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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2008-3-19
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pubmed:abstractText |
Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively. How TLR4 coordinates the activation of these two pathways is unknown. Here we show that TLR4 activated these two signaling pathways sequentially in a process organized around endocytosis of the TLR4 complex. We propose that TLR4 first induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from early endosomes. Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta,
http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/TICAM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TIRAP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TRAM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1529-2916
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
361-8
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pubmed:dateRevised |
2011-9-22
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pubmed:meshHeading |
pubmed-meshheading:18297073-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:18297073-Amino Acid Motifs,
pubmed-meshheading:18297073-Amino Acid Sequence,
pubmed-meshheading:18297073-Animals,
pubmed-meshheading:18297073-Cell Line,
pubmed-meshheading:18297073-Down-Regulation,
pubmed-meshheading:18297073-Endocytosis,
pubmed-meshheading:18297073-Humans,
pubmed-meshheading:18297073-Interferon-beta,
pubmed-meshheading:18297073-Intracellular Fluid,
pubmed-meshheading:18297073-Membrane Glycoproteins,
pubmed-meshheading:18297073-Membrane Transport Proteins,
pubmed-meshheading:18297073-Mice,
pubmed-meshheading:18297073-Mice, Inbred C57BL,
pubmed-meshheading:18297073-Molecular Sequence Data,
pubmed-meshheading:18297073-Myeloid Differentiation Factor 88,
pubmed-meshheading:18297073-Receptors, Interleukin-1,
pubmed-meshheading:18297073-Signal Transduction,
pubmed-meshheading:18297073-Toll-Like Receptor 4
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pubmed:year |
2008
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pubmed:articleTitle |
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta.
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pubmed:affiliation |
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. jonathan.kagan@childrens.harvard.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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