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G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A
Journal article   Open access   Peer reviewed

G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A

Brian C. Duckworth, Jennifer S. Weaver, Joan V. Ruderman and Jennifer S Stanford
Proceedings of the National Academy of Sciences - PNAS, v 99(26), pp 16794-16799
11 Dec 2002
DOI: https://doi.org/10.1073/pnas.222661299
PMID: 12477927
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1073/pnas.222661299View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Biological Sciences
Xenopus oocytes, which are arrested in G 2 of meiosis I, contain complexes of cyclin B–cdc2 (M phase-promoting factor) that are kept repressed by inhibitory phosphorylations on cdc2 at Thr-14 and Tyr-15. Progesterone induces a cytoplasmic signaling pathway that leads to activation of cdc25, the phosphatase that removes these phosphorylations, catalyzing entry into M phase. It has been known for 25 years that high levels of cAMP and protein kinase A (PKA) are required to maintain the G 2 arrest and that a drop in PKA activity is required for M phase-promoting factor activation, but no physiological targets of PKA have been identified. We present evidence that cdc25 is a critical target of PKA. ( i ) In vitro , cdc25 Ser-287 serves as a major site of phosphorylation by PKA, resulting in sequestration by 14-3-3. ( ii ) Endogenous cdc25 is phosphorylated on Ser-287 in oocytes and dephosphorylated in response to progesterone just before cdc2 dephosphorylation and M-phase entry. ( iii ) High PKA activity maintains phosphorylation of Ser-287 in vivo , whereas inhibition of PKA by its heat-stable inhibitor (PKI) induces dephosphorylation of Ser-287. ( iv ) Overexpression of mutant cdc25 (S287A) bypasses the ability of PKA to maintain oocytes in G 2 arrest. These findings argue that cdc25 is a physiologically relevant target of PKA in oocytes. In the early embryonic cell cycles, Ser-287 is phosphorylated during interphase and dephosphorylated just before cdc2 activation and mitotic entry. Thus, in addition to its role in checkpoint arrest, cdc25 Ser-287 serves as a site for regulation during normal, unperturbed cell cycles.

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Cell Biology
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