Scgl, the product of the Saccharomyces cerevisiae SCGI (also called GPAI) gene, is homologous to the a subunits of G proteins involved in signal transduction in mammalian cells. Scgl negatively controls the pheromone response pathway in haploid cells. Either pheromonal activation or an scgl null mutation relieves the negative control and leads to an arrest of cell growth in the Gl phase of the cell cycle. Expression of rat Gas was previously shown to complement the growth defect of scgl null mutants while not allowing mating. We have extended this analysis to examine the effects of the short form of Gas (which lacks 15 amino acids present in the long form), Gai2, Gao, and Genes involved in pheromone response and mating that encode a, P, and -y homologs have been identified. The a homolog (Scgl) is encoded by SCGI (10) (also called GPAI;22,23), and the and y subunits (Ste4, Stel8) are encoded by STE4 and STE18, respectively (32) (10,14,22,24).Genetic results indicate that P and -y act downstream of a in the pathway (1,24,32). A model consistent with these results suggests that, in the resting state, the G protein exists as a heterotrimer, a(GDP)PBy (10,14,32