Pathway Map Details

Immune response_TLR3 and TLR4 induce TICAM1-specific signaling pathway

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NF-kB, double-stranded RNA, RIPK3, IFN-beta, MD-2, IRF3, TLR3, TIRAP (Mal), TRIF (TICAM1), polyinosinic' polycytidylic acid, LPS, Paclitaxel cytosol, RIPK1, TRAF6, CD14, TRAM, IKK-gamma, IFN-alpha, TLR4


Role of TLRs 3 and 4 in cell antiviral response: TICAM1-specific signaling pathways

Toll-like receptors ( TLR ) initiate signaling cascades through recognition of a variety of microbial components, thus serving as an important link between innate and adaptive immune responses. Each TLR recognizes distinct ligands by means of its leucine-rich repeats and elicits different, but often overlapping immune responses [1].

TLR3 -induced signaling pathways are triggered by binding of virus-derived double-stranded RNA [1], whereas TLR4 becomes activated after binding to number of bacterial cell wall components: Lipopolysaccharide ( LPS ) [1], Pulmonary surfactant-associated protein A ( PSAP ) [2], Paclitaxel [3], Fibronectin [4], Pneumolysin [5].

Although Myeloid differentiation primary response gene 88 ( MyD88 )-dependent signaling pathway is common for all TLR s, TLR3 - and TLR4 -induced activation of the transcription factor nuclear factor kappa B ( NF-kB ) can be mediated by some alternative adaptors. It can be activated by TLR3 ligands via Toll-like receptor adaptor molecule 1 ( TRIF (TICAM1) ) [1]. TLR4 signaling can also be mediated by TRIF (TICAM1), which binds to TLR4 adaptor Toll-like receptor adaptor molecule 2 ( TRAM ) [6]. TLR4 activates NF-kB independently of TRIF (TICAM1) through its other adaptor, Toll-interleukin 1 receptor domain containing adaptor protein ( TIRAP (Mal) ) [7]. TRIF (TICAM1) -dependent NF-kB activation is mediated either by TNF receptor-associated factor 6 ( TRAF6 ) or by Receptor TNFRSF-interacting serine-threonine kinase 1 ( RIPK1 )-induced kinase cascade [1]. Moreover, TRIF (TICAM1) causes activation of transcription factor Interferon regulatory factor 3 ( IRF3 ) [8]. Both IRF3 and NF-kB regulate expression of such proinflammatory molecules as Interferon alpha and beta ( IFN-alpha and IFN-beta ), thus mediating the antiviral action of interferon.


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