PMID: 9529386May 16, 1998Paper

Mechanisms governing the activation and trafficking of yeast G protein-coupled receptors

Molecular Biology of the Cell
C J StefanK J Blumer

Abstract

We have addressed the mechanisms governing the activation and trafficking of G protein-coupled receptors (GPCRs) by analyzing constitutively active mating pheromone receptors (Ste2p and Ste3p) of the yeast Saccharomyces cerevisiae. Substitution of the highly conserved proline residue in transmembrane segment VI of these receptors causes constitutive signaling. This proline residue may facilitate folding of GPCRs into native, inactive conformations, and/or mediate agonist-induced structural changes leading to G protein activation. Constitutive signaling by mutant receptors is suppressed upon coexpression with wild-type, but not G protein coupling-defective, receptors. Wild-type receptors may therefore sequester a limiting pool of G proteins; this apparent "precoupling" of receptors and G proteins could facilitate signal production at sites where cell surface projections form during mating partner discrimination. Finally, rather than being expressed mainly at the cell surface, constitutively active pheromone receptors accumulate in post-endoplasmic reticulum compartments. This is in contrast to other defective membrane proteins, which apparently are targeted by default to the vacuole. We suggest that the quality-control mechanism...Continue Reading

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Citations

Apr 6, 2004·Trends in Pharmacological Sciences·Terry Kenakin
May 7, 2003·Biochemical Pharmacology·Tarja KokkolaJarmo T Laitinen
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Nov 30, 2005·The Journal of Biological Chemistry·Yong-Hun LeeJeffrey M Becker

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