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The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation

Oncogene volume 19, pages 4906–4916 (2000)Cite this article

Abstract

Aurora2 is a cell cycle regulated serine/threonine protein kinase which is overexpressed in many tumor cell lines. We demonstrate that Aurora2 is regulated by phosphorylation in a cell cycle dependent manner. This phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro. The protein phosphatase 1 is shown to dephosphorylate this site in vitro, and in vivo the phosphorylation of T288 is induced by okadaic acid treatment. Furthermore, we show that the Aurora2 kinase is regulated by proteasome dependent degradation and that Aurora2 phosphorylated on T288 may be targeted for degradation during mitosis. Our experiments suggest that phosphorylation of T288 is important for regulation of the Aurora2 kinase both for its activity and its stability.

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Acknowledgements

We thank Fernando Bazan and Vincent Madison for protein sequence analyses and Deepa Prabhavalkar for the recombinant ERK2 enzyme. We also thank Ronald Herbst and the members of the Cell Signalling Department for suggestions and critical review of the manuscript and Gary Burget and Maribel Andonian for assistance with graphics. The DNAX Research Institute is funded by the Schering-Plough Corporation.

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  1. DNAX Research Institute, 901 California Avenue, Palo Alto, 94304, California, CA, USA

    Annette O Walter, Wolfgang Seghezzi, Wouter Korver, Julie Sheung & Emma Lees

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  1. Annette O Walter
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Walter, A., Seghezzi, W., Korver, W. et al. The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation. Oncogene 19, 4906–4916 (2000). https://doi.org/10.1038/sj.onc.1203847

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