Petricoin E F, Ito S, Williams B L, Audet S, Stancato L F, Gamero A, Clouse K, Grimley P, Weiss A, Beeler J, Finbloom D S, Shores E W, Abraham R, Larner A C
Center for Biologics, Evaluation and Research, FDA, Bethesda, Maryland 20892, USA.
Nature. 1997 Dec 11;390(6660):629-32. doi: 10.1038/37648.
Signal transduction through both cytokine and lymphocyte antigen receptors shares some common pathways by which they initiate cellular responses, such as activation of mitogen-activated protein kinase(s). However, other signalling components appear to be uniquely coupled to each receptor. For example, the interferon receptors transduce regulatory signals through the JAK/STAT pathway, resulting in an inhibition of growth and of antiviral effects, whereas this pathway apparently plays no role in T-cell-receptor (TCR)-dependent gene expression. Conversely, signal transduction through the TCR requires the tyrosine kinases Lck and ZAP-70 and the tyrosine phosphatase CD45. Here we show that, unexpectedly, transmission of growth-inhibitory signals by interferon-alpha (IFN-alpha) in T cells requires the expression and association of CD45, Lck and ZAP-70 with the IFN-alpha-receptor signalling complex.
细胞因子和淋巴细胞抗原受体的信号转导共享一些共同途径，通过这些途径它们启动细胞反应，例如丝裂原活化蛋白激酶的激活。然而，其他信号成分似乎与每个受体独特偶联。例如，干扰素受体通过JAK/STAT途径转导调节信号，导致生长抑制和抗病毒效应，而该途径显然在T细胞受体（TCR）依赖性基因表达中不起作用。相反，通过TCR的信号转导需要酪氨酸激酶Lck和ZAP-70以及酪氨酸磷酸酶CD45。在这里，我们意外地发现，α干扰素（IFN-α）在T细胞中传递生长抑制信号需要CD45、Lck和ZAP-70与IFN-α受体信号复合物的表达和结合。
