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Originally published In Press as doi:10.1074/jbc.C200307200 on June 4, 2002

J. Biol. Chem., Vol. 277, Issue 31, 27577-27580, August 2, 2002
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ACCELERATED PUBLICATION
Phosphorylation of the Carboxyl Terminus of Inner Centromere Protein (INCENP) by the Aurora B Kinase Stimulates Aurora B Kinase Activity*

John D. BishopDagger § and Jill M. SchumacherDagger ||

From the Dagger  Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030 and the  Genes and Development Program, Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas 77030

How the events of mitosis are coordinated is not well understood. Intriguing mitotic regulators include the chromosomal passenger proteins. Loss of either of the passengers inner centromere protein (INCENP) or the Aurora B kinase results in chromosome segregation defects and failures in cytokinesis. Furthermore, INCENP and Aurora B have identical localization patterns during mitosis and directly bind each other in vitro. These results led to the hypothesis that INCENP is a direct substrate of Aurora B. Here we show that the Caenorhabditis elegans Aurora B kinase AIR-2 specifically phosphorylated the C. elegans INCENP ICP-1 at two adjacent serines within the carboxyl terminus. Furthermore, the full length and a carboxyl-terminal fragment of ICP-1 stimulated AIR-2 kinase activity. This increase in AIR-2 activity required that AIR-2 phosphorylate ICP-1 because mutation of both serines in the AIR-2 phosphorylation site of ICP-1 abolished the potentiation of AIR-2 kinase activity by ICP-1. Thus, ICP-1 is directly phosphorylated by AIR-2 and functions in a positive feedback loop that regulates AIR-2 kinase activity. Since the Aurora B phosphorylation site within INCENP and the functions of INCENP and Aurora B have been conserved among eukaryotes, the feedback loop we have identified is also likely to be evolutionarily conserved.

* This work was supported by National Institutes of Health Grant R01 GM62181-01 and a V-Foundation scholar award (to J. M. S.). All sequencing was performed at The University of Texas M. D. Anderson DNA Sequencing Core funded by NCI, National Institutes of Health Grant CA-16672.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by the Molecular Genetics of Cancer Training Program Grant T32 CA09299.

|| To whom correspondence should be addressed. Tel.: 713-792-8934; Fax: 713-794-4394; E-mail: jschumac@mdanderson.org.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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