Cdc37 interacts with the glycine-rich loop of Hsp90 client kinases.

Recently, we identified a client-binding site of Cdc37 that is required for its association with protein kinases. Phage display technology and liquid chromatography-tandem mass spectrometry (which identifies a total of 33 proteins) consistently identify a unique sequence, GXFG, as a Cdc37-interacting motif that occurs in the canonical glycine-rich loop (GXGXXG) ...
of protein kinases, regardless of their dependence on Hsp90 or Cdc37. The glycine-rich motif of Raf-1 (GSGSFG) is necessary for its association with Cdc37; nevertheless, the N lobe of Raf-1 (which includes the GSGSFG motif) on its own cannot interact with Cdc37. Chimeric mutants of Cdk2 and Cdk4, which differ sharply in their affinities toward Cdc37, show that their C-terminal portions may determine this difference. In addition, a nonclient kinase, the catalytic subunit of cyclic AMP-dependent protein kinase, interacts with Cdc37 but only when a threonine residue in the activation segment of its C lobe is unphosphorylated. Thus, although a region in the C termini of protein kinases may be crucial for accomplishing and maintaining their interaction with Cdc37, we conclude that the N-terminal glycine-rich loop of protein kinases is essential for physically associating with Cdc37.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Cycle Proteins, Cells, Cultured, Chaperonins, Cyclic AMP-Dependent Protein Kinases, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase 4, Glycine, HSP90 Heat-Shock Proteins, Humans, Molecular Sequence Data, Mutation, Phosphorylation, Protein Interaction Mapping, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-raf, Threonine
Mol. Cell. Biol.
Date: May. 01, 2006
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