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Multisite phosphorylation of Erk5 in mitosis

Elena Díaz-Rodríguez1, Atanasio Pandiella

  • 1Instituto de BiologIa Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007-Salamanca, Spain.

Journal of Cell Science
|August 26, 2010
PubMed

Insights

A second pathway regulates the MAP kinase Erk5 during mitosis, distinct from the classic MEK5 pathway. This novel pathway, involving CDK1, impacts Erk5

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Mitogen-activated protein (MAP) kinase Erk5 is crucial for cellular proliferation and mitosis.
  • Erk5 is classically activated by dual phosphorylation at its TEY motif via MEK5.
  • The regulation of Erk5 during mitosis remains incompletely understood.

Purpose of the Study:

  • To identify alternative pathways regulating Erk5 phosphorylation during mitosis.
  • To investigate the role of specific kinases in mitotic Erk5 phosphorylation.
  • To elucidate the functional consequences of mitotic Erk5 phosphorylation.

Main Methods:

  • Utilized CDK1 inhibitor RO3306 to assess its effect on Erk5 phosphorylation.
  • Performed co-precipitation assays to examine Erk5 and CDK1 interaction.
  • Analyzed Erk5 phosphorylation sites in the C-terminal region.
  • Investigated Erk5 subcellular localization and transcriptional activity.

Main Results:

  • A novel Erk5 phosphorylation pathway, independent of MEK5, is active in mitotic cells.
  • CDK1 activity is essential for maintaining mitotic Erk5 phosphorylation.
  • CDK1 directly interacts with Erk5 during mitosis.
  • Mitotic phosphorylation occurs at multiple C-terminal sites, influencing Erk5 nuclear transport and transcriptional activity.

Conclusions:

  • Discovered a second, MEK5-independent pathway for Erk5 phosphorylation during mitosis.
  • CDK1 is a key regulator of this novel mitotic Erk5 phosphorylation pathway.
  • Mitotic Erk5 phosphorylation by CDK1 impacts its subcellular localization and function.

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