title: Yeast alpha-mating factor receptor-linked G-protein signal transduction suppresses Ras-dependent activity.
abstract: Homologues of mammalian Ras conserved in Saccharomyces cerevisiae mediate glucose-stimulated cyclic AMP formation and we used this response to test for regulation of yeast Ras activity by the alpha-mating factor signal transduction pathway. alpha-Mating factor suppresses glucose-stimulated cyclic AMP formation by up to 57 +/- 12.6% (n = 5) and similar inhibition was observed in four different yeast strains (MATa cells). Moreover, this response is potent (IC50 = 0.14 +/- 0.19 microM (n = 4)), rapid (maximal within 1-2 min), and displays an absolute requirement for both the alpha-mating factor receptor (STE2) and associated G-protein beta-subunit (STE4). Inhibition appears independent of both phosphodiesterase activation and alpha-mating factor-stimulated cytoplasmic alkalinization. Also, basal cyclic AMP levels are unaffected by pheromone. This is the first demonstration that a cell-surface receptor linked to a heterotrimeric G-protein can suppress Ras-dependent activity and could provide important insight into mechanisms controlling p21ras in man. Inhibition of Ras-dependent cyclic AMP formation could also be a key event facilitating responses characteristic of yeast mating.
authors.affiliation: Department of Biological Chemistry, Glaxo Institute for Molecular Biology, Geneva, Switzerland.
authors.forename: S J
authors.initials: SJ
authors.lastname: Arkinstall
authors.forename: S G
authors.initials: SG
authors.lastname: Papasavvas
authors.forename: M A
authors.initials: MA
authors.lastname: Payton
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D011905:Genes, ras; D007700:Kinetics; D000072235:Mating Factor; D010455:Peptides / Q000378:metabolism; D010675:Pheromones / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D010455:Peptides; D010675:Pheromones; D011956:Receptors, Cell Surface; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D014157:Transcription Factors; D000072235:Mating Factor; D000242:Cyclic AMP; D019204:GTP-Binding Proteins