TNF-Dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex
TNF-Dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex
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DOI：
10.1016/s1074-7613(00)80252-6
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发表时间：
1996-04-01
期刊：
影响因子：
32.4
通讯作者：
Goeddel, DV
中科院分区：
文献类型：
--
作者：
Hsu, HL;Huang, JN;Goeddel, DV
肿瘤坏死因子（TNF）受体-1（TNFR 1）的死亡结构域通过其与死亡结构域蛋白TRADD的相互作用触发导致细胞凋亡和NF-κ B活化的不同信号传导途径。在这里，我们发现TRADD与RIP强烈相互作用，RIP是另一种死亡结构域蛋白，以前被证明与Fas抗原相关。我们还表明，RIP是一种丝氨酸-苏氨酸激酶，在TNF依赖性过程中由TRADD招募至TNFR 1。完整RIP蛋白的过表达诱导NF-κ B活化和凋亡。然而，RIP的死亡结构域的表达诱导凋亡，但有效地抑制TNF对NF-κ B的激活。这些结果表明RIP的不同结构域参与了导致细胞凋亡和NF-κ B活化的TNF信号级联。
The death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD. Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen. We also show that RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process. Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis. However, expression of the death domain of RIP induces apoptosis, but potently inhibits NF-kappa B activation by TNF. These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation.