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

Abstract : 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.
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https://hal-cnrs.archives-ouvertes.fr/hal-03263787
Contributor : Thierry Lorca Connect in order to contact the contributor
Submitted on : Wednesday, June 23, 2021 - 7:38:48 AM
Last modification on : Friday, October 22, 2021 - 2:28:07 PM
Long-term archiving on: : Friday, September 24, 2021 - 6:09:08 PM

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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, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-23657-0⟩. ⟨hal-03263787⟩

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