Abstract
Because there are several nuclear substrates for the members of the mitogen-activated protein kinase (MAPK) superfamily, they should become localized to the nucleus to achieve their functions. For example, whereas extracellular signal-regulated kinase (ERK) predominantly localizes to the cytoplasm in quiescent cells, it translocates to the nucleus upon its activation by mitogenic stimuli (1–3). Nuclear localization of ERK is transient, however, and ERK is exported from the nucleus to the cytoplasm when it is inactivated. Similarly, ultraviolet irradiation and osmotic stimuli induce activation and transient nuclear localization of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38 MAPKs (4–6). To adequately perform their functions, not only the activation state but also the subcellular localization must be tightly regulated.
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References
Chen, R.-H., Sarnecki, C., and Blenis, J. (1992) Nuclear localization and regulation of erk-and rsk-encoded protein kinases. Mol. Cell. Biol. 12, 915–927.
Gonzalez, F. A., Seth, A., Raden, D. L., Bowman, D. S., Fay, F. S., and Davis, R. J. (1993) Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus. J. Cell Biol. 122, 1089–1101.
Lenormand, P., Sardet, C., Pages, G., ĽAllemain, G., Brunet, A., and Pouyssegur, J. (1993) Growth factors induce nuclear translocation of MAP kinases (p42mapk and p44mapk) but not their activator MAP kinase kinase (p45mapkk) in fibroblasts. J. Cell Biol. 122, 1079–1088.
Cavigelli, M., Dolfi, F., Claret, F. X., and Karin, M. (1995) Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation. EMBO J. 14, 5957–5964.
Kawasaki, H., Moriguchi, T., Matsuda, S., et al. (1996) Ras-dependent and Rasindependent activation pathways for the stress-activated-protein-kinase cascade. Eur. J. Biochem. 241, 315–321.
Cheng, H. L. and Feldman, E. L. (1998) Bidirectional regulation of p38 kinase and c-Jun N-terminal protein kinase by insulin-like growth factor-I. J. Biol. Chem. 273, 14,560–14,565.
Fukuda, M., Gotoh, Y., and Nishida, E. (1997) Interaction of MAP kinase with MAP kinase kinase: its possible role in the control of nucleocytoplasmic transport of MAP kinase. EMBO J. 16, 1901–1908.
Rubinfeld, H., Hanoch, T., and Seger, R. (1999) Identification of a cytoplasmicretention sequence in ERK2. J. Biol. Chem. 274, 30,349–30,352.
Tanoue, T., Adachi, M., Moriguchi, T., and Nishida, E. (2000) A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nature Cell Biol. 2, 110–116.
Fukuda, M., Gotoh, I., Gotoh, Y., and Nishida, E. (1996) Cytoplasmic localization of MAP kinase kinase directed by its N-terminal, leucine-rich short amino acid sequence, which acts as a nuclear export signal. J. Biol. Chem. 271, 20,024–20,028.
Adachi, M., Fukuda, M., and Nishida, E. (1999) Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimer. EMBO J. 18, 5347–5358.
Khokhlatchev, A. V., Canagarajah, B., Wilsbacher, J., et al. (1998) Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation. Cell 93, 605–615.
Lenormand, P., Brondello, J. M., Brunet, A., and Pouyssegur, J. (1998) Growth factor-induced p42/p44 MAPK nuclear translocation and retention requires both MAPK activation and neosynthesis of nuclear anchoring proteins. J. Cell Biol. 142, 625–633.
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.
Gaits, F., Degols, G., Shiozaki, K., and Russel, P. (1998) Phosphorylation and association with the transcription factor Atf1 regulate localization of Spc1/Sty1 stress-activated kinase in fission yeast. Genes Dev. 12, 1464–1473.
Ferrell, J. E., Jr. (1996) Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends Biochem. Sci. 21, 460–466.
Lorenzen, J. A., Baker, S. E., Denhez, F., Melnick, M. B., Brower, D. L., and Perkins, L. A. (2001) Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin. Development 128, 1403–1414.
Kim-Kaneyama, J., Nose, K., and Shibanuma, M. (2000) Significance of nuclear relocalization of ERK1/2 in reactivation of c-fos transcription and DNA synthesis in senescent fibroblasts. J. Biol. Chem. 275, 20,685–20,692.
Lim, I. K., Hong, K. W., Kwak, I. H., Yoon, G., and Park, S. C. (2000) Cytoplasmic retention of p-Erk1/2 and nuclear accumulation of actin proteins during cellular senescence in human diploid fibroblasts. Mech. Ageing Dev. 119, 113–129.
Aplin, A. E., Stewart, S. A., Assoian, R. K., and Juliano, R. L. (2001) Integrinmediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1. J. Cell Biol. 153, 273–281.
Fincham, V. J., James, M., Frame, M. C., and Winder, S. J. (2000) Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBO J. 19, 2911–2923.
Pritchard, C. A., Samuels, M. L., Bosch, E., and McMahon, M. (1995) Conditionally oncogenic forms of the A-Raf and B-Raf protein kinases display different biological and biochemical properties in NIH 3T3 cells. Mol. Cell. Biol. 15, 6430–6442.
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© 2004 Humana Press Inc., Totowa, NJ
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Adachi, M., Nishida, E. (2004). Subcellular Localization of MAPKs. In: Seger, R. (eds) MAP Kinase Signaling Protocols. Methods in Molecular Biology™, vol 250. Humana Press. https://doi.org/10.1385/1-59259-671-1:145
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DOI: https://doi.org/10.1385/1-59259-671-1:145
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