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Aurora-B associated protein phosphatases as negative regulators of kinase activation

Oncogene volume 21, pages 3103–3111 (2002)Cite this article

Abstract

The human serine/threonine kinase Aurora-B is structurally related to the protein kinase Ipl1p from S cerevisiae and aurora from Drosophila melanogaster, which are key regulators of mitosis. The present study shows that human Aurora-B is activated by okadaic acid and forms complexes with the protein serine/threonine phosphatase type 1 (PP1) or PP2A, but not with PP5. These data identified Aurora-B associated protein phosphatases as negative regulators of kinase activation. We then used a series of substrates based on a histone H3 phosphorylation site (residues 5–15) to determine the substrate specificity of human Aurora-B. We found that this enzyme is an arginine-directed kinase that can phosphorylate histone H3 at serines 10 and 28 in vitro, suggesting that human Aurora-B is a mitotic histone H3 kinase.

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Acknowledgements

We thank Dr Tadashi Yamamoto (University of Tokyo, Tokyo) for pME-Gex4T-1 and Ms Tomoko Tsurutome for excellent technical assistance. This work was supported by grants-in-aid for Scientific Research and Core of Excellence from the Ministry of Education, Science, Sports and Culture of Japan.

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Author notes

  1. Keiichi Sugiyama and Kazumitsu Sugiura: K Sugiyama and K Sugiura equally contributed to this work.

Authors and Affiliations

  1. Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya, 466-0065, Japan

    Keiichi Sugiyama, Kazumitsu Sugiura, Tomohiro Hara, Kei Honda, Koichi Furukawa & Takeshi Urano

  2. Department of Nature Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Keiichi Sugiyama & Shunichi Yamashita

  3. Division of Applied Biochemistry, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Sakai, 599-8531, Osaka, Japan

    Kenji Sugimoto

  4. Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-0815, Japan

    Hiroshi Shima

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  1. Keiichi Sugiyama
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Correspondence to Takeshi Urano.

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Sugiyama, K., Sugiura, K., Hara, T. et al. Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene 21, 3103–3111 (2002). https://doi.org/10.1038/sj.onc.1205432

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