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Publication : TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway.

First Author  Yamamoto M Year  2003
Journal  Nat Immunol Volume  4
Issue  11 Pages  1144-50
PubMed ID  14556004 Mgi Jnum  J:86256
Mgi Id  MGI:2679164 Doi  10.1038/ni986
Citation  Yamamoto M, et al. (2003) TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 4(11):1144-50
abstractText  Recognition of pathogens by Toll-like receptors (TLRs) triggers innate immune responses through signaling pathways mediated by Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88, TIRAP and TRIF. MyD88 is a common adaptor that is essential for proinflammatory cytokine production, whereas TRIF mediates the MyD88-independent pathway from TLR3 and TLR4. Here we have identified a fourth TIR domain-containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed its physiological function by gene targeting. TRAM-deficient mice showed defects in cytokine production in response to the TLR4 ligand, but not to other TLR ligands. TLR4- but not TLR3-mediated MyD88-independent interferon-beta production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling.
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