IRAK2 介导的 TAK1 复合物激活
中文名称
通路描述
尽管 IRAK-1 最初被认为是 IL1R/TLR 信号传导中 TRAF6 激活的关键介质 (Dong W et al. 2006)，但最近的研究表明，IRAK-2 而非 IRAK-1 导致了 TRAF6 多泛素化 (Keating SE et al 2007)。IRAK-2 缺失功能突变体，其 TRAF6 结合位点发生突变，无法激活 NF-kB 并无法刺激 TRAF-6 泛素化 (Keating SE et al 2007)。此外，代理病毒蛋白 A52 被发现与 IRAK-2 和 TRAF6 相互作用，但与 IRAK-1 无关。进一步研究表明，A52 抑制 IRAK-2 功能，而结合 TRAF6 则导致 A52 诱导的 MAPK 激活。A52 对 TLR3-NFkB 轴的强抑制作用也被观察到，这一发现揭示了 IRAK-2 被招募到 TLR3 以激活 NF-kB (Keating SE et al 2007)。因此，A52 可能通过靶向 IRAK-2 抑制 MyD88 独立 TLR3 通路至 NF-kB，尽管它如何参与 TLR3 信号传导尚不清楚。IRAK-2 被证明具有两个 TRAF6 结合位点，负责启动 TRAF6 信号传导转导 (Ye H et al 2002)。
英文描述
IRAK2 mediated activation of TAK1 complex Although IRAK-1 was originally thought to be a key mediator of TRAF6 activation in the IL1R/TLR signaling (Dong W et al. 2006), recent studies showed that IRAK-2, but not IRAK-1, led to TRAF6 polyubiquitination (Keating SE et al 2007). IRAK-2 loss-of-function mutants, with mutated TRAF6-binding motifs, could no longer activate NF-kB and could no longer stimulate TRAF-6 ubiquitination (Keating SE et al 2007). Furthermore, the proxyvirus protein A52 - an inhibitor of all IL-1R/TLR pathways to NF-kB activation, was found to interact with both IRAK-2 and TRAF6, but not IRAK-1. Further work showed that A52 inhibits IRAK-2 functions, whereas association with TRAF6 results in A52-induced MAPK activation. The strong inhibition effect of A52 was also observed on the TLR3-NFkB axis and this observation led to the discovery that IRAK-2 is recruited to TLR3 to activate NF-kB (Keating SE et al 2007). Thus, A52 possibly inhibits MyD88-independent TLR3 pathways to NF-kB via targeting IRAK-2 as it does for other IL-1R/TLR pathways, although it remains unclear how IRAK-2 is involved in TLR3 signaling.IRAK-2 was shown to have two TRAF6 binding motifs that are responsible for initiating TRAF6 signaling transduction (Ye H et al 2002).
所含基因
9 个基因