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Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation

Oncogene volume 21, pages 7630–7641 (2002)Cite this article

Abstract

The pEg3 protein is a member of the evolutionarily conserved KIN1/PAR-1/MARK kinase family which is involved in cell polarity and microtubule dynamics. In Xenopus, pEg3 has been shown to be a cell cycle dependent kinase whose activity increases to a maximum level during mitosis of the first embryonic cell division. CDC25B is one of the three CDC25 phosphatase genes identified in human. It is thought to regulate the G2/M progression by dephosphorylating and activating the CDK/cyclin complexes. In the present study we show that the human pEg3 kinase is able to specifically phosphorylate CDC25B in vitro. One phosphorylation site was identified and corresponded to serine 323. This residue is equivalent to serine 216 in human CDC25C which plays an important role in the regulation of phosphatase during the cell cycle and at the G2 checkpoint. pEg3 is also able to specifically associate with CDC25B in vitro and in vivo. We show that the ectopic expression of active pEg3 in human U2OS cells induces an accumulation of cells in G2. This effect is counteracted by overexpression of CDC25B. Taken together these results suggest that pEg3 is a potential regulator of the G2/M progression and may act antagonistically to the CDC25B phosphatase.

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Acknowledgements

We are very grateful to the Kazusa Research Institute for providing us with the KIAA0175 cDNA. We also thank Martha Molinari for the kind gift of CDC25A expression plasmid. We are grateful to Dr J-G Delcros and S Lelouch for their help with FACS analysis presented in Figure 7. Support for this work was provided by the Comité de la Haute-Garonne de la Ligue contre le Cancer and by the Association pour la Recherche contre le Cancer (programme ARECA and ARC no: 5960).

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  1. Noélie Davezac and Véronique Baldin: Noélie Davezac and Véronique Baldin contributed equally to this work

Authors and Affiliations

  1. LBCMCP-CNRS UMR5088, IFR109, Université Paul Sabatier, 118 Route de Narbonne, Toulouse cedex, 31062, France

    Noélie Davezac, Véronique Baldin & Bernard Ducommun

  2. UMR6061-CNRS, IFR 97, Université de Rennes 1, 2 avenue du Professeur Léon Bernard, CS34317, Rennes Cedex, 35043, France

    Joëlle Blot & Jean-Pierre Tassan

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  1. Noélie Davezac
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  2. Véronique Baldin
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Correspondence to Jean-Pierre Tassan.

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Davezac, N., Baldin, V., Blot, J. et al. Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation. Oncogene 21, 7630–7641 (2002). https://doi.org/10.1038/sj.onc.1205870

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