Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling

We describe genetic screens in Saccharomyces cerevisiae designed to identif y mammalian nonreceptor modulators of G-protein signaling pathways. Strains lacking a pheromone-responsive G-protein coupled receptor and expressing a mammalian-yeast G alpha hybrid protein were made conditional for growth up on either pheromone pathway activation (activator screen) or pheromone path way inactivation (inhibitor screen). Mammalian cDNAs that conferred plasmid -dependent growth under restrictive conditions were identified. One of the cDNAs identified from the activator screen, a human Ras-related G protein t hat we term AGS1 (for activator of G-protein signaling), appears to functio n by facilitating guanosine triphosphate (GTP) exchange on the heterotrimer ic G alpha. A cDNA product identified from the inhibitor screen encodes a p reviously identified regulator of G-protein signaling, human RGS5.