A physical interaction between the cell death protein Fas and the tyrosine kinase p59(fynT)
A physical interaction between the cell death protein Fas and the tyrosine kinase p59(fynT)
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DOI：
10.1074/jbc.271.11.5968
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发表时间：
1996-03-15
影响因子：
4.8
通讯作者：
Bleackley, RC
中科院分区：
文献类型：
--
作者：
Atkinson, EA;Ostergaard, H;Bleackley, RC
Fas 抗原 (Apol/CD95) 是属于神经生长因子受体家族的跨膜蛋白。它在多种细胞上表达，包括活化的 T 淋巴细胞。 Fas 与其天然配体或抗 Fas 抗体的连接通常会导致细胞凋亡，使 Fas 成为下调免疫反应的重要介质。 Fas 使用的信号转导途径目前尚不清楚，尽管酪氨酸激酶活性最近已被密切关注。在这里，我们报告酪氨酸激酶 p59(fyn) 与 Fas 敏感细胞中的 Fas 发生物理关联。此外，我们还发现，与正常小鼠相比，fyn 基因敲除小鼠的活化 T 淋巴细胞在体外表现出更长的寿命和更少的细胞凋亡。此外，来自 fyn 缺陷小鼠的活化 T 淋巴细胞对抗 Fas 抗体和 Fas 配体细胞毒性 T 细胞的杀伤不太敏感。这些结果表明p59(fyn)在Fas信号转导中发挥重要作用。
The Fas antigen (Apol/CD95) is a transmembrane protein belonging to the nerve growth factor receptor family. It is expressed on a variety of cells, including activated T lymphocytes. Ligation of Fas with its natural ligand or with anti-Fas antibodies often results in the apoptotic death of the cell, making Fas an important mediator of down-regulating immune responses. The signal transduction pathways utilized by Fas are currently unknown, although tyrosine kinase activity has recently been strongly implicated. Here, we report that the tyrosine kinase p59(fyn) physically associates with Fas in Fas sensitive cells. In addition, we show that activated T lymphocytes from fyn knockout mice exhibit elevated lifespans and reduced apoptosis in vitro compared to their normal counterparts. Furthermore, activated T lymphocytes from the fyn- deficient mice are less sensitive to killing by both anti-Fas antibody and Fas-ligand cytotoxic T cells. These results suggest that p59(fyn) plays an important role in Fas signal transduction.