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

K Terasawa, K Yoshimatsu, S Iemura… - … and cellular biology, 2006 - Taylor & Francis
K Terasawa, K Yoshimatsu, S Iemura, T Natsume, K Tanaka, Y Minami
Molecular and cellular biology, 2006Taylor & Francis
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 …
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.
Taylor & Francis Online