Title: | The Sch9 protein kinase regulates Hsp90 chaperone complex signal transduction activity in vivo |
Address: | "Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA" |
ISSN/ISBN: | 0261-4189 (Print) 1460-2075 (Electronic) 0261-4189 (Linking) |
Abstract: | "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" |
Keywords: | "Carbon-Oxygen Lyases/genetics Cell Cycle/genetics *DNA-(Apurinic or Apyrimidinic Site) Lyase DNA-Binding Proteins/genetics/metabolism Fungal Proteins/metabolism Gene Expression Regulation, Fungal HSP90 Heat-Shock Proteins/*metabolism Heat-Shock Proteins/g;" |
Notes: | "MedlineMorano, K A Thiele, D J eng 1F32 GM19195-01/GM/NIGMS NIH HHS/ 5T32CA09676-06/CA/NCI NIH HHS/ R01 GM59911/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 1999/11/02 EMBO J. 1999 Nov 1; 18(21):5953-62. doi: 10.1093/emboj/18.21.5953" |