title: The phosphorylation of ARPP19 by Greatwall renders the auto-amplification of MPF independently of PKA in Xenopus oocytes.
abstract: Entry into mitosis or meiosis relies on the coordinated action of kinases and phosphatases that ultimately leads to the activation of Cyclin-B-Cdk1, also known as MPF for M-phase promoting factor. Vertebrate oocytes are blocked in prophase of the first meiotic division, an arrest that is tightly controlled by high PKA activity. Re-entry into meiosis depends on activation of Cdk1, which obeys a two-step mechanism: a catalytic amount of Cdk1 is generated in a PKA and protein-synthesis-dependent manner; then a regulatory network known as the MPF auto-amplification loop is initiated. This second step is independent of PKA and protein synthesis. However, none of the molecular components of the auto-amplification loop identified so far act independently of PKA. Therefore, the protein rendering this process independent of PKA in oocytes remains unknown. Using a physiologically intact cell system, the Xenopus oocyte, we show that the phosphorylation of ARPP19 at S67 by the Greatwall kinase promotes its binding to the PP2A-B55δ phosphatase, thus inhibiting its activity. This process is controlled by Cdk1 and has an essential role within the Cdk1 auto-amplification loop for entry into the first meiotic division. Moreover, once phosphorylated by Greatwall, ARPP19 escapes the negative regulation exerted by PKA. It also promotes activation of MPF independently of protein synthesis, provided that a small amount of Mos is present. Taken together, these findings reveal that PP2A-B55δ, Greatwall and ARPP19 are not only required for entry into meiotic divisions, but are also pivotal effectors within the Cdk1 auto-regulatory loop responsible for its independence with respect to the PKA-negative control.
authors.affiliation: UPMC Université Paris 06, UMR7622-Biologie du Développement, 9 quai Saint Bernard, 75005, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Dupré
authors.forename: Eulalie
authors.initials: E
authors.lastname: Buffin
authors.forename: Chloé
authors.initials: C
authors.lastname: Roustan
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Catherine
authors.initials: C
authors.lastname: Jessus
authors.forename: Olivier
authors.initials: O
authors.lastname: Haccard
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D016200:Maturation-Promoting Factor / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology; D009865:Oocytes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D019926:Cyclin B; D010750:Phosphoproteins; D029867:Xenopus Proteins; C064321:cyclic AMP-regulated phosphoprotein 19; C544010:MASTL protein, Xenopus; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor; D054648:Protein Phosphatase 2; C584831:ppp2r2a protein, Xenopus laevis
keywords: ARPP19; Cdk1; Greatwall; Meiotic division; PKA; PP2A