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Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase
Abstract
Mitogen-activated protein (MAP) kinase kinase (MAPKK) activates MAP kinase in a signal transduction pathway that mediates cellular responses to growth and differentiation factors. Oncogenes such as ras , src , raf , and mos have been proposed to transform cells by prolonging the activated state of MAPKK and of components downstream in the signaling pathway. To test this hypothesis, constitutively active MAPKK mutants were designed that had basal activities up to 400 times greater than that of the unphosphorylated wild-type kinase. Expression of these mutants in mammalian cells activated AP-1-regulated transcription. The cells formed transformed foci, grew efficiently in soft agar, and were highly tumorigenic in nude mice. These findings indicate that constitutive activation of MAPKK is sufficient to promote cell transformation.
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Citations
Cited by
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 3,906
Whitmarsh, A. J., & Davis, R. J. (1996) · Journal of Molecular Medicine · doi:10.1007/s001090050063 · Cited by 1,543
The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway
Coso, O. A., Chiariello, M., Yu, J.-C., Teramoto, H., Crespo, P., Xu, N., Miki, T., & Silvio Gutkind, J. (1995) · Cell · doi:10.1016/s0092-8674(05)80018-2 · Cited by 1,397
Phosphorylation and Functional Inactivation of TSC2 by Erk
Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945
Metadata
- Authors
- Mansour, S. J., Matten, W. T., Hermann, A. S., Candia, J. M., Rong, S., Fukasawa, K., Vande Woude, G. F., & Ahn, N. G.
- Venue
- Science
- Published
- 1994-08-12
- Volume
- 265
- Issue
- 5174
- Pages
- 966-970
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2001521752
- Cited by
- 1,353
- References
- 0
- FWCI
- 30.52
- Type
- journal article
- Language
- en
- Open access
- closed
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- Mansour, S. J., Matten, W. T., Hermann, A. S., Candia, J. M., Rong, S., Fukasawa, K., Vande Woude, G. F., & Ahn, N. G. (1994). Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase. Science. https://doi.org/10.1126/science.8052857
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