在55kd TNF受体内的一个新领域信号细胞死亡信号
L A Tartaglia1, T M Ayres, G H Wong
1Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.
Cell
|September 10, 1993
概括
研究人员在TNF-R1受体中发现了一种新的"死亡领域",这对信号细胞死亡至关重要. 这种域与Fas抗原保持一致,也调解抗病毒活性和氧化合成酶诱导.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 瘤坏死因子受体1 (TNF-R1) 是细胞反应的关键调解者,包括编程细胞死亡 (细胞毒性).
- TNF-R1的细胞内信号传递机制,特别是与细胞毒性和其他功能相关的机制,需要详细阐明.
- 在启动细胞毒性信号方面,Fas抗原与TNF-R1具有功能相似性,这表明信号通路得到保护.
研究的目的:
- 为了确定TNF-R1细胞内域内的特定区域,负责信号细胞毒性.
- 为了研究TNF-R1和Fas抗原之间保存的氨基酸的功能意义.
- 描述这种已识别的域在其他TNF-R1介导的信号通路中的作用,例如抗病毒活性和氧化 (NO) 合成酶诱导.
主要方法:
- 删除突变发生被用来绘制TNF-R1.1.的细胞内区域内的功能域.
- 氨酸扫描突变发生被用来评估在假定信号域内特定氨基酸的重要性.
- 进行了功能性测试,以测量细胞毒性,抗病毒活性和受体修饰后的NO合成酶诱导.
主要成果:
- 在TNF-R1的C端附近约有80个氨基酸域被确定为信号细胞毒性的关键.
- 这个域与Fas抗原的细胞内域具有微弱的同质性,保存的氨基酸对于细胞毒性信号至关重要.
- 在这个领域内的突变,被称为细胞系.
- 死亡领域是死亡领域.
- 破坏了TNF-R1信号抗病毒活性和NO合成酶诱导的能力.
- 细胞内域的膜近半部分的切除损害了NO合成酶诱导,但没有细胞毒性或抗病毒信号.
结论:
- 一个小说 一个小说
- 死亡领域是死亡领域.
- 已经在TNF-R1中确定,这对于启动编程细胞死亡至关重要.
- 这种死亡域在调解细胞毒性方面起着保留的作用,并且与Fas抗原中的类似区域相同.
- 死亡域还参与调节抗病毒反应和氧化合成酶诱导,突出显示其在细胞信号传递中的多方面的作用.
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