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

Author(s): Siekhaus, Daria; Drubin, David G
Article Title: 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 light. 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 Gα. 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.
Keywords: Humans; Mutation; Signal Transduction; Receptors, Cell Surface; Cell Separation; Heterotrimeric GTP-Binding Proteins; RGS Proteins
Journal Title: Nature Cell Biology
Volume: 5
Issue 3
ISSN: 1476-4679
Publisher: Nature Publishing Group  
Date Published: 2003-03-01
Start Page: 231
End Page: 235
DOI: 10.1038/ncb941
Open access: no