The Sch9 protein kinase regulates Hsp90 chaperone complex signal transduction activity in vivo

Basal and stress-induced synthesis of the components of the highly conserve d heat shock protein Hsp90 chaperone complex require the heat shock transcr iption factor (HSF); Saccharomyces cerevisiae cells expressing the HSF alle le 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 suppr essor mutant capable of restoring high-temperature growth to HSF(1-583) cel ls was identified, harboring a disruption of the SCH9 protein kinase gene, homologous to the protein kinase A and protein kinase B/Akt families of mam malian growth control kinases, Loss of Sch9 in HSF(1-583) cells derepresses Hsp90 signal transduction functions as demonstrated by restoration of tran scriptional activity by the mammalian glucocorticoid receptor and the heme- dependent transcription factor Hap1, and by enhanced pheromone-dependent si gnaling through the Ste11 mitogen-activated protein kinase (MAPK), Moreover , Sch9-deficient cells with normal levels of Hsp90 chaperone complex compon ents display hyperactivation of the pheromone response MAPK pathway in the absence of pheromone. These results demonstrate that the evolutionarily con served function of the Hsp90 chaperone complex as a signal transduction fac ilitator is modulated by a growth regulatory kinase.