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

D.E. Siekhaus, D. Drubin, Nature Cell Biology 5 (2003) 231–235.

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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.
Publishing Year
Date Published
2003-03-01
Journal Title
Nature Cell Biology
Volume
5
Issue
3
Page
231 - 235
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Siekhaus DE, Drubin D. Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. Nature Cell Biology. 2003;5(3):231-235. doi:10.1038/ncb941
Siekhaus, D. E., & Drubin, D. (2003). Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. Nature Cell Biology, 5(3), 231–235. https://doi.org/10.1038/ncb941
Siekhaus, Daria E, and David Drubin. “Spontaneous Receptor-Independent Heterotrimeric G-Protein Signalling in an RGS Mutant.” Nature Cell Biology 5, no. 3 (2003): 231–35. https://doi.org/10.1038/ncb941.
D. E. Siekhaus and D. Drubin, “Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant,” Nature Cell Biology, vol. 5, no. 3, pp. 231–235, 2003.
Siekhaus DE, Drubin D. 2003. Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant. Nature Cell Biology. 5(3), 231–235.
Siekhaus, Daria E., and David Drubin. “Spontaneous Receptor-Independent Heterotrimeric G-Protein Signalling in an RGS Mutant.” Nature Cell Biology, vol. 5, no. 3, Nature Publishing Group, 2003, pp. 231–35, doi:10.1038/ncb941.

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