%0 Journal Article %T The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop %+ Centre de recherche en Biologie cellulaire de Montpellier (CRBM) %+ Centre de Biochimie Structurale [Montpellier] (CBS) %A Labbé, Jean Claude %A Vigneron, Suzanne %A Méchali, Francisca %A Robert, Perle %A Roque, Sylvain %A Genoud, Cindy %A Goguet-Rubio, Perrine %A Barthe, Phillipe %A Labesse, Gilles %A Cohen-Gonsaud, Martin %A Castro, Anna %A Lorca, Thierry %< avec comité de lecture %@ 2041-1723 %J Nature Communications %I Nature Publishing Group %V 12 %N 1 %8 2021-06-11 %D 2021 %R 10.1038/s41467-021-23657-0 %Z Life Sciences [q-bio]Journal articles %X 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. %G English %2 https://cnrs.hal.science/hal-03263787/document %2 https://cnrs.hal.science/hal-03263787/file/2021TLorca_The%20study%20of%20the%20determinants.pdf %L hal-03263787 %U https://cnrs.hal.science/hal-03263787 %~ INSERM %~ CNRS %~ CRBM %~ CBS %~ BS %~ UNIV-MONTPELLIER %~ TEST-HALCNRS %~ UM-2015-2021