The M phase kinase Greatwall (Gwl) promotes inactivation of PP2A/B55delta, a phosphatase directed against CDK

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Priscila V Castilho1, Byron C Williams, Satoru Mochida

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

Molecular Biology of the Cell
|October 2, 2009
PubMed

Insights

Greatwall kinase (Gwl) inactivates specific phosphatases during M phase, enabling cell cycle progression. This Gwl-dependent mechanism is crucial for maintaining M phase by preventing the removal of cyclin-dependent kinase (CDK) phosphorylations.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Greatwall kinase (Gwl) is essential for M phase entry and maintenance in Xenopus egg extracts.
  • Cyclin-dependent kinases (CDKs) drive M phase through phosphorylation events.

Purpose of the Study:

  • To elucidate the role of Gwl in a novel biochemical pathway during M phase.
  • To investigate how Gwl interacts with phosphatases that oppose CDK activity.

Main Methods:

  • Utilized Xenopus egg extracts to study M phase regulation.
  • Investigated the biochemical activity of Gwl and its interaction with PP2A/B55delta.
  • Assessed the impact of Gwl depletion on M phase entry and phosphatase activity.

Main Results:

  • Gwl is activated by Cdk1/cyclin B (MPF) during M phase.
  • Activated Gwl inhibits the activity of heterotrimeric PP2A containing the B55delta regulatory subunit, an "antimitotic" phosphatase.
  • Gwl-mediated inhibition of PP2A/B55delta is independent of MPF once Gwl is activated.
  • In the absence of Gwl, PP2A/B55delta remains active, preventing M phase entry.
  • Depletion of PP2A/B55delta rescues M phase entry in Gwl-depleted extracts.

Conclusions:

  • M phase entry and maintenance require both high MPF activity and the suppression of specific phosphatases.
  • Gwl acts through a novel pathway to inhibit "antimitotic" phosphatases like PP2A/B55delta.
  • This Gwl-dependent suppression of phosphatase activity is critical for overcoming the inhibitory effects of these phosphatases on MPF-driven phosphorylations, thereby ensuring proper M phase progression.

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