Fig. 7.

Model for the cross-talk between IKK family members in the MyD88 signaling pathway. K63-pUb chains formed by TRAF6 in response to IL-1 or TLR stimulation bind to TAB2/3–TAK1 and IKKα/β–NEMO–TANK–TBK1/IKKε complexes enabling the sequential activation of the canonical IKKs by TAK1 and then the activation of the IKK-related kinases by the canonical IKKs and by autoactivation, as discussed in the text. The IKK-related kinases then negatively regulate the canonical IKKs by phosphorylating sites that inhibit activity.