RGS proteins: G protein-coupled receptors meet their match

Assay Drug Dev Technol. 2003 Apr;1(2):357-64. doi: 10.1089/154065803764958649.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • RGS Proteins / drug effects*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • RGS Proteins
  • Receptors, G-Protein-Coupled