Constitutive Mutants of the Protein Kinase STE11 Activate the Yeast Pheromone Response Pathway in the Absence of the G Protein

STE4 encodes the beta-subunit of a heterotrimeric guanine nucleotide-binding protein (G protein) that is an early and essential component of the pheromone signal transduction pathway. From a ste4 deletion strain we have isolated both dominant and recessive suppressors that show increased transcription of pheromone responsive genes and have regained the ability to mate, albeit at a low level. Each of these suppressor mutations suppresses ste4 and ste5 deletions but not deletions in STE7, STE11, or STE12. Among the dominant mutations, we have identified two alleles of STE11, a gene that encodes a protein kinase activity essential for mating. One allele contains an alteration in the putative regulatory domain of the protein kinase; the second allele has an alteration in the catalytic site. In strains carrying these mutations, a second protein kinase required for mating, STE7, becomes hyperphosphorylated, just as it does in wild-type cells treated with pheromone. Thus, a protein kinase cascade appears to be an essential feature of the response pathway and probably connects the receptor/G protein to an identified transcription factor, STE12.