Yeast alpha-mating factor receptor and G-protein-linked adenylyl cyclase inhibition requires RAS2 and GPA2 activities.
Saccharomyces cerevisiae expresses two RAS gene products (RAS1 and RAS2) highly homologous to mammalian p21ras which mediate glucose-stimulated cyclic-AMP formation. Mating pheromone inhibits RAS-linked adenylyl cyclase activation and this is dependent upon the alpha-factor receptor (STE2) and its associated G-protein beta-subunit (STE4). We now show that this pheromone effect is independent of mating pathway signalling components "downstream" of STE4 but displays an absolute requirement for an additional G-protein alpha-subunit encoded by GPA2. alpha-mating factor effects also involve a specific suppression of normal RAS2 activity as the constitutively activated mutant RAS2vall9 as well as wild type. RAS1 are insensitive to inhibition. Interaction between GPA2, STE4-STE18, RAS2 and adenylyl cyclase in yeast could give important insight into signalling pathways controlling normal and oncogenic p21ras activity in man.
Papasavvas
S
S
Glaxo Institute for Molecular Biology, Chemin des Aulx, Geneva, Switzerland.
Arkinstall
S
S
Reid
J
J
Payton
M
M
D000067956:Adenylyl Cyclase Inhibitors; D000242:Cyclic AMP / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D011905:Genes, ras; D005816:Genetic Complementation Test; D005838:Genotype; D007700:Kinetics; D046911:Macromolecular Substances; D000072235:Mating Factor; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D010675:Pheromones / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism; D018631:ras Proteins
D000067956:Adenylyl Cyclase Inhibitors; D005656:Fungal Proteins; D046911:Macromolecular Substances; D010455:Peptides; D010675:Pheromones; D011956:Receptors, Cell Surface; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000072235:Mating Factor; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; C489014:RAS1 protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins