of this novel interaction for the activity of AGS1 are discussed.