Figure 1

Simplified scheme for TLR signaling in enterocytes. TLRs in the cytoplasmic membrane or subcellular compartments such as the endosome bind the MyD88 adapter protein to initiate signaling. MyD88 recruits TRAF6 and members of the IRAK family (IRAKs) which leads to activation of the TAK1 complex (TAK1, TAB1/2). The activated TAK complex then activates the IKK complex (IKKα and IKKβ) which phosphorylates the inhibitor of NF-κB (IKB) leading to its degradation and the translocation of NF-κB (typically p50 and p65 heterodimers) into the nucleus where it activates gene expression. The activated TAK1 complex simultaneously activates the MAPK pathway resulting in phosphorylation (P) and activation of the transcription factor AP1. The canonical pathway of NF-κB activation and can also be triggered by binding of TRAM and TRIF adaptor proteins to TLR4 (not shown). The adaptor protein TRIF which binds to TLR3 recruits TRAF3 which interacts with the TBK and IKKi kinases to promote phosphorylation (P) of IRF3 which translocates to the nucleus and activates transcription of type 1 interferons, especially IFN-β. The NOD1 and 2 receptros activate NK-κB via the serine threonine kinase RICK. This diagram is a modified version of Figure 1 published by Wells et al., 2010 [17].