Yeast Alpha-Mating Factor Receptor-Linked G-protein Signal Transduction Suppresses Ras-dependent Activity

FEBS Lett. 1991 Jun 17;284(1):123-8. doi: 10.1016/0014-5793(91)80777-z.

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.

MeSH terms

  • Cyclic AMP / metabolism
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Genes, ras*
  • Kinetics
  • Mating Factor
  • Peptides / metabolism
  • Pheromones / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, Mating Factor
  • Receptors, Peptide*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Signal Transduction*
  • Transcription Factors / metabolism

Substances

  • Peptides
  • Pheromones
  • Receptors, Cell Surface
  • Receptors, Mating Factor
  • Receptors, Peptide
  • Transcription Factors
  • Mating Factor
  • Cyclic AMP
  • GTP-Binding Proteins