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Diphtheria Toxin Binds to the Epidermal Growth Factor (EGF)-like Domain of Human Heparin-binding EGF-like Growth Factor/Diphtheria Toxin Receptor and Inhibits Specifically Its Mitogenic Activity
Open accessAbstract
The membrane anchored form of human heparin-binding epidermal growth factor-like growth factor (HB-EGF) acts as the diphtheria toxin (DT) receptor. Transfection of human HB-EGF cDNA into mouse LC cells, L cells stably expressing DRAP27, conferred sensitivity to DT, but transfection of mouse HB-EGF cDNA did not. To define the essential regions of HB-EGF that serve as the functional DT receptor, we examined the sensitivity to DT and DT binding of cells expressing several human/mouse HB-EGF chimeras. It was found that DT binds to the EGF-like domain of the human HB-EGF. However, mouse HB-EGF does not serve as a functional DT receptor due to non-conserved amino acid substitutions in this domain. In addition, CRM197, a non-toxic mutant of DT, inhibited strongly the mitogenic activity of the secreted form of human HB-EGF, but not of mouse HB-EGF and other EGF receptor-binding growth factors. These results confirmed further that DT interacts with the EGF-like domain of HB-EGF and that this interaction is specific for human HB-EGF.
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Higashiyama, S., Lau, K., Besner, G. E., Abraham, J. A., & Klagsbrun, M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42682-8 · Cited by 349
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Metadata
- Authors
- Mitamura, T., Higashiyama, S., Taniguchi, N., Klagsbrun, M., & Mekada, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-01
- Volume
- 270
- Issue
- 3
- Pages
- 1015-1019
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1993223505
- Cited by
- 306
- References
- 1
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Diphtheria Toxin Binds to the Epidermal Growth Factor (EGF)-like Domain of Human Heparin-binding EGF-like Growth Factor/Diphtheria Toxin Receptor and Inhibits Specifically Its Mitogenic Activity. https://app.cochat.ai/papers/10.1074/jbc.270.3.1015
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- Mitamura, T., Higashiyama, S., Taniguchi, N., Klagsbrun, M., & Mekada, E. (1995). Diphtheria Toxin Binds to the Epidermal Growth Factor (EGF)-like Domain of Human Heparin-binding EGF-like Growth Factor/Diphtheria Toxin Receptor and Inhibits Specifically Its Mitogenic Activity. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.270.3.1015
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