TIRAP (D6M9Z) Rabbit mAb #13077

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adapter proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adapter-like/TIR-associated protein (MAL/TIRAP), TIR domain-containing adapter-inducing IFN-β (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.

Toll/interleukin-1 receptor domain-containing adaptor protein (TIRAP, MAL) is a cytoplasmic protein containing an amino-terminal PIP2 binding site and a carboxy-terminal TIR domain. This adaptor protein mediates downstream signaling from associated toll-like receptors and is essential for MyD88-dependent TLR2 and TLR4 signaling (9,15-18). TIRAP is recruited to the plasma membrane by its PIP2 binding domain, where it mediates recruitment of MyD88 to initiate TLR signaling (15).