The role of the death-domain kinase RIP in tumour-necrosis-factor-induced activation of mitogen-activated protein kinases
The role of the death-domain kinase RIP in tumour-necrosis-factor-induced activation of mitogen-activated protein kinases
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DOI：
10.1038/sj.embor.embor854
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发表时间：
2003-06-01
期刊：
影响因子：
7.7
通讯作者：
Liu, ZG
中科院分区：
文献类型：
--
作者：
Devin, A;Lin, Y;Liu, ZG
死亡域激酶RIP（受体相互作用蛋白）是肿瘤坏死因子（TNF）信号传导的重要效应子，对TNF诱导的核因子-κ B活化至关重要。然而，RIP在TNF诱导的丝裂原活化蛋白激酶（MAPK）活化中的功能尚未得到充分研究。在这份报告中，使用RIP空（RIP（-/-））小鼠成纤维细胞，我们调查是否RIP是必需的TNF诱导激活的MAPKs细胞外信号相关激酶（ERK），p38和c-Jun氨基末端激酶（JNK）。我们发现TNF诱导的ERK、p38和JNK的激活在Rip（-/-）细胞中减少。这些激酶被白细胞介素-1激活在Rip（-/-）细胞中是正常的。更重要的是，我们发现RIP的激酶活性是ERK激活所必需的。
The death-domain kinase RIP (receptor-interacting protein) is an important effector of tumour necrosis factor (TNF) signalling and is essential for TNF-induced nuclear factor-kappaB activation. However, the function of RIP in the TNF-induced activation of mitogen-activated protein kinases (MAPKs) has not been fully investigated. In this report, using Rip null (Rip(-/-)) mouse fibroblast cells, we investigated whether RIP is required for TNF-induced activation of the MAPKs extracellular-signal-related kinase (ERK), p38 and c-Jun amino-terminal kinase (JNK). We found that TNF-induced activation of ERK, p38 and JNK is decreased in Rip(-/-) cells. The activation of these kinases by interleukin-1 is normal in Rip(-/-) cells. More importantly, we showed that the kinase activity of RIP is needed for ERK activation.