Cdc37 promotes the stability of protein kinases Cdc28 and Cak1.
In the budding yeast Saccharomyces cerevisiae, Cdc37 is required for the productive formation of Cdc28-cyclin complexes. The cdc37-1 mutant arrests at Start with low levels of Cdc28 protein, which is predominantly unphosphorylated at Thr169, fails to bind cyclin, and has little protein kinase activity. We show here that Cdc28 and not cyclin is specifically defective in the cdc37-1 mutant and that Cdc37 likely does not act as an assembly factor for Cdc28-cyclin complex formation. We have also found that the levels and activity of the protein kinase Cak1 are significantly reduced in the cdc37-1 mutant. Pulse-chase analysis indicates that Cdc28 and Cak1 proteins are both destabilized when Cdc37 function is absent during but not after translation. In addition, Cdc37 promotes the production of Cak1, but not that of Cdc28, when coexpressed in insect cells. We conclude that budding yeast Cdc37, like its higher eukaryotic homologs, promotes the physical integrity of multiple protein kinases, perhaps by virtue of a cotranslational role in protein folding.
Farrell
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Department of Physiology, University of California, San Francisco, California 94143-0444, USA.
Morgan
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D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases; D029721:Drosophila Proteins; D004795:Enzyme Stability; D005838:Genotype; D007700:Kinetics; D018832:Molecular Chaperones; D016296:Mutagenesis; D010766:Phosphorylation; D010769:Phosphothreonine; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D000095043:Cyclin-Dependent Kinase-Activating Kinase
C513270:CDC37 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D010769:Phosphothreonine; D017346:Protein Serine-Threonine Kinases; D017489:CDC28 Protein Kinase, S cerevisiae; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase