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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.

Pubmed ID: 12499358

Authors

  • Lee P
  • Rao J
  • Fliss A
  • Yang E
  • Garrett S
  • Caplan AJ

Journal

The Journal of cell biology

Publication Data

December 23, 2002

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 5T32DK07645
  • Agency: NIDDK NIH HHS, Id: DK60598
  • Agency: NIGMS NIH HHS, Id: GM66644

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