IRAK1, IRAK2 p-S,2T-IRAK4:oligo-MyD88:Mal:activated TLR receptor IRAK1/or IRAK2:p-IRAK4:MyD88 oligomer:Mal:activated TLR IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:Mal complex Authored: de Bono, B, 2005-08-16 10:54:15 Edited: Shamovsky, V, 2012-11-06 IRAK1 is recruited to the TLR complex through binding with IRAK4[Lin SC et al 2010].<p> IRAK2 has been implicated in IL1R and TLR signaling by the observation that IRAK2 can associate with MyD88 and Mal (Muzio et al. 1997). Like IRAK1, IRAK2 is activated downstream of IRAK4 (Kawagoe et al. 2008). It has been suggested that IRAK1 activates IRAK2 (Wesche et al. 1999) but IRAK2 phosphorylation is observed in IRAK1–/– mouse macrophages while IRAK4 deficiency abrogates IRAK2 phosphorylation (Kawagoe et al. 2008), suggesting that activated IRAK4 phosphorylates IRAK2 as it does IRAK1. IL6 production in response to IL1beta is impaired in embryonic fibroblasts from IRAK1 or IRAK2 knockout mice and abrogated in IRAK1/2 dual knockouts (Kawagoe et al. 2007) suggesting that IRAK1 and IRAK2 are both involved in IL1R signaling downstream of IRAK4. Pubmed12150927 Pubmed16024789 Pubmed17878161 Pubmed17890055 Pubmed18438411 Pubmed19224918 Pubmed20485341 Pubmed21606490 Pubmed9374458 Reactome Database ID Release 43166091 Reactome, http://www.reactome.org ReactomeREACT_6929 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Reviewed: Gillespie, ME, 2010-11-30 Reviewed: Napetschnig, Johanna, 2012-11-16 has a Stoichiometric coefficient of 4