IRAK1/or IRAK2 binds to the activated IRAK4 :MyD88:activated TLR 7/8 or 9

Stable Identifier
R-HSA-975115
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1, Influenza A virus, Human SARS coronavirus, Severe acute respiratory syndrome coronavirus 2
Compartment
endosome membrane, cytosol
ReviewStatus
5/5
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IRAK1/or IRAK2 binds to the activated IRAK4 :MyD88:activated TLR 7/8 or 9
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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. MYD88 recruits unphosphorylated, inactive IRAK1 to the IL1 receptor complex.
Literature References
PubMed ID Title Journal Year
15767370 Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction

Uematsu, S, Sato, S, Yamamoto, M, Hirotani, T, Kato, H, Takeshita, F, Matsuda, M, Coban, C, Ishii, KJ, Kawai, T, Takeuchi, O, Akira, S

J Exp Med 2005
17890055 IRAK1: a critical signaling mediator of innate immunity

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

Cell Signal 2008
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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Orthologous Events
IRAK2 binds to p-IRAK4:MyD88:activated TLR7 or 21 complex (Gallus gallus)
Authored
Shamovsky, V  (2010-08-25)
Reviewed
Gillespie, ME  (2010-10-29)
Created
Shamovsky, V  (2010-09-22)
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