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. Author manuscript; available in PMC: 2020 Dec 1.
Published in final edited form as: Pharmacol Res. 2019 Nov 2;150:104502. doi: 10.1016/j.phrs.2019.104502

Fig 3. Toll-like receptor 4 (TLR4) signaling.

Fig 3.

LPS binding induces TLR4 dimerization at the cell surface and activation of MAL and MyD88. This induces phosphorylation of IRAK, which signals through TRAF6 and TAK1, recruiting TAB proteins. This complex signals through MKKs to p38 and JNK to activate CREB and AP-1 transcription factors. The TAK/TAB complex also signals through the IKK complex to activate NFκB. These pathways lead to production of proinflammatory cytokines. LPS binding induces endocytosis of TLR4, activating signaling through TRAM and TRIF to TRAF3. This ultimately activates transcription factor IRF3 and produces type 1 interferons. TRIF also communicates with TRAF6 via RIP1, activating the MKK and NFκB pathways as well.