The death domain kinase RIP mediates the TNF-induced NF-κB signal
The death domain kinase RIP mediates the TNF-induced NF-κB signal
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DOI：
10.1016/s1074-7613(00)80535-x
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发表时间：
1998-03-01
期刊：
影响因子：
32.4
通讯作者：
Leder, P
中科院分区：
文献类型：
--
作者：
Kelliher, MA;Grimm, S;Leder, P
死亡结构域丝氨酸/苏氨酸激酶RIP与死亡受体Pas和肿瘤坏死受体1（TNFR 1）相互作用。在体外，RIP刺激凋亡、SAPK/JNK和NF-κ B活化。为了确定RIP在体内调节细胞凋亡中的生理作用，我们通过同源重组在小鼠中引入RIP无效突变。RIP缺陷小鼠在出生时表现正常，但不能茁壮成长，在淋巴和脂肪组织中显示广泛的凋亡，并在1-3天龄时死亡。与正常的胸腺抗Fas反应相反，rip（-/-）细胞对TNF α诱导的细胞死亡高度敏感。在rip（-/-）细胞中对TNF α介导的细胞死亡的敏感性伴随着转录因子NF-κ B的激活失败。
The death domain serine/threonine kinase RIP interacts with the death receptors Pas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-kappa B activation. To define the physiologic role(s) that RIP plays in regulating apoptosis in vivo, we introduced a rip null mutation in mice through homologous recombination. RIP-deficient mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose tissue and dying at 1-3 days of age. In contrast to a normal thymic anti-Fas response, rip(-/-) cells are highly sensitive to TNF alpha-induced cell death. Sensitivity to TNF alpha-mediated cell death in rip(-/-) cells is accompanied by a failure to activate the transcription factor NF-kappa B.