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Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways

Oncogene volume 21, pages 6633–6640 (2002)Cite this article

Abstract

The Polo-like kinases (Plks) are a conserved family of kinases that contribute to cell cycle regulation, particularly in G2 and mitosis. In mammals, there are at least three members of the Plk family. Here we show that Plk3 is a stress response protein that becomes phosphorylated following DNA damage or mitotic spindle disruption. Phosphorylation enhances its kinase activity and is dependent upon ataxia telangiectasia-mutated (ATM) in the former case but not the latter. Plk3 associates with complexes of multiple sizes ranging from 150 to greater then 600 kDa. In its unphosphorylated form it elutes from a sizing column at about 400 kDa whereas it associates with complexes of 150 and 600 kDa when phosphorylated. Among the proteins with which it physically associates and utilizes, as substrates are Chk2 and P53. It phosphorylates Chk2 on a residue different from threonine 68 (Thr68), the principal target for ATM. While ATM is necessary for phosphorylation and activation of Chk2 in vivo, Plk3 seems to contribute to its full activation. In its phosphorylated form it also coelutes and forms a complex with unpolymerized tubulin. In aggregate, the data argue that Plk3 is a multifunctional protein that associates with multiple complexes and that contributes to response to stress incurred by DNA damage and mitotic spindle disruption, albeit via different pathways.

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Abbreviations

ATM:

ataxia telangiectasia mutated

CIP:

calf intestinal phosphatase

FPLC:

fast protein liquid chromatography

Plk:

polo-like kinase

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Acknowledgements

This work was supported by the Ruth Lyons Fund and by NIH R01 CA90934, and NIH UO1 ES011038. CW Conn was supported by training grant T32 ES07250.

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Authors and Affiliations

  1. Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, 45267, Ohio, OH, USA

    El Mustapha Bahassi, David L Myer, Robert F Hennigan & Peter J Stambrook

  2. Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 38105, Tennessee, TN, USA

    Christopher W Conn

  3. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, 92037, CA, USA

    Clare H McGowan

  4. Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, 45267, Ohio, OH, USA

    Yolanda Sanchez

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  1. El Mustapha Bahassi
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Correspondence to Peter J Stambrook.

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Bahassi, E., Conn, C., Myer, D. et al. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene 21, 6633–6640 (2002). https://doi.org/10.1038/sj.onc.1205850

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