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MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4
Open accessAbstract
Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.
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Cited by
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S., Takeda, K., & Kaisho, T. (2001) · Nature Immunology · doi:10.1038/90609 · Cited by 4,777
Raetz, C. R. H., & Whitfield, C. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135414 · Cited by 4,404
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308
Metadata
- Authors
- Shimazu, R., Akashi, S., Ogata, H., Nagai, Y., Fukudome, K., Miyake, K., & Kimoto, M.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1999-06-07
- Volume
- 189
- Issue
- 11
- Pages
- 1777-1782
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2095833996
- Cited by
- 2,185
- References
- 0
- FWCI
- 33.43
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shimazu, R., Akashi, S., Ogata, H., Nagai, Y., Fukudome, K., Miyake, K., & Kimoto, M. (1999). MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.189.11.1777
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