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Roles of Greatwall kinase in the regulation of cdc25 phosphatase

Yong Zhao1, Olivier Haccard, Ruoning Wang

  • 1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USA.

Molecular Biology of the Cell
|January 18, 2008
PubMed

Insights

Greatwall kinase is crucial for cell cycle progression, regulating M phase entry by controlling Cdc25 activation. It acts by inhibiting a phosphatase that normally blocks this process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Greatwall kinase is involved in regulating M phase entry in Xenopus egg extracts.
  • It is part of an autoregulatory loop with M phase-promoting factor (MPF).
  • Inhibitory phosphorylations on Cdc2 are linked to M phase prevention when Greatwall is depleted.

Purpose of the Study:

  • To investigate the role of activated Greatwall kinase in regulating the G2/M transition and meiotic maturation.
  • To elucidate the mechanism by which Greatwall kinase influences Cdc25 activation and M phase induction.

Main Methods:

  • Immunodepletion of Greatwall kinase in Xenopus egg extracts.
  • Activation of Greatwall kinase in cycling egg extracts and G2-arrested oocytes.
  • Analysis of Cdc25 phosphorylation in the presence/absence of various kinases and inhibitors.
  • Treatment with okadaic acid (OA), a phosphatase inhibitor.

Main Results:

  • Activated Greatwall kinase accelerates the G2/M transition and induces meiotic maturation independently of progesterone.
  • Greatwall kinase induces Cdc25 phosphorylation even without active Cdc2, Plx1, or MAPK, and overrides protein kinase A-mediated mitotic block.
  • The effects of activated Greatwall mimic those of okadaic acid.
  • Okadaic acid enables M phase entry in the absence of Greatwall.

Conclusions:

  • Greatwall kinase plays a critical role in promoting M phase entry.
  • Greatwall kinase negatively regulates a phosphatase that inhibits Cdc25 activation.
  • This mechanism is essential for timely M phase induction and meiotic maturation.

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