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Phosphatase 2A and polo kinase, two antagonistic regulators of cdc25 activation and MPF auto-amplification

A Karaïskou1, C Jessus, T Brassac

  • 1Laboratoire de Physiologie de la Reproduction, ESA 7080-CNRS, INRA, Université Pierre et Marie Curie, Boîte 13, 75252 Paris cédex 05, France.

Journal of Cell Science
|October 19, 1999
PubMed

Insights

The cyclin-dependent kinase Cdc2/MPF activation involves a two-step feedback loop in Xenopus oocytes. This process requires specific kinase activities and protein interactions for full MPF amplification and M-phase entry.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Cyclin-dependent kinase (Cdc2) or M-phase promoting factor (MPF) auto-catalytic activation drives entry into M phase.
  • A positive feedback loop between Cdc2 kinase and Cdc25 phosphatase enables abrupt MPF activation in Xenopus oocytes.

Purpose of the Study:

  • Investigate the molecular mechanisms of the Cdc2/Cdc25 feedback loop in MPF amplification.
  • Elucidate the two-step model of MPF amplification using cell-free Xenopus oocyte systems.

Main Methods:

  • Utilized cell-free systems derived from Xenopus prophase-arrested oocytes.
  • Analyzed the roles of Cdc2, Cdc25, Plx1, Plkk1, PP2A, and Suc1/Cks in the feedback loop.
  • Investigated protein phosphorylation and complex formation.

Main Results:

  • A two-step model for MPF amplification was proposed.
  • Step 1: Basal Cdc25 activity leads to linear Cdc2 activation and partial Cdc25 phosphorylation, activating Plx1/Plkk1 independently of PP2A or Suc1/Cks.
  • Step 2: Full Cdc25 activation and MPF amplification depend on PP2A inhibition and Plx1 activity, requiring Suc1-dependent Cdc25/Cdc2 interaction.

Conclusions:

  • MPF amplification is a regulated two-step process.
  • Specific molecular players and interactions are critical for each step of MPF activation.
  • The findings provide a detailed mechanistic understanding of meiotic entry regulation.

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