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Phosphorylated MAPKs translocate into the nucleus

Stable Identifier
Reaction [BlackBoxEvent]
Homo sapiens
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After phosphorylation by MAP2Ks, a proportion of activated MAPK translocates into the nucleus where it activates nuclear targets (reviewed in Roskoski, 2012b). MAPKs, which lack a nuclear localization signal (NLS), may 'piggyback' into the nucleus in complex with other nuclear-targeted proteins or may translocate by virtue of interaction with components of the nuclear pore complex (Brunet et al, 1999; Adachi et al, 1999; Matsubayashi et al, 2001; Whitehurst et al, 2002; Khokhlatchev et al, 1998; reviewed in Roskoski, 2012b). Although dimerization of MAPKs was thought to be critical for nuclear translocation, a number of studies have now challenged the physiological relevance of MAPK dimerization and this remains an area of uncertainty (Lenormand et al, 1993; Chen et al, 1992; Casar et al, 2008; Lidke et al, 2010; Burack and Shaw, 2005; reviewed in Casar et al, 2009; Roskoski, 2012b)

Literature References
PubMed ID Title Journal Year
19279408 ERK dimers and scaffold proteins: unexpected partners for a forgotten (cytoplasmic) task Cell Cycle 2009
9927426 Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry EMBO J. 1999
19920141 ERK nuclear translocation is dimerization-independent but controlled by the rate of phosphorylation J. Biol. Chem. 2010
9604935 Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation Cell 1998
12032311 ERK2 enters the nucleus by a carrier-independent mechanism Proc. Natl. Acad. Sci. U.S.A. 2002
10508167 Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer EMBO J. 1999
15546878 Live Cell Imaging of ERK and MEK: simple binding equilibrium explains the regulated nucleocytoplasmic distribution of ERK J. Biol. Chem. 2005
18775330 Essential role of ERK dimers in the activation of cytoplasmic but not nuclear substrates by ERK-scaffold complexes Mol. Cell 2008
8394845 Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not of their activator MAP kinase kinase (p45mapkk) in fibroblasts J. Cell Biol. 1993
11546808 Evidence for existence of a nuclear pore complex-mediated, cytosol-independent pathway of nuclear translocation of ERK MAP kinase in permeabilized cells J. Biol. Chem. 2001
1545823 Nuclear localization and regulation of erk- and rsk-encoded protein kinases Mol. Cell. Biol. 1992
22569528 ERK1/2 MAP kinases: structure, function, and regulation Pharmacol. Res. 2012
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