Figure 10. Model of TNIK's role in JNK and canonical NF-κB signaling.

LMP1 induces the formation of the TNIK complex at its JNK1 and NF-κB-inducing CTAR2 domain. Interaction of TNIK with LMP1 is mediated by TRAF6, which forms an induced complex with TNIK. Also TAB2 and IKKβ are recruited upon activation, whereas TAK1 is permanently complexed with TNIK. In LMP1 signaling, IKKβ recruitment is further enhanced or stabilized by a TRADD-dependent mechanism. TNIK organizes bifurcation of the JNK and NF-κB pathways downstream of TRAF6. Auto-phosphorylation of TNIK likely constitutes an important step in transmitting signals on the NF-κB axis. JNK signaling is triggered at the GCKH domain of TNIK through TAK1/TAB2. Activation of TAK1/TAB2 further involves K63 ubiquitinylation of TRAF6, which has been demonstrated earlier. Also CD40 signals through the TRAF6/TNIK complex to JNK and IKKβ/NF-κB. For more details, see the text.