Tyrosine Phosphorylation-dependent Suppression of a Voltage-gated K+ Channel in T Lymphocytes upon Fas Stimulation*
Tyrosine Phosphorylation-dependent Suppression of a Voltage-gated K+ Channel in T Lymphocytes upon Fas Stimulation*
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DOI：
10.1074/jbc.271.34.20465
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发表时间：
1996-08
期刊：
影响因子：
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通讯作者：
I. Szabó;E. Gulbins;H. Apfel;Xinfeng Zhang;P. Barth;A. Busch;K. Schlottmann;O. Pongs;F. Lang
中科院分区：
文献类型：
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作者：
I. Szabó;E. Gulbins;H. Apfel;Xinfeng Zhang;P. Barth;A. Busch;K. Schlottmann;O. Pongs;F. Lang
选择性细胞死亡在免疫系统的发育和表达外源抗原的靶细胞的消除中起着关键作用。大多数程序性细胞死亡是通过细胞凋亡发生的。APO-1/Fas （CD95）抗原对淋巴细胞凋亡的影响[Suda， T., and Nagata， S.(1994) .中华医学杂志。Nagata， S.和Golstein， P. (1995) Science 267, 1449-1456)。我们发现Fas的激活导致Jurkat T淋巴细胞中电压依赖性n型K+通道（Kv1.3）的抑制。酪氨酸激酶已被证明在fas诱导的细胞死亡中起关键作用（Eischen, c.m., Dick, c.j., and Leibson, p.j. (1994) J. Immunol. 153, 1947-1954）。电流的抑制作用与免疫沉淀和印迹K+通道蛋白的酪氨酸磷酸化有关。我们发现，src样蛋白酪氨酸激酶抑制剂herbimycin A和突变Jurkat细胞中p56lck酪氨酸激酶的缺失消除了抗Fas抗体对通道的抑制和磷酸化，而p56lck激酶的重构部分恢复了Fas受体触发的这些作用。这些结果表明酪氨酸激酶在触发Fas受体时调节n型K+通道，这可能对细胞凋亡很重要。
Selective cell death plays a critical role in the development of the immune system and in the elimination of target cells expressing foreign antigens. Most of programmed cell death occurs by apoptosis. Apoptotic cell death of lymphocytes can be triggered by ligation of APO-1/Fas (CD95) antigen (Suda, T., and Nagata, S. (1994) J. Exp. Med. 179, 873-879; Nagata, S., and Golstein, P. (1995) Science 267, 1449-1456). We find that activation of Fas leads to the inhibition of the voltage-dependent n-type K+ channels (Kv1.3) studied by patch clamp technique in Jurkat T lymphocytes. Tyrosine kinases have been shown to be crucial in Fas-induced cell death (Eischen, C. M., Dick, C. J., and Leibson, P. J. (1994) J. Immunol. 153, 1947-1954). The inhibition of the current is correlated with the tyrosine phosphorylation of immunoprecipitated and blotted K+ channel protein. We show, that the Src-like protein-tyrosine kinase inhibitor herbimycin A and the deficiency of the p56lck tyrosine kinase in mutant Jurkat cells abolished the channel inhibition and phosphorylation by anti-Fas antibody, while reconstitution of the p56lck kinase partly restored these effects of Fas receptor triggering. These results suggest a regulation of n-type K+ channels by tyrosine kinases upon Fas receptor triggering, which might be important for apoptosis.