title: The molecular chaperone Sse1 and the growth control protein kinase Sch9 collaborate to regulate protein kinase A activity in Saccharomyces cerevisiae.
abstract: The Sch9 protein kinase regulates Hsp90-dependent signal transduction activity in the budding yeast Saccharomyces cerevisiae. Hsp90 functions in concert with a number of cochaperones, including the Hsp110 homolog Sse1. In this report, we demonstrate a novel synthetic genetic interaction between SSE1 and SCH9. This interaction was observed specifically during growth at elevated temperature and was suppressed by decreased signaling through the protein kinase A (PKA) signal transduction pathway. Correspondingly, sse1Delta sch9Delta cells were shown by both genetic and biochemical approaches to have abnormally high levels of PKA activity and were less sensitive to modulation of PKA by glucose availability. Growth defects of an sse1Delta mutant were corrected by reducing PKA signaling through overexpression of negative regulators or growth on nonoptimal carbon sources. Hyperactivation of the PKA pathway through expression of a constitutive RAS2 allele likewise resulted in temperature-sensitive growth, suggesting that modulation of PKA activity during thermal stress is required for adaptation and viability. Together these results demonstrate that the Sse1 chaperone and the growth control kinase Sch9 independently contribute to regulation of PKA signaling.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas 77030, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Trott
authors.forename: Lance
authors.initials: L
authors.lastname: Shaner
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Morano
mesh_terms: D015152:Blotting, Northern; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D050957:HSP110 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D013696:Temperature
chemical_list: D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C494656:SSE1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C071569:SCH9 protein kinase; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose