Hsp90-Dependent Activation of Protein Kinases Is Regulated by Chaperone-Targeted Dephosphorylation of Cdc37
2008

How Cdc37 Phosphorylation Affects Protein Kinase Activation

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Author Information

Author(s): Vaughan Cara K., Mollapour Mehdi, Smith Jennifer R., Truman Andrew, Hu Bin, Good Valerie M., Panaretou Barry, Neckers Len, Clarke Paul A., Workman Paul, Piper Peter W., Prodromou Chrisostomos, Pearl Laurence H.

Primary Institution: Institute of Cancer Research

Hypothesis

The study investigates how the phosphorylation of Cdc37 at Ser13 regulates its function in activating protein kinases through Hsp90 complexes.

Conclusion

Cdc37 phosphorylation is essential for its role in activating protein kinases, and this process is regulated by the phosphatase PP5.

Supporting Evidence

  • Cdc37 requires phosphorylation at Ser13 for its function.
  • PP5 specifically dephosphorylates Cdc37 in Hsp90 complexes.
  • Phosphorylation and dephosphorylation of Cdc37 regulate its activity in kinase activation.
  • Mutations that prevent phosphorylation of Cdc37 impair its function.
  • PP5 overexpression reduces Cdc37 phosphorylation in human cells.

Takeaway

Cdc37 helps activate proteins, and it needs to be 'tagged' with a special marker (phosphorylation) to do its job. Another helper, PP5, can remove this tag when it's not needed.

Methodology

The study used a baculovirus system to express Cdc37 and analyzed its phosphorylation state in various complexes using phosphospecific antibodies.

Digital Object Identifier (DOI)

10.1016/j.molcel.2008.07.021

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