Journal of Biological Chemistry
Volume 278, Issue 40, 3 October 2003, Pages 38117-38120
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Phosphorylation of Serine 13 Is Required for the Proper Function of the Hsp90 Co-chaperone, Cdc37*

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The Hsp90 co-chaperone Cdc37 provides an essential function for the biogenesis and support of numerous protein kinases. In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site. Mutation of Ser13 to either Ala or Glu compromises the recruitment of Cdc37 to Hsp90-kinase complexes but has only modest effects on its basal (client-free) binding to Hsp90. Furthermore, Cdc37 containing the complementing Ser to Glu mutation showed altered interactions with Hsp90-kinase complexes consistent with compromised Cdc37 modulation of the Hsp90 ATP-driven reaction cycle. Thus, the data indicate that phosphorylation of Cdc37 on Ser13 is critical for its ability to coordinate Hsp90 nucleotide-mediated conformational switching and kinase binding.

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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. This work was supported by the American Heart Association (Grant 0250556N to R. L. M.) and by the Oklahoma Agricultural Experiment Station (Project 1975).