Novobiocin activates the mating response in yeast through the alpha-pheromone receptor, Ste2p.
In a previous publication we reported the isolation of several yeast mutants sensitive to the coumarin drug novobiocin. Here we characterise the wild-type gene (NBS5), obtained by rescuing a novobiocin-sensitive nbs5 strain to natural novobiocin resistance. We show that nbs5 is allelic to the previously characterised gene sst2, conferring super-sensitivity to the mating pheromones. Although nbs5/sst2 cells of both mating types are super-sensitive to the opposite mating pheromone, only cells of mating-type a are sensitive to novobiocin. We show that the entire effect of the drug is mediated through Ste2p, the alpha-pheromone receptor. Thus, novobiocin is a functional agonist of Ste2p, and may identify a potentially useful interaction between coumarin drugs and the family of G-protein-coupled receptors.
Pocklington
M J
MJ
Department of Genetics, University of Leicester, UK.
Orr
E
E
D005816:Genetic Complementation Test; D000072235:Mating Factor; D009675:Novobiocin / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics* / Q000502:physiology; D010957:Plasmids; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000819:agonists* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors
D010455:Peptides; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D014157:Transcription Factors; D009675:Novobiocin; D000072235:Mating Factor