通过聚类型的氨酸激酶激活T细胞
1Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Cell
|July 16, 1993
概括
细胞表面受体聚合启动免疫反应. Syk和ZAP-70激酶,但不是Src家族激酶,在受体聚类时触发T细胞激活和调动.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子信号传输的方法
背景情况:
- 免疫系统中的细胞识别依赖于细胞表面受体聚合.
- 受体相关激酶,特别是Src家族激酶,对于细胞激活至关重要.
- 这些激酶可能与抗原受体链的细胞质域相互作用.
研究的目的:
- 研究特定激酶在T细胞激活中的作用.
- 为了确定与不同激酶域的嵌合式跨膜蛋白质的聚合是否可以启动细胞信号传输.
- 为了比较T细胞中Src家族激酶与Syk和ZAP-70的信号传导能力.
主要方法:
- 构造的嵌合式跨膜蛋白具有CD16细胞外域和细胞内激酶域 (Src家族,Syk,ZAP-70).
- 在T细胞中使用抗CD16抗体诱导受体聚类.
- 监测细胞激活信号,包括调动和细胞分解效应器功能.
- 分析了氨酸酸化模式.
主要成果:
- 与Src家族激酶域相结合的嵌合体并没有启动T细胞激活.
- 用Syk或ZAP-70激酶域集群的嵌合体触发了调动.
- 单独聚合Syk嵌合体,或与Fyn和ZAP-70联合聚合,启动了细胞分解效应器功能.
- 由Syk奇梅拉聚类诱导的氨酸酸化模式模仿了T细胞受体聚合.
结论:
- 在受体聚合时,Syk和ZAP-70激酶对于启动T细胞激活信号至关重要.
- Src家族激酶不足以启动这些特定的T细胞激活事件.
- 使用Syk或ZAP-70的受体聚类可以导致下游的效应器功能,突出显示它们在免疫信号传递中的独特作用.
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