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Modulation of human checkpoint kinase Chk1 by the regulatory β-subunit of protein kinase CK2

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Abstract

Protein kinase CK2 is a serine/threonine protein kinase involved in various aspects of cellular regulation. The regulatory β-subunit of CK2 exerts a central role not only in mediating formation of tetrameric CK2 complexes but also as a docking partner for several protein kinases. In this study, CK2β is found to interact with the human cell cycle checkpoint kinase Chk1. The Chk1-interacting region of CK2β is localized at the C-terminus and the complex between CK2β and Chk1 is devoid of the catalytic CK2α-subunit. The interaction between CK2β and Chk1 leads to an increase in the Cdc25C phosphorylation activity of Chk1. The screening of several cell lines has revealed that the association between CK2β and Chk1 also occurs in vivo at a different degree. Collectively, these studies confirm the implication of the regulatory β-subunit of protein kinase CK2 in cell cycle regulation and identify a novel mechanism for the activation of Chk1 protein kinase.

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Acknowledgements

We thank Dr Richard Kolodner for use of SMART Chromatographic System, Dr Karsten Niefind for the release of modeling data and Drs Nelson Chau and Isabella Gazzoli for helpful discussions and suggestions. This work was supported by the Danish Cancer Society (Grant No. DP00035) to BAG and the National Cancer Institute (Grant No. CA43054) to JYJW.

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Authors and Affiliations

  1. Division of Biological Sciences 0322, University of California, San Diego, 92093-0322, CA, USA

    Barbara Guerra & Jean YJ Wang

  2. Institute for Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, Odense, 5230, DK, Denmark

    Barbara Guerra & Olaf-Georg Issinger

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  1. Barbara Guerra
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  2. Olaf-Georg Issinger
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  3. Jean YJ Wang
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Correspondence to Barbara Guerra.

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Guerra, B., Issinger, OG. & Wang, J. Modulation of human checkpoint kinase Chk1 by the regulatory β-subunit of protein kinase CK2. Oncogene 22, 4933–4942 (2003). https://doi.org/10.1038/sj.onc.1206721

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  • DOI: https://doi.org/10.1038/sj.onc.1206721

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