Hsp90 is required for pheromone signaling in yeast.
The heat-shock protein 90 (Hsp90) is a cytosolic molecular chaperone that is highly abundant even at normal temperature. Specific functions for Hsp90 have been proposed based on the characterization of its interactions with certain transcription factors and kinases including Raf in vertebrates and flies. We therefore decided to address the role of Hsp90 for MAP kinase pathways in the budding yeast, an organism amenable to both genetic and biochemical analyses. We found that both basal and induced activities of the pheromone-signaling pathway depend on Hsp90. Signaling is defective in strains expressing low levels or point mutants of yeast Hsp90 (Hsp82), or human Hsp90beta instead of the wild-type protein. Ste11, a yeast equivalent of Raf, forms complexes with wild-type Hsp90 and depends on Hsp90 function for accumulation. For budding yeast, Ste11 represents the first identified endogenous "substrate" of Hsp90. Moreover, Hsp90 functions in steroid receptor and pheromone signaling can be genetically separated as the Hsp82 point mutant T525I and the human Hsp90beta are specifically defective for the former and the latter, respectively. These findings further corroborate the view that molecular chaperones must also be considered as transient or stable components of signal transduction pathways.
Louvion
J F
JF
Département de Biologie Cellulaire, Université de Genève Sciences III, CH-1211 Genève 4, Switzerland.
Abbas-Terki
T
T
Picard
D
D
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002453:Cell Cycle; D005656:Fungal Proteins / Q000096:biosynthesis / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000072235:Mating Factor; D020929:Mitogen-Activated Protein Kinase Kinases; D016296:Mutagenesis; D010455:Peptides / Q000378:metabolism*; D010675:Pheromones / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005656:Fungal Proteins; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010455:Peptides; D010675:Pheromones; C080321:STE5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C071596:ste11 protein, S pombe; D000072235:Mating Factor; D011494:Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases