Editors' ChoiceProtein Shuttling

Resolving an Erk-some Dilemma

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Science's STKE  21 Mar 2000:
Vol. 2000, Issue 24, pp. tw7
DOI: 10.1126/stke.2000.24.tw7

Activation of mitogen-activated protein kinases (MAPKs) and MAPK kinases (MEKs) leads to their translocation from the cytoplasm to the nucleus. Once the transduced signal has abated, the kinases shuttle back to the cytoplasm. However, MAPKs do not appear to have nuclear export signal (NES) motifs coded within their amino acid sequences. Adachi et al. resolve this enigma by showing that MAPK binds to MEK in the nucleus, and both utilize the NES motif found on MEK to relocalize to the cytoplasm. The nuclear export of MAPK was blocked by the specific NES inhibitor leptomycin B. Also, when injected into the nucleus, MAPK relocalized to the cytoplasm with coinjected MEK, but not with a MEK mutant in which the NES was disrupted. Finally, nuclear injection of a protein fragment that includes the MAPK-binding site on MEK decreased MAPK export. Thus, transport of MAPK from the nucleus to the cytoplasm appears to require association of MAPK with MEK.

Adachi, M., Fukuda, M., and Nishida, E. (2000) Nuclear export of MAP kinase (ERK) involves a MAP kinase kinase (MEK)-dependent active transport mechanism. J. Cell Biol. 148: 849-856. [Abstract] [Full Text]

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