The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4
Open accessAbstract
Toll-like receptor 4 (TLR4), the principal signaling receptor for lipopolysaccharide (LPS) in mammals, requires the binding of MD-2 to its extracellular domain for maximal responsiveness. MD-2 contains a leader sequence but lacks a transmembrane domain, and we asked whether it is secreted into the medium as an active protein. As a source of secreted MD-2 (sMD-2), we used culture supernatants from cells stably transduced with epitope-tagged human MD-2. We show that sMD-2 exists as a heterogeneous collection of large disulfide-linked oligomers formed from stable dimeric subunits and that concentrations of sMD-2 as low as 50 pM enhance the responsiveness of TLR4 reporter cells to LPS. An MD-2-like activity is also released by monocyte-derived dendritic cells from normal donors. When coexpressed, TLR4 indiscriminately associates in the endoplasmic reticulum/cis Golgi with different-sized oligomers of MD-2, and excess MD-2 is secreted into the medium. We conclude that normal and transfected cells secrete a soluble form of MD-2 that binds with high affinity to TLR4 and that could play a role in regulating responses to LPS and other pathogen-derived substances in vivo.
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Cites
Intracellular Functions of N-Linked Glycans
Helenius, A., & Aebi, A. M. (2001) · Science · doi:10.1126/science.291.5512.2364 · Cited by 2,405
Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., & Gusovsky, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10689 · Cited by 1,924
Cited by
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Stewart, C. R., Stuart, L. M., Wilkinson, K., van Gils, J. M., Deng, J., Halle, A., Rayner, K. J., Boyer, L., Zhong, R., Frazier, W. A., et al. (2010) · Nature Immunology · doi:10.1038/ni.1836 · Cited by 1,513
“We therefore tested whether fibrillar β-amyloid peptide (1-42) (Aβ1-42) could activate TLR4-TLR6 signaling via CD36.”
BackgroundSignal transduction by the lipopolysaccharide receptor, Toll-like receptor-4
Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01976.x · Cited by 1,254
LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF
Fitzgerald, K. A., Rowe, D. C., Barnes, B. J., Caffrey, D. R., Visintin, A., Latz, E., Monks, B., Pitha, P. M., & Golenbock, D. T. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031023 · Cited by 1,193
Self-citationEssential role of MD-2 in LPS responsiveness and TLR4 distribution
Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., Kitamura, T., Kosugi, A., Kimoto, M., & Miyake, K. (2002) · Nature Immunology · doi:10.1038/ni809 · Cited by 1,020
Metadata
- Authors
- Visintin, A., Mazzoni, A., Spitzer, J. A., & Segal, D. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-10-02
- Volume
- 98
- Issue
- 21
- Pages
- 12156-12161
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2088834687
- Cited by
- 230
- References
- 2
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- green
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- Visintin, A., Mazzoni, A., Spitzer, J. A., & Segal, D. M. (2001). Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.211445098
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