Suppression of a dominant G-protein beta-subunit mutation in yeast by G alpha protein expression.

SCG1/GPA1, STE4 and STE18 encode the alpha, beta and gamma components of the G protein involved in mating pheromone signal transduction in Saccharomyces cerevisiae. Responses, including G1 arrest and expression of genes such as FUS1, are activated by beta gamma, which is negatively controlled by alpha(GDP). We previously demonstrated that overexpression of Scg1 suppresses responses to alpha factor and that expression of certain hybrids between Scg1 and mammalian G alpha proteins has the same effect and also suppresses growth arrest in an scg1-null mutant. Effects were attributed to sequestration of beta gamma. We now show that effects on growth rate, morphology and FUS1 expression are consistent with this model. The STE4HPL allele causes dominant activation of the response pathway, and is presumed to encode a beta subunit insensitive to control by alpha(GDP). Scg1 overexpression suppresses the growth arrest due to STE4HPL; normal alpha-factor responses and fertility are restored. A model based on sequestration of beta gamma reconciles this result with the apparent paradox that the same level of Scg1 overexpression inhibits responses and mating in wild-type cells. A G alpha i hybrid also restores growth and allows inefficient mating in the STE4HPL strain.