Emerging roles for RGS proteins in cell signalling

Regulators of G-protein signalling (RGS proteins) are a family of highly di verse, multifunctional signalling proteins that share a conserved 120 amino acid domain (RGS domain). RGS domains bind directly to activated Ga: subun its and a ct as GTPase-activating proteins (GAPs) to attenuate and/or modul ate hormone and neurotransmitter receptor-initiated signalling by both G al pha-GTP and G beta gamma. Apart from this structural domain, which is share d by all known RGS proteins, these proteins differ widely in their overall size and amino acid identity and possess a remarkable variety of structural domains and motifs. These biochemical features impart signalling functions and/or enable RGS proteins to interact with a growing list of unexpected p rotein-binding partners with diverse cellular roles. New appreciation for t he broader cellular functions of RGS proteins challenges established models of G-protein signalling and serves to identify these proteins as central p articipants in receptor signalling and cell physiology.