Ras homologue enriched in striatum (Rhes) is a small monomeric G protein which functions in a variety of cellular processes, including attenuation of G protein-coupled receptor (GPCR) signalling. There have been many studies into the effects of Rhes, but there is no molecular information about how Rhes might bring about these effects. Rhes shares striking sequence homology to AGS1 (activator of G protein signalling 1) and we considered whether the two proteins function in similar ways. AGS1 binds to the Gbeta1 subunit of heterotrimeric G proteins and we have used yeast two-hybrid studies to show that Rhes binds selectively to Gbeta1, Gbeta2 and Gbeta3 subunits. Binding to the Gbeta subunits involves the cationic regions of AGS1 and Rhes, and we used Rhes-AGS1 chimeras to show that their different cationic regions determine the Gbeta-specificity of the interactions. Possible implications of this interaction for the activity of Rhes are discussed.
