IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:TIRAP complex

Stable Identifier
R-HSA-166091
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Neisseria meningitidis serogroup B, Chlamydia trachomatis
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IRAK1 is recruited to the TLR complex through binding with IRAK4[Lin SC et al 2010].

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
17878161 IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination

Keating, SE, Maloney, GM, Moran, EM, Bowie, AG

J Biol Chem 2007
21606490 Human interleukin-1 receptor-associated kinase-2 is essential for Toll-like receptor-mediated transcriptional and post-transcriptional regulation of tumor necrosis factor alpha

Flannery, SM, Keating, SE, Szymak, J, Bowie, AG

J. Biol. Chem. 2011
17890055 IRAK1: a critical signaling mediator of innate immunity

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

Cell Signal 2008
20485341 Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling

Lin, SC, Lo, YC, Wu, H

Nature 2010
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
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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