description
The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects

external resources
NCBI:1269237
REACTOME:R-HSA-166058
PUBMED:15276183

genes
AGER , APP , ATF1 , BTK , CD14 , CD36 , CHUK , MAP3K8 , CREB1 , ATF2 , MAPK14 , DHX9 , DUSP3 , DUSP4 , DUSP6 , DUSP7 , ELK1 , FOS , HMGB1 , IKBKB , IRAK1 , IRAK2 , JUN , MEF2A , MEF2C , MAP3K1 , MYD88 , NFKB1 , NFKB2 , NFKBIA , NFKBIB , PPP2CA , PPP2CB , PPP2R1A , PPP2R1B , PPP2R5D , MAPK1 , MAPK3 , MAPK7 , MAPK8 , MAPK11 , MAPK9 , MAPK10 , MAP2K1 , MAP2K3 , MAP2K6 , MAP2K7 , RELA , RPS6KA1 , RPS6KA2 , RPS6KA3 , RPS27A , S100A12 , S100B , SAA1 , MAP2K4 , SKP1 , MAP3K7 , TLR1 , TLR2 , TLR4 , TRAF6 , UBA52 , UBB , UBC , UBE2N , UBE2V1 , MAPKAPK3 , CUL1 , IKBKG , SOCS1 , RIPK2 , BTRC , RPS6KA5 , MAPKAPK2 , TLR6 , NOD1 , TAB1 , IRAK3 , TAB2 , FBXW11 , LY96 , IRAK4 , VRK3 , ECSIT , PELI2 , PELI1 , SIGIRR , NOD2 , TNIP2 , TIRAP , PELI3 , TAB3 , MIR718 ,