Reactome | IRAK2 is phosphorylated downstream of IRAK4 following IL1 receptor activation

IRAK2 is phosphorylated downstream of IRAK4 following IL1 receptor activation

Stable Identifier

R-HSA-446684

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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IRAK2 is phosphorylated downstream of IRAK4 following IL1 receptor activation

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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.

Literature References

PubMed ID	Title	Journal	Year
18438411	Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2 Kumagai, Y, Kawai, T, Takeuchi, O, Saitoh, T, Matsushita, K, Sato, S, Akira, S, Matsui, K, Kato, H, Kawagoe, T	Nat Immunol	2008