MyD88-dependent TLR/IL-1R signaling . TLR/IL-R activation leads to the association of MyD88 (myleoid differentiation primary-response protein 88), which can be enhanced by the presence of MAL (MyD88 adaptor-like) (TLR4 signaling only). As a result, IRAK1 and IRAK4 (interleukin-1 receptor-associated kinase) are recruited to the receptor. Following IRAK1 phosphorylation by IRAK4, TRAF6 (TNF receptor associated factor 6) interacts with IRAK1. This leads to the dissociation and relocation of IRAK1, IRAK4, and TRAF6 to the plasma membrane. There, interaction with the complex of TAK1 (TGF-β-activated kinase 1), TAB1 (TAK1-binding protein), and TAB2 leads to the relocation and association of TAK1 to either the IKK (IκB kinase complex) complex or ASK1 (apoptosis signal-regulating kinase 1). Interface with ASK1 results in downstream MAPK signaling leading to AP-1/ATF transcription factor activity, whereas interaction with IKK leads to IκB degradation and NF-κB transcription factor activity.