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

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.

IRAК2被证实在IL1R和TLR信号通路中发挥作用，这一发现源于IRAК2能够与MyD88和Mal（Muzio等，1997年）结合的事实。与IRAК1类似，IRAК2在IRAК4下游被激活（Kawagoe等，2008年）。有研究表明IRAК1可以激活IRAК2（Wesche等，1999年），但IRAК2的磷酸化在IRAК1–/–小鼠巨噬细胞中观察到，而IRAК4的缺乏则阻断了IRAК2的磷酸化（Kawagoe等，2008年），这表明激活的IRAК4如同对IRAК1那样，磷酸化IRAК2。对IL1beta的反应中，胚胎成纤维细胞中IL6的产生在IRAК1或IRAК2敲除小鼠中受损，并在IRAК1/2双重敲除小鼠中完全阻断（Kawagoe等，2007年），这表明IRAК1和IRAК2均参与IRAК4下游的IL1R信号通路。