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A Novel Regulatory Mechanism in the Mitogen-activated Protein (MAP) Kinase Cascade
Open accessAbstract
Mitogen-activated protein kinase (MAPK) kinase (MAPKK, also known as MEK), a direct activator for MAPK/extracellular signal-regulated kinase, localizes to the cytoplasm excluded from the nucleus during signal transmission. This nuclear exclusion of MAPKK is directed by its nuclear export signal (NES), but its physiological significance has been unknown. We have found that disruption of the NES dramatically potentiates the ability of constitutively active MAPKK to induce morphological changes and malignant transformation of fibroblastic cells. Readdition of the NES sequence reversed the effects induced by the NES disruption. Moreover, we observed that a dramatic increase of activated MAPK in the nucleus was induced by the NES-disrupted MAPKK and that coexpression of MAPK phosphatase-1 (CL-100) or a kinase negative form of MAPK counteracted the phenotypes induced by the NES-disrupted MAPKK, indicating the crucial role of MAPK in the responses. These findings reveal a novel regulatory role of the NES of MAPKK that may be essential for proper signal transductions.
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Sun, H., Charles, C. H., Lau, L. F., & Tonks, N. K. (1993) · Cell · doi:10.1016/0092-8674(93)90383-2 · Cited by 1,156
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Metadata
- Authors
- Fukuda, M., Gotoh, I., Adachi, M., Gotoh, Y., & Nishida, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-12
- Volume
- 272
- Issue
- 51
- Pages
- 32642-32648
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1980303501
- Cited by
- 181
- References
- 1
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Fukuda, M., Gotoh, I., Adachi, M., Gotoh, Y., & Nishida, E. (1997). A Novel Regulatory Mechanism in the Mitogen-activated Protein (MAP) Kinase Cascade. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.272.51.32642
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
