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

Paul Lee, Jie Rao, Albert Fliss, Emy Yang, Stephen Garrett, Avrom J. Caplan

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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 sti1Δ and hsc82Δ 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.

Original languageEnglish
Pages (from-to)1051-1059
Number of pages9
JournalJournal of Cell Biology
Volume159
Issue number6
DOIs
StatePublished - 23 Dec 2002

Keywords

  • Cdc37
  • Chaperone
  • Hsp90
  • Yeast
  • v-Src

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