Figure 7.

Model of negative regulation of SIK1 and SIK3 in TLR4-mediated signaling. A, Upon the TLR4 stimulation, TAB2 interacts with C terminus of TAK1 and simultaneously interacts with TRAF6 through the N terminus of TAB2. The interaction of TAB2 to TAK1 and TRAF6 regulates TAK1 activity and facilitates TRAF6 ubiquitination, respectively, and that induces the activation of NF-κB. B, If intracellular SIK1 or SIK3 preferentially interacts with TAB2 through its N terminus, the interaction inhibits the association with TRAF6 to TAB2. Molecular inhibition between TAB2 and TRAF6 cause prevention of polyubiquitination of TRAF6 and TAB2, and that inhibits downstream signals for the activation of NF-κB.