TIRAP (TLR2 and TLR4): Proteins and Enzymes

Mammalian Toll-like receptors (TLRs) recognize conserved products of microbial metabolism and activate NF-kappa B and other signaling pathways through the adapter protein MyD88. All TLRs have a Toll/IL-1 receptor (TIR) domain, which is responsible for signal transduction. MyD88 is one such protein that contains a TIR domain. It acts as an adapter, being involved in TLR-2, TLR-4 and TLR-9 signaling. Toll-interleukin 1 receptor (TIR) domain-containing adapter protein (TIRAP) controls activation of MyD88-independent signaling pathways downstream of TLR4. Double-stranded RNA-binding protein kinase PKR is a component of both the TIRAP- and MyD88-dependent signaling pathways (1). It has been demonstrated that TRIF associates with TRAF6 and TBK1 independently, and activates two distinct transcription factors, NF- B and IFN regulatory factor-3, respectively (2). TIRAP is differentially involved in signaling by members of the TLR family and may account for specificity in the downstream signaling of individual TLRs (3).