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PMID: 15082798 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37.

Molecular and cellular biology ·Vol. 24 ·No. 9 ·2004-05-00 ·Pages 4065-74

Miyata Y, Nishida E

Abstract

Cdc37 is a kinase-associated molecular chaperone whose function in concert with Hsp90 is essential for many signaling protein kinases. Here, we report that mammalian Cdc37 is a pivotal substrate of CK2 (casein kinase II). Purified Cdc37 was phosphorylated in vitro on a conserved serine residue, Ser13, by CK2. Moreover, Ser13 was the unique phosphorylation site of Cdc37 in vivo. Crucially, the CK2 phosphorylation of Cdc37 on Ser13 was essential for the optimal binding activity of Cdc37 toward various kinases examined, including Raf1, Akt, Aurora-B, Cdk4, Src, MOK, MAK, and MRK. In addition, nonphosphorylatable mutants of Cdc37 significantly suppressed the association of Hsp90 with protein kinases, while the Hsp90-binding activity of the mutants was unchanged. The treatment of cells with a specific CK2 inhibitor suppressed the phosphorylation of Cdc37 in vivo and reduced the levels of Cdc37 target kinases. These results unveil a regulatory mechanism of Cdc37, identify a novel molecular link between CK2 and many crucial protein kinases via Cdc37, and reveal the molecular basis for the ability of CK2 to regulate pleiotropic cellular functions.

MeSH Terms
Amino Acid Sequence Animals Carrier Proteins Casein Kinase II Cell Cycle Proteins/genetics,metabolism Chaperonins Drosophila Proteins/genetics,metabolism Humans Male Molecular Chaperones/genetics,metabolism Molecular Sequence Data Mutagenesis, Site-Directed Phosphorylation Protein Kinases/metabolism Protein Serine-Threonine Kinases/metabolism Rats Sequence Alignment Serine/metabolism Signal Transduction/physiology Swine
Chemicals
CDC37 protein, human Carrier Proteins Cdc37 protein, rat Cell Cycle Proteins Drosophila Proteins Molecular Chaperones Serine Protein Kinases Casein Kinase II Protein Serine-Threonine Kinases Chaperonins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Miyata Yoshihiko
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan. [email protected]
Nishida Eisuke
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.9.4065-4074.2004
Email
[email protected]
Published
2004-05-00
Pages
4065-74
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC387775
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.9.4065-4074.2004 PMC Full Text View journal details
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