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Deamidation of Cdc42 and Rac by Escherichia coli Cytotoxic Necrotizing Factor 1: Activation of c-Jun N-Terminal Kinase in HeLa Cells
Open accessAbstract
Recently, Escherichia coli cytotoxic necrotizing factor 1 (CNF1) was shown to activate the low-molecular-mass GTPase RhoA by deamidation of Gln63, thereby inhibiting intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities (G. Schmidt, P. Sehr, M. Wilm, J. Selzer, M. Mann, and K. Aktories, Nature 387:725–729, 1997; G. Flatau, E. Lemichez, M. Gauthier, P. Chardin, S. Paris, C. Fiorentini, and P. Boquet, Nature 387:729–733, 1997). Here we report that in addition to RhoA, Cdc42 and Rac also are targets for CNF1 in vitro and in intact cells. Treatment of HeLa cells with CNF1 induced a transient formation of microspikes and formation of membrane ruffles. CNF1 caused a transient 10- to 50-fold increase in the activity of the c-Jun N-terminal kinase. Tryptic peptides of Cdc42 obtained from CNF1-treated cells by immunoprecipitation exhibited an increase in mass of 1 Da compared to control peptides, indicating the deamidation of glutamine 61 by the toxin. The same increase in mass was observed with the respective peptides obtained from CNF1-modified recombinant Cdc42 and Rac1. Modification of recombinant Cdc42 and Rac1 by CNF1 inhibited intrinsic and GAP-stimulated GTPase activities and retarded binding of 2′(3′)- O-(N -methylanthraniloyl)GDP. The data suggest that recombinant as well as cellular Cdc42 and Rac are substrates for CNF1.
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Cites
Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation
Khosravi-Far, R., Solski, P. A., Clark, G. J., Kinch, M. S., & Der, C. J. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.11.6443 · Cited by 683
Cited by
Kaper, J. B., Nataro, J. P., & Mobley, H. L. T. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro818 · Cited by 5,583
Segal, E. D., Cha, J., Lo, J., Falkow, S., & Tompkins, L. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14559 · Cited by 770
Daub, H., Gevaert, K., Vandekerckhove, J., Sobel, A., & Hall, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c000635200 · Cited by 295
Doye, A., Mettouchi, A., Bossis, G., Clément, R., Buisson-Touati, C., Flatau, G., Gagnoux, L., Piechaczyk, M., Boquet, P., & Lemichez, E. (2002) · Cell · doi:10.1016/s0092-8674(02)01132-7 · Cited by 288
Chung, J. W., Hong, S. J., Kim, K. J., Goti, D., Stins, M. F., Shin, S., Dawson, V. L., Dawson, T. M., & Kim, K. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301028200 · Cited by 127
Metadata
- Authors
- Lerm, M., Selzer, J., Hoffmeyer, A., Rapp, U. R., Aktories, K., & Schmidt, G.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 1999-02
- Volume
- 67
- Issue
- 2
- Pages
- 496-503
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- OpenAlex
- W1958495494
- Cited by
- 179
- References
- 1
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Deamidation of Cdc42 and Rac by Escherichia coli Cytotoxic Necrotizing Factor 1: Activation of c-Jun N-Terminal Kinase in HeLa Cells. https://app.cochat.ai/papers/10.1128/iai.67.2.496-503.1999
- The paper
- Lerm, M., Selzer, J., Hoffmeyer, A., Rapp, U. R., Aktories, K., & Schmidt, G. (1999). Deamidation of Cdc42 and Rac by Escherichia coli Cytotoxic Necrotizing Factor 1: Activation of c-Jun N-Terminal Kinase in HeLa Cells. Infection and Immunity. https://doi.org/10.1128/iai.67.2.496-503.1999
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