title: Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates.
abstract: BACKGROUND
  In the budding yeast Saccharomyces cerevisiae, components of a single mitogen-activated protein (MAP) kinase pathway transduce two distinct signals, each of which activates an independent developmental programme: peptide mating pheromones initiate the mating response, whereas nutrient limitation initiates filamentous growth. One of the MAP kinases in this pathway, Fus3, triggers mating but antagonizes filamentous growth, while the other, Kss 1, preferentially triggers filamentous growth. Both kinases activate the same transcription factor, Ste 12, which can stimulate gene expression specific to each of the developmental programmes. The precise mechanism by which these MAP kinases activate Ste 12, however, is not clear.
  
  
  RESULTS
  Two newly identified proteins, Rst 1 and Rst 2 (also known as Dig1 and Dig2), were found to associate physically with Fus3 and Ste12. Rst1 and Rst2 were prominent substrates in kinase reactions of Fus3 immune complexes from pheromone-treated cells. Association of Fus3 with Ste12 required Rst1 and Rst2, and activation of Fus3 by pheromone caused release of Ste12 from the Fus3 complex. Although rst1 and rst2 single mutants had no obvious phenotype, both filamentous growth and mating-specific gene expression were constitutive in rst1 rst2 double mutants. The phenotype of rst1 rst2 cells required Ste12 function, but did not require the function of upstream kinases. Consistent with Rst1 and Rst2 having a role in Ste12 regulation, both proteins were localized to the nucleus.
  
  
  CONCLUSIONS
  Rst1 and Rst2 repress the mating and filamentous growth responses of S. cerevisiae by directly inhibiting Ste12. Activation of Fus3 or Kss1 may cause phosphorylation-dependent release of Ste12 from Rst1/Rst2 and thereby activate Ste12-dependent transcription.
authors.affiliation: Programme in Molecular Biology and Cancer Samuel Lunenfeld Research Institute Mount Sinai Hospital 600 University Avenue, Toronto, Canada M5G 1X5.
authors.forename: K
authors.initials: K
authors.lastname: Tedford
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Sa
authors.forename: K
authors.initials: K
authors.lastname: Stevens
authors.forename: M
authors.initials: M
authors.lastname: Tyers
mesh_terms: D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000378:metabolism*; D005982:Glutathione Transferase; D000072235:Mating Factor; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D010452:Peptide Biosynthesis; D010455:Peptides; D010675:Pheromones / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C102297:DIG1 protein, S cerevisiae; C102298:DIG2 protein, S cerevisiae; D005656:Fungal Proteins; D010455:Peptides; D010675:Pheromones; D011993:Recombinant Fusion Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000072235:Mating Factor; D005982:Glutathione Transferase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C075580:FUS3 protein, S cerevisiae; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases