SELF-ASSOCIATION OF THE DEATH DOMAINS OF THE P55 TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR AND FAS/APO1 PROMPTS SIGNALING FOR TNF AND FAS/APO1 EFFECTS
SELF-ASSOCIATION OF THE DEATH DOMAINS OF THE P55 TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR AND FAS/APO1 PROMPTS SIGNALING FOR TNF AND FAS/APO1 EFFECTS
复制标题
DOI：
10.1074/jbc.270.1.387
复制
发表时间：
1995-01-06
影响因子：
4.8
通讯作者：
WALLACH, D
中科院分区：
文献类型：
--
作者：
BOLDIN, MP;METT, IL;WALLACH, D
p55肿瘤坏死因子（TNF）受体和结构相关受体Fas/APO 1的信号传导是由受体聚集启动的。这里和其他最近的研究中提供的数据（Wallach，D.，Boldin，M.，Varfolomeev，E. E、Bigda，Y.，Camonis，H. J.和Mett，I.（1994）Cytokine 6，556; Song，H.是的，邓巴，J.D.，和Bonner，D. B。（1994）J.Biol.Chem.269，22492-22495）表明，两种受体胞内结构域内参与细胞死亡信号传导以及一些其它效应的部分区域（“死亡结构域”，特别是自缔合。我们还证明了这种关联的预期功能后果;仅增加p55 TNF受体表达，或仅表达其胞内结构域，显示触发细胞毒性信号以及白细胞介素8基因诱导，而Fas/APO 1胞内结构域的表达增强共表达p55 TNF受体的细胞毒性。这些研究结果表明，p55 TNF和Fas/APO 1受体发挥积极的作用，在自己的集群，并建议存在的细胞机制，限制这些受体的自我关联，从而防止组成性信号。
Signaling by the p55 tumor necrosis factor (TNF) receptor and by the structurally related receptor Fas/APO1 is initiated by receptor clustering. Data presented here and in other recent studies (Wallach, D., Boldin, M., Varfolomeev, E. E., Bigda, Y., Camonis, H. J. and Mett, I. (1994) Cytokine 6, 556; Song, H. Y., Dunbar, J. D., and Bonner, D. B. (1994) J. Biol. Chem. 269, 22492-22495) indicate that part of that region within the intracellular domains of the two receptors that is involved in signaling for cell, death, as well as for some other effects (the ''death domain'', specifically self-associates. We demonstrate also the expected functional consequence of this association; a mere increase in p55 TNF receptor expression, or the expression just of its intracellular domain, is shown to trigger signaling for cytotoxicity as well as for interleukin 8 gene induction, while expression of the intracellular domain of Fas/APO1 potentiates the cytotoxicity of co-expressed p55 TNF receptor. These findings indicate that the p55 TNF and Fas/APO1 receptors play active roles in their own clustering and suggest the existence of cellular mechanisms that restrict the self-association of these receptors, thus preventing constitutive signaling.