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Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene

A Brunet1, D Roux, P Lenormand

  • 1CNRS-UMR 6543 Centre de Biochimie, Université de Nice, Parc Valrose, 06108 Nice, France.

The EMBO Journal
|February 2, 1999
PubMed

Insights

Mitogen-activated protein kinase (MAPK) nuclear translocation is crucial for gene expression and cell cycle re-entry. Preventing MAPK from entering the nucleus blocks growth factor-induced DNA replication and transcription.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Signal transduction pathways

Background:

  • Mitogen-activated protein kinase (MAPK) modules are key in signal transduction.
  • Mitogenic stimulation causes p42/p44MAPK to move from the cytoplasm to the nucleus in mammalian cells.
  • MAPK's nuclear translocation is proposed as a critical signaling step but lacks direct evidence.

Purpose of the Study:

  • To investigate the role of p42/p44MAPK nuclear translocation in signal transduction.
  • To determine if MAPK nuclear localization is essential for gene transcription and DNA replication.

Main Methods:

  • Utilized a catalytically inactive form of cytoplasmic MAP kinase phosphatase (MKP-3/Pyst-1) to sequester p42/p44MAPK in the cytoplasm.
  • Assessed MAPK activation and phosphorylation of cytoplasmic substrates (p90RSK1, cytoplasmic Elk1).
  • Measured Elk1-dependent gene transcription and DNA replication initiation upon growth factor stimulation.

Main Results:

  • Cytoplasmic sequestration of MAPK did not affect its activation or cytoplasmic substrate phosphorylation.
  • Inhibition of MAPK nuclear translocation significantly reduced Elk1-dependent gene transcription.
  • Preventing MAPK nuclear entry impaired the cells' ability to reinitiate DNA replication.

Conclusions:

  • The nuclear relocalization of MAPK is a critical regulatory step for mitogen-induced gene expression.
  • MAPK's translocation to the nucleus is essential for growth factor-stimulated cell cycle re-entry and DNA replication.

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