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Science 330 (6011): 1673-1677

Copyright © 2010 by the American Association for the Advancement of Science

The Substrate of Greatwall Kinase, Arpp19, Controls Mitosis by Inhibiting Protein Phosphatase 2A

Aicha Gharbi-Ayachi,1 Jean-Claude Labbé,1 Andrew Burgess,1 Suzanne Vigneron,1 Jean-Marc Strub,2 Estelle Brioudes,1 Alain Van-Dorsselaer,2 Anna Castro,1,*,{dagger} Thierry Lorca1,*,{dagger}

Abstract: Initiation and maintenance of mitosis require the activation of protein kinase cyclin B–Cdc2 and the inhibition of protein phosphatase 2A (PP2A), which, respectively, phosphorylate and dephosphorylate mitotic substrates. The protein kinase Greatwall (Gwl) is required to maintain mitosis through PP2A inhibition. We describe how Gwl activation results in PP2A inhibition. We identified cyclic adenosine monophosphate–regulated phosphoprotein 19 (Arpp19) and {alpha}-Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. Conversely, in the absence of Gwl activity, Arpp19 and {alpha}-Endosulfine are dephosphorylated and lose their capacity to bind and inhibit PP2A. Although both proteins can inhibit PP2A, endogenous Arpp19, but not {alpha}-Endosulfine, is responsible for PP2A inhibition at mitotic entry in Xenopus egg extracts.

1 Universités Montpellier 2 et 1, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, IFR 122, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
2 Institut Pluridisciplinaire Hubert Curien, Strasbourg Cedex, France.

{dagger} These authors contributed equally to this work.

* To whom correspondence should be addressed. E-mail: anna.castro{at} (A.C.); thierry.lorca{at} (T.L.)

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