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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2001-10-10
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pubmed:abstractText |
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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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10196138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10201887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10359581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10679411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10877845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10891475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-10963608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-11123299,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-11160242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-11269317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-11274165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-11435474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9237759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-93282,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9374458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9435236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9625770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9686597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9721852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9734363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9763566,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9851930,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11593030-9989974
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/LY96 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Antigen 96,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12156-61
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11593030-Antigens, Surface,
pubmed-meshheading:11593030-Cell Line,
pubmed-meshheading:11593030-Cell Line, Transformed,
pubmed-meshheading:11593030-Dendritic Cells,
pubmed-meshheading:11593030-Disulfides,
pubmed-meshheading:11593030-Drosophila Proteins,
pubmed-meshheading:11593030-Endoplasmic Reticulum,
pubmed-meshheading:11593030-Humans,
pubmed-meshheading:11593030-Lipopolysaccharides,
pubmed-meshheading:11593030-Lymphocyte Antigen 96,
pubmed-meshheading:11593030-Membrane Glycoproteins,
pubmed-meshheading:11593030-Oligopeptides,
pubmed-meshheading:11593030-Receptors, Cell Surface,
pubmed-meshheading:11593030-Toll-Like Receptor 4,
pubmed-meshheading:11593030-Toll-Like Receptors
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pubmed:year |
2001
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pubmed:articleTitle |
Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4.
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pubmed:affiliation |
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA.
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pubmed:publicationType |
Journal Article
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