Fig. 5. A working model for MEKK3 function in the LPA-induced IKK-NF-κB activation.
LPA induces PKC activation which in turn induces β-arrestin 2 and CARMA3-mediated ubiquitination of IKK complex via TRAF6/Bcl10/MALT1, as well as MEKK3-mediated IKKβ phosphorylation. IKK complex ubiquitination and phosphorylation coordinatively lead to optimal NF-κB activation.