The tumor necrosis factor-related apoptosis-inducing ligand receptors TRAIL-R1 and TRAIL-R2 have distinct cross-linking requirements for initiation of apoptosis and are non-redundant in JNK activation
The tumor necrosis factor-related apoptosis-inducing ligand receptors TRAIL-R1 and TRAIL-R2 have distinct cross-linking requirements for initiation of apoptosis and are non-redundant in JNK activation
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DOI：
10.1074/jbc.m000482200
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发表时间：
2000-10-13
影响因子：
4.8
通讯作者：
Wajant, H
中科院分区：
文献类型：
--
作者：
Mühlenbeck, F;Schneider, P;Wajant, H
肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）受体TRAIL-R1和TRAIL-R2的过表达诱导培养细胞中的凋亡和NF-κ B的活化。在这项研究中，我们已经证明了两种受体使用表位标记的可溶性TRAIL（sTRAIL）或与单克隆抗体交联的sTRAIL的差异信号传导能力。有趣的是，sTRAIL仅在被激动性TRAIL-R1和TRAIL-R2特异性IgG制剂杀死的细胞系中足以诱导凋亡。此外，在这些细胞系中，白细胞介素-6分泌和NF-κ B活化由交联或非交联抗TRAIL以及两种受体特异性IgG诱导。然而，sTRAIL的交联是诱导仅对激动性抗TRAIL-R2-IgG应答的细胞系中的细胞凋亡所必需的。有趣的是，c-Jun N-末端激酶（JNK）的活化仅在响应于交联的sTRAIL或抗TRAIL-R2-IgG时观察到，甚至在两种受体都能够信号传导凋亡和MF-κ B活化的细胞系中也是如此。总之，我们的数据表明，TRAIL-R1响应于交联或非交联的sTRAIL，其信号传导NF-κ B活化和凋亡，而TRAIL-R2信号传导NF-κ B活化、凋亡和JNK活化仅响应于交联的TRAIL。
Overexpression of the tumor necrosis factor (TNF)related apoptosis-inducing ligand (TRAIL) receptors, TRAIL-Ri and TRAIL-R2, induces apoptosis and activation of NF-kappa B in cultured cells. In this study, we have demonstrated differential signaling capacities by both receptors using either epitope-tagged soluble TRAIL (sTRAIL) or sTRAIL that was cross-linked with a monoclonal antibody. Interestingly, sTRAIL was sufficient for induction of apoptosis only in cell lines that were killed by agonistic TRAIL-R1- and TRAIL-R2-specific IgG preparations. Moreover, in these cell lines interleukin-6 secretion and NF-kappa B activation were induced by crosslinked or non-cross-linked anti-TRAIL, as well as by both receptor-specific IgGs. However, cross-linking of sTRAIL was required for induction of apoptosis in cell lines that only responded to the agonistic anti-TRAIL-R2-IgG. Interestingly, activation of c-Jun N-terminal kinase (JNK) was only observed in response to either cross-linked sTRAIL or anti-TRAIL-R2-IgG even in cell lines where both receptors were capable of signaling apoptosis and MF-kappa B activation. Taken together, our data suggest that TRAIL-R1 responds to either cross-linked or non-cross-linked sTRAIL which signals NF-kappa B activation and apoptosis, whereas TRAIL-R2 signals NF-kappa B activation, apoptosis, and JNK activation only in response to crosslinked TRAIL.