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Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor
Abstract
Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors.
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Citations
Cited by
Signal transduction by the JNK group of MAP kinases
Davis, R. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00116-1 · Cited by 4,237
Inflammasomes and Their Roles in Health and Disease
Lamkanfi, M., & Dixit, V. M. (2012) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101011-155745 · Cited by 935
Mock, M., & Fouet, A. (2001) · Annual Review of Microbiology · doi:10.1146/annurev.micro.55.1.647 · Cited by 894
Dixon, T. C., Meselson, M., Guillemin, J., & Hanna, P. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199909093411107 · Cited by 874
A conserved docking motif in MAP kinases common to substrates, activators and regulators
Tanoue, T., Adachi, M., Moriguchi, T., & Nishida, E. (2000) · Nature Cell Biology · doi:10.1038/35000065 · Cited by 816
Metadata
- Authors
- Duesbery, N. S., Webb, C. P., Leppla, S. H., Gordon, V. M., Klimpel, K. R., Copeland, T. D., Ahn, N. G., Oskarsson, M. K., Fukasawa, K., Paull, K. D., & Vande Woude, G. F.
- Venue
- Science
- Published
- 1998-05
- Volume
- 280
- Issue
- 5364
- Pages
- 734-737
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2101355256
- Cited by
- 1,008
- References
- 0
- FWCI
- 12.16
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor. https://app.cochat.ai/papers/10.1126/science.280.5364.734
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- Duesbery, N. S., Webb, C. P., Leppla, S. H., Gordon, V. M., Klimpel, K. R., Copeland, T. D., Ahn, N. G., Oskarsson, M. K., Fukasawa, K., Paull, K. D., & Vande Woude, G. F. (1998). Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor. Science. https://doi.org/10.1126/science.280.5364.734
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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.
