Regulation of the yeast pheromone response pathway by G protein subunits

The yeast GPA1, STE4, and STE18 genes encode proteins homologous to the respective α, β and γ subunits of the mammalian G protein complex which appears to mediate the response to mating pheromones. Overexpression of the STE4 protein by the galactose-inducible GAL1 promoter caused activation of the pheromone response pathway which resulted in cell-cycle arrest in late G1 phase and induction of the FUS1 gene expression, thereby suppressing the sterility of the receptor-less mutant Δste2. Disruption of STE18, in turn, suppressed activation of the pheromone response induced by overexpression of STE4, suggesting that the STE18 product is required for the STE4 action. However, overexpression of both the STE4 and STE18 proteins did not generate a stronger pheromone response than overexpression of STE4 in the presence of wild-type levels of STE18. These results suggest that the β subunit is the limiting component for the pheromone response and support the idea that β and γ subunits act as a positive regulator. Furthermore, overexpression of GPA 1 prevented cell-cycle arrest but not FUS1 induction mediated by overexpression of STE4. This implies that the α subunit acts as a negative regulator presumably through interacting with β and γ subunits in the mating pheromone signaling pathway.