Non-regulated and stimulated mechanisms cooperate in the nuclear accumulation of MEK1

Oncogene. 2001 Nov 15;20(52):7588-96. doi: 10.1038/sj.onc.1204963.


MEKs, which operate within the ERK cascade, shuttle into the nucleus, but are rapidly exported from this location, forming an apparent cytosolic distribution both before and after stimulation. Two different mechanisms have been proposed for the nuclear translocation of MEKs. One of them involves a constant and non-regulated shuttling of MEKs into the nucleus operating both before and after mitogenic stimulation. The other mechanism seems to require the activity of MEKs and is facilitated in response to mitogenic stimulation. Here we show that these two mechanisms may coexist in the same cells. We found that leptomycin B (LMB), a potent inhibitor of nuclear export, induces a nuclear accumulation of MEKs, and this was significantly facilitated by stimulation of LMB-treated cells with EGF, TPA and peroxovanadate. The EGF-stimulated, but not the LMB-induced translocation was attenuated by MEK inhibitors and by using inactive forms of MEK1. We also show that LMB slightly activates the ERK cascade, but this activity only partially induces the nuclear accumulation of MEKs in cells treated by LMB alone. Thus, MEKs translocate into the nucleus by a combination of non-regulated and stimulated processes that contribute to the nuclear translocation of MEKs either in resting cells or upon mitogenic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • COS Cells
  • Cell Line
  • Cell Nucleus / metabolism*
  • Chlorocebus aethiops
  • Epidermal Growth Factor / pharmacology
  • Fatty Acids, Unsaturated / pharmacology
  • Genes, Reporter
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats


  • Antibiotics, Antineoplastic
  • Fatty Acids, Unsaturated
  • Luminescent Proteins
  • Green Fluorescent Proteins
  • Epidermal Growth Factor
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • leptomycin B