删除SHIP或SHP-1揭示了抑制信号传递的两个不同的途径
1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
Cell
|July 25, 1997
概括
免疫抑制核心受体利用不同的酸酶,SHP-1 (含SH2的内醇酸酶1) 或SHIP (含SH2的内醇酸酶),进行信号传递. 这种选择性招募决定了B细胞受体触发的亡的结果.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞信号传递 细胞信号传递
- 分子生物学分子生物学
背景情况:
- 抑制性核心受体调节免疫受体的激活.
- 伊诺西多酸5'-酸酶 (SHIP) 和氨酸酸SHP-1是关键的信号分子.
- 它们在抑制信号通路中的特定作用尚未完全阐明.
研究的目的:
- 研究SHIP和SHP-1在免疫抑制信号传递中的必要性,相互作用和冗余性.
- 定义由这些酸酶介导的不同类别的抑制反应.
- 了解它们对B细胞受体 (BCR) 触发的亡的影响.
主要方法:
- 生成缺乏SHP-1和缺乏SHIP的B细胞系.
- 评估这些细胞系中的抑制信号传递能力.
- 对BCR触发的亡反应对受体参与的分析.
主要成果:
- 确定了两种不同的抑制反应类别,选择性地招募SHP-1或SHIP.
- Fc gammaRIIB介导的抑制信号需要SHIP,而不是SHP-1.
- 通过KIR介导的抑制信号需要SHP-1,而不是SHIP.
- SHP-1信号阻断了亡,而SHIP信号减弱了由Fc gammaRIIB启动的亲亡信号.
结论:
- SHIP和SHP-1在调解抑制性核心受体信号传递方面发挥着不同的非冗余作用.
- 这些酸酶的选择性招募决定了细胞的结果,特别是BCR触发的亡.
- 这种选择性招募提供了一个微调免疫反应的机制.
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