The Cdc37 protein kinase-binding domain is sufficient for protein kinase activity and cell viability.

Cdc37 is a molecular chaperone required for folding of protein kinases. It functions in association with Hsp90, although little is known of its mechanism of action or where it fits into a folding pathway involving other Hsp90 cochaperones. Using a genetic approach with Saccharomyces cerevisiae, we show that CDC37 overexpression ...
suppressed a defect in v-Src folding in yeast deleted for STI1, which recruits Hsp90 to misfolded clients. Expression of CDC37 truncation mutants that were deleted for the Hsp90-binding site stabilized v-Src and led to some folding in both sti1Delta and hsc82Delta strains. The protein kinase-binding domain of Cdc37 was sufficient for yeast cell viability and permitted efficient signaling through the yeast MAP kinase-signaling pathway. We propose a model in which Cdc37 can function independently of Hsp90, although its ability to do so is restricted by its normally low expression levels. This may be a form of regulation by which cells restrict access to Cdc37 until it has passed through a triage involving other chaperones such as Hsp70 and Hsp90.
Mesh Terms:
Binding Sites, Blotting, Western, Cell Cycle Proteins, Drosophila Proteins, Genetic Complementation Test, Glutathione Transferase, HSP70 Heat-Shock Proteins, HSP90 Heat-Shock Proteins, MAP Kinase Signaling System, Models, Biological, Molecular Chaperones, Mutation, Oncogene Protein pp60(v-src), Plasmids, Protein Binding, Protein Folding, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Temperature
J. Cell Biol.
Date: Dec. 23, 2002
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