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

Abstract

Tripartite G-protein-coupled receptors (GPCRs) represent one of the largest groups of signal transducers, transmitting signals from hormones, neuropeptides, odorants, food and light1,2. Ligand-bound receptors catalyse GDP/GTP exchange on the G-protein α-subunit (Gα), leading to α-GTP separation from the βγ 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 Gα subunit, and thus reformation of the inactive GDP-bound Gα3,4,5. 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 occurence of spontaneous tripartite G-protein signalling in vivo and identifies a requirement for RGS proteins in preventing such receptor-independent activation.

Cite this article

Siekhaus, D., Drubin, D. Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. Nat Cell Biol 5, 231–235 (2003). https://doi.org/10.1038/ncb941

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