title: The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A.
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 α-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 α-Endosulfine are dephosphorylated and lose their capacity to bind and inhibit PP2A. Although both proteins can inhibit PP2A, endogenous Arpp19, but not α-Endosulfine, is responsible for PP2A inhibition at mitotic entry in Xenopus egg extracts.
authors.affiliation: 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.
authors.forename: Aicha
authors.initials: A
authors.lastname: Gharbi-Ayachi
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Labbé
authors.forename: Andrew
authors.initials: A
authors.lastname: Burgess
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vigneron
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Strub
authors.forename: Estelle
authors.initials: E
authors.lastname: Brioudes
authors.forename: Alain
authors.initials: A
authors.lastname: Van-Dorsselaer
authors.forename: Anna
authors.initials: A
authors.lastname: Castro
authors.forename: Thierry
authors.initials: T
authors.lastname: Lorca
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007399:Interphase; D008938:Mitosis; D008969:Molecular Sequence Data; D009865:Oocytes; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; C064321:cyclic AMP-regulated phosphoprotein 19; C075663:endosulfine; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D054648:Protein Phosphatase 2