Yeast α‐matching factor receptor‐linked G‐protein signal transduction suppresses Ras‐dependent activity

FEBS Letters

Arkinstall, Stephen J.¹  Payton, Mark A.²  Papasavvas, Savvas G.² 

[1] Department of Biological Chemistry, Glaxo Institute for Molecular Biology, 14 Chemin des Aulx, Case Postale 674, 1228 Plan-les-Ouates, Geneva, Switzerland;Department of Molecular Microbiology, Glaxo Institute for Molecular Biology, 14 Chemin des Aulx, Case Postale 674, 1228 Plan-les-Ouates, Geneva, Switzerland

关键词: Saccharomyces cerevisiae;    α-Mating factor;    Ras;    G-protein;    Cyclic AMP;    IBMX;    3-isobutyl-1-methylxanthine;    G-protein;    GTP-binding regulatory proteins;    IC50;    concentration causing 50% inhibition;   

DOI  :  10.1016/0014-5793(91)80777-Z

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α-mating factor signal transduction pathway. α-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 μM (n = 4)), rapid (maximal within 1–2 min), and displays an absolute requirement for both the α-mating factor receptor (STE2) and associated G-protein β-subunit (STE4). Inhibition appears independent of both phosphodiesterase activation and α-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 p21 ^ras in man. Inhibition of Ras-dependent cyclic AMP formation could also be a key event facilitating responses characteristic of yeast mating.

【 授权许可】

Unknown