PMID- 10508167
OWN - NLM
STAT- MEDLINE
DCOM- 19991202
LR  - 20161124
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 19
DP  - 1999 Oct 1
TI  - Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of
      a monomer and active transport of a dimer.
PG  - 5347-58
AB  - In response to extracellular stimuli, mitogen-activated protein kinase (MAPK,
      also known as ERK) translocates from the cytoplasm to the nucleus. MAP kinase
      kinase (MAPKK, also know as MEK), which possesses a nuclear export signal (NES), 
      acts as a cytoplasmic anchor of MAPK. Here we show evidence that tyrosine (Tyr190
      in Xenopus MPK1/ERK2) phosphorylation of MAPK by MAPKK is necessary and
      sufficient for the dissociation of the MAPKK-MAPK complex, and that the
      dissociation of the complex is required for the nuclear translocation of MAPK. We
      then show that nuclear entry of MAPK through a nuclear pore occurs via two
      distinct mechanisms. Nuclear import of wild-type MAPK (mol. wt 42 kDa) was
      induced by activation of the MAPK pathway even in the presence of wheat germ
      agglutinin or dominant-negative Ran, whereas nuclear import of beta-galactosidase
      (beta-gal)-fused MAPK (mol. wt 160 kDa), which occurred in response to stimuli,
      was completely blocked by these inhibitors. Moreover, while a
      dimerization-deficient mutant of MAPK was able to translocate to the nucleus upon
      stimulation, this mutant MAPK, when fused to beta-gal, became unable to enter the
      nucleus. These results suggest that monomeric and dimeric forms of MAPK enter the
      nucleus by passive diffusion and active transport mechanisms, respectively.
FAU - Adachi, M
AU  - Adachi M
AD  - Department of Biophysics, Graduate School of Science, Kyoto University, Japan.
FAU - Fukuda, M
AU  - Fukuda M
FAU - Nishida, E
AU  - Nishida E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA Primers)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Recombinant Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - Y031I2N1EO (leptomycin B)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport, Active
MH  - Cell Line
MH  - Cell Nucleus/drug effects/*metabolism
MH  - DNA Primers
MH  - Diffusion
MH  - Dimerization
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Phosphorylation
MH  - Recombinant Proteins/metabolism
MH  - Tyrosine/metabolism
MH  - Xenopus
PMC - PMC1171604
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - 10.1093/emboj/18.19.5347 [doi]
PST - ppublish
SO  - EMBO J. 1999 Oct 1;18(19):5347-58. doi: 10.1093/emboj/18.19.5347.