In response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK), which localizes to the cytoplasm in quiescent cells, translocates to the nucleus and then relocalizes to the cytoplasm again. The relocalization of nuclear MAPK to the cytoplasm was not inhibited by cycloheximide, confirming that the relocalization is achieved by nuclear export, but not synthesis, of MAPK. The nuclear export of MAPK was inhibited by leptomycin B (LMB), a specific inhibitor of the nuclear export signal (NES)-dependent transport. We have then shown that MAP kinase kinase (MAPKK, also known as MEK), which mostly localizes to the cytoplasm because of its having NES, is able to shuttle between the cytoplasm and the nucleus constantly. MAPK, when injected into the nucleus, was rapidly exported from the nucleus by coinjected wild-type MAPKK, but not by the NES-disrupted MAPKK. In addition, injection of the fragment corresponding to the MAPK-binding site of MAPKK into the nucleus, which would disrupt the binding of MAPK to MAPKK in the nucleus, significantly inhibited the nuclear export of endogenous MAPK. Taken together, these results suggest that the relocalization of nuclear MAPK to the cytoplasm involves a MAPKK-dependent, active transport mechanism.
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6 March 2000
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March 06 2000
Nuclear Export of Map Kinase (ERK) Involves a Map Kinase Kinase (Mek-Dependent) Active Transport Mechanism
Makoto Adachi,
Makoto Adachi
aDepartment of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
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Makoto Fukuda,
Makoto Fukuda
aDepartment of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
bDepartment of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
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Eisuke Nishida
Eisuke Nishida
aDepartment of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
bDepartment of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Search for other works by this author on:
Makoto Adachi
aDepartment of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Makoto Fukuda
aDepartment of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
bDepartment of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Eisuke Nishida
aDepartment of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
bDepartment of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
Abbreviations used in this paper: CHX, cycloheximide; DAPI, 4′,6-diamidino-2-phenylindole; LMB, leptomycin B; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; NES, nuclear export signal; TPA, 12-O-tetra decanoyl phorbol myristate acetate.
Received:
September 30 1999
Revision Requested:
January 27 2000
Accepted:
January 27 2000
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Cell Biol (2000) 148 (5): 849–856.
Article history
Received:
September 30 1999
Revision Requested:
January 27 2000
Accepted:
January 27 2000
Citation
Makoto Adachi, Makoto Fukuda, Eisuke Nishida; Nuclear Export of Map Kinase (ERK) Involves a Map Kinase Kinase (Mek-Dependent) Active Transport Mechanism. J Cell Biol 6 March 2000; 148 (5): 849–856. doi: https://doi.org/10.1083/jcb.148.5.849
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