anti-MYD88 (human), Rabbit Monoclonal (RM306)

TLRs recognize conserved motifs found in various pathogens and mediate defense responses. Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes. 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. Upon activation, TLRs associate with a number of cytoplasmic adaptor proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adaptor-like/TIR-associated protein (MAL/TIRAP), Toll-receptor-associated activator of interferon (TRIF) and Toll-receptor-associated molecule (TRAM). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK. Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm. MyD88 was originally isolated as a myeloid differentiation primary response gene that is rapidly induced upon IL-6 stimulated differentiation of M1 myeloleukemic cells into macrophages. It contains an amino-terminal death domain separated from a carboxyl-terminal TIR domain and functions as an adaptor in TLR/IL-1 receptor signaling. The death domain of MyD88 mediates interactions with the IRAK complex triggering a signaling cascade that includes the activation of NF-κB.