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

Oncogene volume 20, pages 7588–7596 (2001)Cite this article

Abstract

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.

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Abbreviations

DP-ERK Ab:

anti diphospho-ERK antibody

ERK:

extracellular signal-regulated kinase

GFP:

green fluorescence protein

LMB:

leptomycin B

MAPK:

mitogen-activated protein kinase

MBP:

myelin basic protein

MEK:

MAPK/ERK kinase

TPA:

tetradecanoyl phorbol acetate

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Acknowledgements

We would like to thank Mrs Tami Hanoch for her technical help. This work was supported by grants from the Benozyio Institute for Molecular Medicine at the Weizmann Institute of Science, the Moross Institute for Cancer Research at the Weizmann Institute of Science, the Estate of Siegmund Landau, and the Israel Academy of Sciences and Humanities.

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Authors and Affiliations

  1. Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel

    Zhong Yao, Inbal Flash, Ziv Raviv, Yuval Yung & Rony Seger

  2. Sigma–Aldrich Israel Ltd., Jerusalem, Israel

    Yael Asscher & Shlomo Pleban

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  1. Zhong Yao
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  2. Inbal Flash
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Correspondence to Rony Seger.

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Yao, Z., Flash, I., Raviv, Z. et al. Non-regulated and stimulated mechanisms cooperate in the nuclear accumulation of MEK1. Oncogene 20, 7588–7596 (2001). https://doi.org/10.1038/sj.onc.1204963

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