The Sch9 protein kinase regulates Hsp90 chaperone complex signal transduction activity in vivo.
Basal and stress-induced synthesis of the components of the highly conserved heat shock protein Hsp90 chaperone complex require the heat shock transcription factor (HSF); Saccharomyces cerevisiae cells expressing the HSF allele HSF(1-583) reversibly arrest growth at 37 degrees C in the G(2)/M phase of the cell cycle due to diminished expression of these components. A suppressor mutant capable of restoring high-temperature growth to HSF(1-583) cells was identified, harboring a disruption of the SCH9 protein kinase gene, homologous to the protein kinase A and protein kinase B/Akt families of mammalian growth control kinases. Loss of Sch9 in HSF(1-583) cells derepresses Hsp90 signal transduction functions as demonstrated by restoration of transcriptional activity by the mammalian glucocorticoid receptor and the heme-dependent transcription factor Hap1, and by enhanced pheromone-dependent signaling through the Ste11 mitogen-activated protein kinase (MAPK). Moreover, Sch9-deficient cells with normal levels of Hsp90 chaperone complex components display hyperactivation of the pheromone response MAPK pathway in the absence of pheromone. These results demonstrate that the evolutionarily conserved function of the Hsp90 chaperone complex as a signal transduction facilitator is modulated by a growth regulatory kinase.
Morano
K A
KA
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
Thiele
D J
DJ
D019757:Carbon-Oxygen Lyases / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011494:Protein Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013489:Suppression, Genetic; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C067168:HSF1 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases; C071569:SCH9 protein kinase; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase