The dynamic role of regulator of G-protein signalling (RGS) proteins in partial agonism.

Abstract

G-protein-coupled receptors (GPCRs) are important targets of pharmaceutical research. A subclass of GPCR ligands act as partial agonists, meaning that they elicit a submaximal response as compared to a full agonist. Differences in the regulation of heterotrimeric G-proteins are thought to underlie the lower activation efficacy of partial agonists. These heterotrimeric G-proteins are reciprocally regulated by guanine nucleotide exchange factors (GEFs) and a family of GTPase-activating proteins known as regulators of G-protein signalling (RGS). Although differences in GEF efficiency have been shown to underlie the submaximal response of certain partial agonists, the role of RGS proteins in this mechanism has not been assessed.