Protein kinase Cδ binds TIRAP/Mal to participate in TLR signaling

Toll-like receptor (TLR) family members recognize specific molecular patterns within pathogens. Signaling through TLRs results in a proximal event that involves direct binding of adaptor proteins to the receptors. We observed that TIRAP/Mal, an adaptor protein for TLR2 and TLR4, binds protein kinase C delta (PKC delta). TIRAP/Mal GST-fusion protein and a TIRAP/Mal antibody were able to precipitate PKC delta from rat peritoneal macrophage and THP1 cell lysates. Truncation mutants of TIRAP/Mal showed that the TIR domain of TIRAP/Mal is responsible for binding. TLR2- and TLR4-mediated phosphorylation of p38 MAPK, IKK, and IKB in RAW264.7 cells were abolished by depletion of PKC delta. These results suggest that PKC delta binding to TIRAP/Mal promotes TLR signaling events. (c) 2006 Elsevier Ltd. All rights reserved.