PKC isoforms act at many levels in TLR signaling. PKC-α associates with the TLR2 signaling complex in a MyD88-dependent manner. PKC-α is also required for TLR3-mediated IRF-3 binding to CBP and IFN-β gene induction. Interaction of PKC-δ with TIRAP is required for the downstream activation of NF-κB. PKC-ε associates with complexes of MyD88 and TLR2 or TLR4 and is necessary for downstream signaling. PKC-ε is also required for the phosphorylation of TRAM. PKC-ζ is activated upon ligation of TLR2 or TLR4. During signaling by these receptors, active PKC-ζ binds to TLR2, associates with TRAF6 and RhoA, and is required for full transcriptional activation of p65.
