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Activation-independent nuclear translocation of mitogen activated protein kinase ERK1 mediated by thiol-modifying

R Meili1, K Ballmer-Hofer

  • 1Friedrich Miescher Institute, Basel, Switzerland.

FEBS Letters
|September 23, 1996
PubMed

Insights

Extracellular signal-regulated kinases (ERK1/2) mediate cell growth signals. Thiol-modifying chemicals induce ERK1 nuclear translocation without activation, suggesting a cytoplasmic retention mechanism.

Area of Science:

  • Cellular biology
  • Molecular signaling pathways

Background:

  • Extracellular signal-regulated kinases (ERK1 and ERK2) are crucial for transmitting mitogenic signals.
  • Sustained ERK1/2 activation and nuclear entry are essential for fibroblast S-phase progression.
  • Mechanisms governing ERK1/2 nuclear translocation remain largely unelucidated.

Purpose of the Study:

  • To investigate the translocation mechanism of ERK1, independent of its activation status.
  • To identify factors involved in regulating ERK1 cytoplasmic localization.

Main Methods:

  • Indirect immunofluorescence microscopy to visualize ERK1 localization.
  • Biochemical assays to assess protein activation and modification.
  • Treatment of fibroblasts with thiol-modifying chemicals.

Main Results:

  • ERK1 demonstrated nuclear translocation in response to thiol-modifying chemicals, irrespective of activation or phosphorylation.
  • These chemicals appear to disrupt a protein responsible for retaining ERK1 in the cytoplasm.

Conclusions:

  • Nuclear translocation of ERK1 can occur independently of upstream activation signals.
  • A cytoplasmic retention mechanism for ERK1, potentially involving thiol-dependent interactions, is proposed.

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