hp-IRAK1 or p-IRAK2 bound to the pIRAK4:MyD88:activated TLR7/8 or 9 complex TRAF6:hp-IRAK1/or p-IRAK2:p-IRAK4:oligo-MyD88:activated TLR7/8 or 9 TRAF6 binds to hp- IRAK1/or p-IRAK2:p-IRAK4:MyD88:activated TLR7/8 or 9 Authored: Shamovsky, V, 2010-08-25 Edited: Shamovsky, V, 2010-11-15 Hyperphosphorylated IRAK1, still within the receptor complex, binds TRAF6 through multiple regions including the death domain, the undefined domain and the C-terminal C1 domain (Li et al. 2001). The C-terminal region of IRAK-1 contains three potential TRAF6-binding sites; mutation of the amino acids (Glu544, Glu587, Glu706) in these sites to alanine greatly reduces activation of NFkappaB (Ye et al. 2002). IRAK-2 has two TRAF6 binding motifs that are responsible for initiating TRAF6 signaling transduction (Ye H et al 2002). IRAK2 point mutants with mutated TRAF6-binding motifs abrogate NFkB activation and are incapable to stimulate TRAF6 ubiquitination (Keating SE et al 2007). Pubmed11287640 Pubmed12138165 Pubmed12140561 Pubmed17878161 Pubmed18070982 Pubmed8837778 Reactome Database ID Release 43975111 Reactome, http://www.reactome.org ReactomeREACT_25150 Reviewed: Gillespie, ME, 2010-10-29 has a Stoichiometric coefficient of 4