The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop - Université de Montpellier
Article Dans Une Revue Nature Communications Année : 2021

The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop

Jean Claude Labbé
  • Fonction : Auteur
Suzanne Vigneron
  • Fonction : Auteur
Francisca Méchali
  • Fonction : Auteur
Perle Robert
  • Fonction : Auteur
Sylvain Roque
  • Fonction : Auteur
Cindy Genoud
  • Fonction : Auteur
Perrine Goguet-Rubio
  • Fonction : Auteur
Gilles Labesse
Martin Cohen-Gonsaud
  • Fonction : Auteur
Thierry Lorca

Résumé

Abstract Arpp19 is a potent PP2A-B55 inhibitor that regulates this phosphatase to ensure the stable phosphorylation of mitotic/meiotic substrates. At G2-M, Arpp19 is phosphorylated by the Greatwall kinase on S67. This phosphorylated Arpp19 form displays a high affinity to PP2A-B55 and a slow dephosphorylation rate, acting as a competitor of PP2A-B55 substrates. The molecular determinants conferring slow dephosphorylation kinetics to S67 are unknown. PKA also phosphorylates Arpp19. This phosphorylation performed on S109 is essential to maintain prophase I-arrest in Xenopus oocytes although the underlying signalling mechanism is elusive. Here, we characterize the molecular determinants conferring high affinity and slow dephosphorylation to S67 and controlling PP2A-B55 inhibitory activity of Arpp19. Moreover, we show that phospho-S109 restricts S67 phosphorylation by increasing its catalysis by PP2A-B55. Finally, we discover a double feed-back loop between these two phospho-sites essential to coordinate the temporal pattern of Arpp19-dependent PP2A-B55 inhibition and Cyclin B/Cdk1 activation during cell division.

Dates et versions

hal-04708404 , version 1 (24-09-2024)

Identifiants

Citer

Jean Claude Labbé, Suzanne Vigneron, Francisca Méchali, Perle Robert, Sylvain Roque, et al.. The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop. Nature Communications, 2021, 12 (1), pp.3565. ⟨10.1038/s41467-021-23657-0⟩. ⟨hal-04708404⟩
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