IkappaB kinase is an essential component of the Tpl2 signaling pathway.
IkappaB kinase is an essential component of the Tpl2 signaling pathway.
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DOI：
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发表时间：
2004
影响因子：
5.3
通讯作者：
M. Waterfield;W. Jin;W. Reiley;Minying Zhang;Shao-Cong Sun
中科院分区：
文献类型：
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作者：
M. Waterfield;W. Jin;W. Reiley;Minying Zhang;Shao-Cong Sun
IkappaB激酶（IKK）是免疫和炎症反应的关键调节因子，被认为是介导转录因子NF-κ B活化的效应激酶。IKK是否也参与其他信号事件尚不清楚。在这里，我们表明，IKK作为一个信号通路，涉及激活Tp 12激酶及其下游目标，MEK 1和ERK的重要组成部分。巨噬细胞中IKK β的抑制消除了脂多糖和肿瘤坏死因子α诱导的Tp 12活化和ERK磷酸化。使用IKK缺陷的鼠成纤维细胞，我们进一步证明了IKK β，而不是IKK α，是Tp 12激活所必需的。此外，IKK β的这种新功能似乎涉及Tp 12抑制剂NF-κ B1/p105的磷酸化和降解。这些发现表明IKK β通过靶向不同的下游信号通路发挥其免疫调节功能。
IkappaB kinase (IKK), a key regulator of immune and inflammatory responses, is known as an effector kinase mediating activation of the transcription factor NF-kappaB. Whether IKK also participates in other signaling events is not known. Here we show that IKK serves as an essential component of a signaling pathway that involves activation of the Tpl2 kinase and its downstream targets, MEK1 and ERK. Inhibition of IKKbeta in macrophages eliminates Tpl2 activation and ERK phosphorylation induced by lipopolysaccharide and tumor necrosis factor alpha. Using IKK-deficient murine fibroblasts, we further demonstrate that IKKbeta, but not IKKalpha, is required for Tpl2 activation. Moreover, this novel function of IKKbeta appears to involve phosphorylation and degradation of the Tpl2 inhibitor NF-kappaB1/p105. These findings suggest that IKKbeta exerts its immune-regulatory functions by targeting different downstream signaling pathways.