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TLR4 is activated mainly through the myeloid differentiation factor 88 (MyD88) signaling pathway. MyD88 is a common connector molecule that activates the inflammatory response. Before ligand-induced signaling occurs, TLR4 first needs to associate with its extracellular binding partner, myeloid differentiation factor 2 (MD-2) [41, 42]. The TLR4-MD-2 complex, on binding to the ligand, may recruit another TLR4-MD-2 pair and create a homo-dimeric state [40]. Then, the receptor multimer transmits intracellular signals by the TIR structural domain of TLR4 [43, 44]. TLR4-MD2 dimerization recruits TIR domain-containing adaptor protein (TIRAP) and MyD88. Signals from MyD88 are transmitted to the interleukin-1 receptor-associated kinase (IRAK) family of protein kinases via the interaction between MyD88 and the IRAK4 death domain [45] to recruit the tumor necrosis factor receptor-associated factor 6 (TRAF-6)[46–48].
TRAF6 triggers the activation of a complex composed of transforming growth factor-β-activated kinase (TAK1), One part of the TAK1 pathway is the activation of the IκB kinase (IKK) complex, which is an inhibitor of NF-κB.
TLR4 is activated mainly through the myeloid differentiation factor 88 (MyD88) signaling pathway. MyD88 is a common connector molecule that activates the inflammatory response. Before ligand-induced signaling occurs, TLR4 first needs to associate with its extracellular binding partner, myeloid differentiation factor 2 (MD-2) [41, 42]. The TLR4-MD-2 complex, on binding to the ligand, may recruit another TLR4-MD-2 pair and create a homo-dimeric state [40]. Then, the receptor multimer transmits intracellular signals by the TIR structural domain of TLR4 [43, 44]. TLR4-MD2 dimerization recruits TIR domain-containing adaptor protein (TIRAP) and MyD88. Signals from MyD88 are transmitted to the interleukin-1 receptor-associated kinase (IRAK) family of protein kinases via the interaction between MyD88 and the IRAK4 death domain [45] to recruit the tumor necrosis factor receptor-associated factor 6 (TRAF-6)[46–48].
TRAF6 triggers the activation of a complex composed of transforming growth factor-β-activated kinase (TAK1), One part of the TAK1 pathway is the activation of the IκB kinase (IKK) complex, which is an inhibitor of NF-κB.
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