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 cyclicAMP formation. Mating pheromone inhibits RAS-linked adenylyl cyclase activation and this is dependent upon the α-factor receptor (STE2) and its associated G-protein β-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 Gprotein α-subunit encoded by GPA2. α-mating factor effects also involve a specific suppression of normal RAS2 activity as the constitutively activated mutant RAS2va119 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. © 1992 Academic Press, Inc.