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Nat Commun. 2014;5:3318. doi: 10.1038/ncomms4318.

Phosphorylation of ARPP19 by protein kinase A prevents meiosis resumption in Xenopus oocytes.

Author information

1
1] Sorbonne Universités, UPMC Univ Paris 06, UMR7622-Biologie du Développement, Paris F-75005, France [2] CNRS, UMR7622-Biologie du Développement, Paris F-75005, France [3].
2
1] Sorbonne Universités, UPMC Univ Paris 06, UMR7622-Biologie du Développement, Paris F-75005, France [2] CNRS, UMR7622-Biologie du Développement, Paris F-75005, France [3] Sorbonne Universités, UPMC Univ Paris 06, IFD, 4 Place Jussieu, cedex 05, Paris 75252, France [4].
3
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
4
1] Sorbonne Universités, UPMC Univ Paris 06, UMR7622-Biologie du Développement, Paris F-75005, France [2] CNRS, UMR7622-Biologie du Développement, Paris F-75005, France.

Abstract

During oogenesis, oocytes are arrested in prophase and resume meiosis by activating the kinase Cdk1 upon hormonal stimulation. In all vertebrates, release from prophase arrest relies on protein kinase A (PKA) downregulation and on the dephosphorylation of a long sought but still unidentified substrate. Here we show that ARPP19 is the PKA substrate whose phosphorylation at serine 109 is necessary and sufficient for maintaining Xenopus oocytes arrested in prophase. By downregulating PKA, progesterone, the meiotic inducer in Xenopus, promotes partial dephosphorylation of ARPP19 that is required for the formation of a threshold level of active Cdk1. Active Cdk1 then initiates the MPF autoamplification loop that occurs independently of both PKA and ARPP19 phosphorylation at serine 109 but requires the Greatwall (Gwl)-dependent phosphorylation of ARPP19 at serine 67. Therefore, ARPP19 stands at a crossroads in the meiotic M-phase control network by integrating differential effects of PKA and Gwl, two kinases essential for meiosis resumption.

PMID:
24525567
PMCID:
PMC4014304
DOI:
10.1038/ncomms4318
[Indexed for MEDLINE]
Free PMC Article

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