Coupling of cell identity to signal response in yeast: interaction between the alpha 1 and STE12 proteins

In Saccharomyces cerevisiae, the STE12 protein mediates transcriptional induction of cell type-specific genes in response to pheromones. STE12 binds in vitro to the pheromone response elements (PREs) present in the control region of a-specific genes. STE12 is also required for transcription of alpha-specific genes, but there is no evidence that it binds directly to these genes. Instead, the MAT alpha-encoded protein alpha 1 and the MCM1 product bind to the DNA element that is responsible for alpha-specific and a-factor-inducible expression. To explore the role of STE12 in the pheromone induction of alpha-specific genes, we cloned STE12 and MAT alpha 1 homologs from the related yeast Kluyveromyces lactis. The K. lactis STE12 protein did not cooperate with the S. cerevisiae alpha 1 protein to promote the overall mating process or the induction of transcription of an alpha-specific gene. However, introduction of both K. lactis STE12 along with K. lactis alpha 1 did restore mating, suggesting that an interaction between STE12 and alpha 1 is important for alpha-specific gene activation. We also show that bacterially expressed STE12 and alpha 1 are able to form a complex in vitro. Thus, we demonstrate a coupling in alpha cells between a protein functioning in cell identity, alpha 1, with a protein responsive to the pheromone-induced signal STE12.