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Mechanism of mitosis-specific activation of MEK1

Angus Harding1, Nichole Giles, Andrew Burgess

  • 1Cancer Biology Program, Centre for Immunology and Cancer Research, University of Queensland, Queensland 4102, Australia.

The Journal of Biological Chemistry
|March 1, 2003
PubMed

Insights

Cyclin B-Cdc2 activity regulates the Mitogen-Activated Protein Kinase (MAPK) pathway during mammalian mitosis. This regulation involves MEK1 cleavage and phosphorylation, uncoupling MEK1 activation from its substrate ERK.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Cyclin B-Cdc2 is essential for mitotic entry.
  • Mitogen-Activated Protein Kinase (MAPK) cascade has roles in mitosis, but its regulation in mammalian cells is unclear.

Purpose of the Study:

  • To analyze the Ras/Raf/MEK/ERK pathway activity in HeLa cells during G(2)/M phase.
  • To investigate the regulation of MAPK signaling by cyclin B-Cdc2 during mitosis.

Main Methods:

  • Analysis of Ras/Raf/MEK/ERK pathway components' activity in HeLa cells.
  • Investigating MEK1 activation and its substrate ERK activation.
  • Studying the mechanism of MEK1 and ERK uncoupling.

Main Results:

  • MEK1 activation occurred without corresponding ERK activation in HeLa cells during G(2)/M.
  • MEK1 activation was uncoupled from ERK activation due to proteolytic cleavage and phosphorylation.
  • Cyclin B-Cdc2 dependent cleavage of MEK1's N-terminal domain and phosphorylation of Thr(286) were identified.

Conclusions:

  • Cyclin B-Cdc2 activity directly regulates MAPK pathway signaling during mitosis.
  • The study reveals a novel mechanism of MAPK pathway regulation in mammalian mitosis.

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