title: RGS proteins: G protein-coupled receptors meet their match.
abstract: Many drugs act on receptors coupled to heterotrimeric G proteins. Historically, drug discovery has focused on agents that bind to the receptors and either stimulate or inhibit the receptor-initiated signal. This is an approach that is both direct and logical, and has proven extremely fruitful in the past. However, as our understanding of G-protein signaling has increased, novel opportunities for drug development have emerged. RGS proteins are multifunctional GTPase-accelerating proteins that inactivate G-protein signaling pathways. GTPase-accelerating protein activity is a general feature of RGS proteins, and serves to facilitate the inactivation of the G protein rather than the receptor. Thus, agents that bind and inhibit RGS proteins could modulate endogenous neurotransmitter and hormone signaling, in a manner analogous to neurotransmitter uptake inhibitors. Here we discuss the potential of RGS proteins as drug targets.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Chasse
authors.forename: Henrik G
authors.initials: HG
authors.lastname: Dohlman
mesh_terms: D000818:Animals; D006801:Humans; D020710:RGS Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D020710:RGS Proteins; D043562:Receptors, G-Protein-Coupled