IRAK1/or IRAK2 binds to the activated IRAK4 :oligo MyD88:activated TLR5 or 10 complex

Stable Identifier
R-HSA-975852
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Escherichia coli
Compartment
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MYD88 recruits unphosphorylated, inactive IRAK1 to the IL1 receptor complex.

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.

Literature References
PubMed ID Title Journal Year
19224918 Interleukin-1 receptor-associated kinase 2 is critical for lipopolysaccharide-mediated post-transcriptional control

Wan, Y, Xiao, H, Affolter, J, Kim, TW, Bulek, K, Chaudhuri, S, Carlson, D, Hamilton, T, Mazumder, B, Stark, GR, Thomas, J, Li, X

J Biol Chem 2009
17890055 IRAK1: a critical signaling mediator of innate immunity

Gottipati, S, Rao, NL, Fung-Leung, WP

Cell Signal 2008
16024789 A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in toll/IL-1R-induced inflammatory

Rao, N, Nguyen, S, Ngo, K, Fung-Leung, WP

Mol Cell Biol 2005
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