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Protein kinase CK2 regulates CDC25B phosphatase activity

Oncogene volume 22, pages 220–232 (2003)Cite this article

Abstract

Human dual-specificity phosphatases CDC25 (A, B and C) play an important role in the control of cell cycle progression by activating the cyclin-dependent kinases (CDKs). Regulation of these phosphatases during the cell cycle involves post-translational modifications such as phosphorylation and protein–protein interactions. Given the suspected involvement of the protein kinase CK2 at the G2/M transition, we have investigated its effects on the CDC25B phosphatase. We show that in vitro CK2 phosphorylates CDC25B, but not CDC25C. Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. We also report that CDC25B interacts with CK2, and this interaction, mediated by the CK2β regulatory subunit, involves domains that are located within the first 55 amino acids of CK2β and between amino acids 122 and 200 on CDC25B. This association was confirmed in vivo, in Sf9 insect cells and in U2OS human cells expressing an HA epitope-tagged CDC25B. Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo. We discuss the possibility that CDC25B phosphorylation by CK2 could play a role in the regulation of the activity of CDC25B as a starter of mitosis.

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Acknowledgements

We thank JM Blanchard, JM Darbon and J Smith for comments on the manuscript and Euralis Génétique for technical assistance. This work was supported by the CNRS, l'Université Paul Sabatier, la Fondation pour la Recherche Médicale (FRM), le pôle ARECA-Protéomique Cancer et la Ligue Nationale contre le Cancer. NT-F was supported by a MENRT fellowship.

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Authors and Affiliations

  1. LBCMCP-CNRS UMR 5088, Institut d'Exploration Fonctionnelle des Génomes-IFR 109, Université Paul Sabatier, 118 Route de Narbonne, Toulouse, 31062, France

    Nathalie Theis-Febvre, Martine Cazales, Bernard Ducommun & Véronique Baldin

  2. INSERM EMI 0104, CEA DBMS, 17, Rue des Martyrs, Grenoble, 38054, cedex, 9, France

    Odile Filhol & Claude Cochet

  3. IPBS, UMR 5089, 205 Route de Narbonne, Toulouse, 31070, France

    Carine Froment & Bernard Monsarrat

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  1. Nathalie Theis-Febvre
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  2. Odile Filhol
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Correspondence to Véronique Baldin.

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Theis-Febvre, N., Filhol, O., Froment, C. et al. Protein kinase CK2 regulates CDC25B phosphatase activity. Oncogene 22, 220–232 (2003). https://doi.org/10.1038/sj.onc.1206107

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