Emerging Roles for Regulator of G Protein Signaling 2 in (Patho)physiology

Mol Pharmacol. 2020 Dec;98(6):751-760. doi: 10.1124/molpharm.120.000111. Epub 2020 Sep 23.


Since their discovery in the mid-1990s, regulator of G protein signaling (RGS) proteins have emerged as key regulators of signaling through G protein-coupled receptors. Among the over 20 known RGS proteins, RGS2 has received increasing interest as a potential therapeutic drug target with broad clinical implications. RGS2 is a member of the R4 subfamily of RGS proteins and is unique in that it is selective for Gα q Despite only having an RGS domain, responsible for the canonical GTPase activating protein activity, RGS2 can regulate additional processes, such as protein synthesis and adenylate cyclase activity, through protein-protein interactions. Here we provide an update of the current knowledge of RGS2 function as it relates to molecular mechanisms of regulation as well as its potential role in regulating a number of physiologic systems and pathologies, including cardiovascular disease and central nervous system disorders, as well as various forms of cancer. SIGNIFICANCE STATEMENT: Regulator of G protein signaling (RGS) proteins represent an exciting class of novel drug targets. RGS2, in particular, could have broad clinical importance. As more details are emerging on the regulation of RGS2 in various physiological systems, the potential utility of this small protein in therapeutic development is increasing.

Publication types

  • Review

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Cardiovascular Diseases / pathology
  • Central Nervous System Diseases / pathology
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • Humans
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neoplasms / pathology
  • Protein Biosynthesis / physiology
  • Protein Domains
  • Protein Interaction Maps / physiology
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Rats
  • Signal Transduction / physiology


  • RGS Proteins
  • RGS2 protein, human
  • RGS2 protein, rat
  • Rgs2 protein, mouse
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Adenylyl Cyclases