Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant

Nat Cell Biol. 2003 Mar;5(3):231-5. doi: 10.1038/ncb941.


Tripartite G-protein-coupled receptors (GPCRs) represent one of the largest groups of signal transducers, transmitting signals from hormones, neuropeptides, odorants, food and light. Ligand-bound receptors catalyse GDP/GTP exchange on the G-protein alpha-subunit (Galpha), leading to alpha-GTP separation from the betagamma subunits and pathway activation. Activating mutations in the receptors or G proteins underlie many human diseases, including some cancers, dwarfism and premature puberty. Regulators of G-protein signalling (RGS proteins) are known to modulate the level and duration of ligand-induced signalling by accelerating the intrinsic GTPase activity of the Galpha subunit, and thus reformation of the inactive GDP-bound Galpha. Here we find that even in the absence of receptor, mutation of the RGS family member Sst2 (refs 6-9) permits spontaneous activation of the G-protein-coupled mating pathway in Saccharomyces cerevisiae at levels normally seen only in the presence of ligand. Our work demonstrates the occurrence of spontaneous tripartite G-protein signalling in vivo and identifies a requirement for RGS proteins in preventing such receptor-independent activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Separation
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Mutation*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction*


  • RGS Proteins
  • Receptors, Cell Surface
  • Heterotrimeric GTP-Binding Proteins