Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells
Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells
复制标题
DOI：
10.1073/pnas.0511113103
复制
发表时间：
2006-02-28
影响因子：
11.1
通讯作者：
Gerondakis, S
中科院分区：
文献类型：
--
作者：
Banerjee, A;Gugasyan, R;Gerondakis, S
参与哺乳动物Toll样受体（TLR）激活NF-κ B和促分裂原活化蛋白激酶信号传导途径。在这里，我们建立了丝裂原活化蛋白3激酶Tp 12，其水平显着降低nfkb 1（-/-）细胞，是所需的细胞外信号调节激酶（ERK）激活骨髓衍生的巨噬细胞和B细胞刺激不同的TLR配体。尽管使用雌激素受体调节的丝裂原活化蛋白3激酶c-Raf（Raf：ER）在nfkb 1（-/-）骨髓源性巨噬细胞中挽救了TLR依赖性ERK活化，但在表达Raf：ER的nfkb 1（-/-）细胞中，CpG或LPS对IL-10的诱导仅部分恢复，这一发现与NF-κ B1通过ERK非依赖性和依赖性机制的组合调节IL-10一致。总的来说，我们的发现表明Tpl 2/MEK/ERK信号传导模块是不同造血细胞中TLR下游ERK依赖性基因表达的主调节因子。
Engaging mammalian Toll-like receptors (TLRs) activate both the NF-kappa B and mitogen-activated protein kinase signaling pathways. Here we establish that mitogen-activated protein 3 kinase Tpl2, levels of which are markedly reduced in nfkb1(-/-) cells, is required for extracellular signal-regulated kinase (ERK) activation in bone marrow-derived macrophages and B cells stimulated with diverse TLR ligands. Despite rescuing TLR-dependent ERK activation in nfkb1(-/-) bone marrow-derived macrophages by using an estrogen receptor-regulated version of the mitogen-activated protein 3 kinase, c-Raf (Raf:ER), CpG or LPS induction of IL-10 was only partially restored in nfkb1(-/-) cells expressing Raf:ER, a finding consistent with NF-kappa B1 regulating IL-10 by a combination of ERK-independent and -dependent mechanisms. Collectively, our findings indicate that the Tpl2/MEK/ERK signaling module is a master regulator of ERK-dependent gene expression downstream of TLRs in different hemopoietic cells.