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FEBS Lett. 1991 Jun 17;284(1):123-8.

Yeast alpha-mating factor receptor-linked G-protein signal transduction suppresses Ras-dependent activity.

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1
Department of Biological Chemistry, Glaxo Institute for Molecular Biology, Geneva, Switzerland.

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.

PMID:
1647971
[Indexed for MEDLINE]
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