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Nat Commun 2021 Jun 11;121:3565. doi: 10.1038/s41467-021-23657-0.
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The study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop.

Labbé JC , Vigneron S , Méchali F , Robert P , Roque S , Genoud C , Goguet-Rubio P , Barthe P , Labesse G , Cohen-Gonsaud M , Castro A , Lorca T .

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.

PubMed ID: 34117214
PMC ID: PMC8196004
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: arpp19 camk2g cdk1 ensa mastl mbp mink1 prc1 ptpa
GO keywords: phosphorylation [+]

Article Images: [+] show captions
References [+] :
Abrieu, MAPK inactivation is required for the G2 to M-phase transition of the first mitotic cell cycle. 1998, Pubmed, Xenbase