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首页> 外文期刊>Molecular and Cellular Biology >In vitro activation of a transcription factor by gamma interferon requires a membrane-associated tyrosine kinase and is mimicked by vanadate.
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In vitro activation of a transcription factor by gamma interferon requires a membrane-associated tyrosine kinase and is mimicked by vanadate.

机译：γ干扰素在体外激活转录因子需要膜相关的酪氨酸激酶，并被钒酸盐模拟。

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摘要

Gamma interferon (IFN-gamma) activates the formation of a DNA-binding protein complex (FcRF gamma) that recognizes the gamma response region (GRR) of the promoter for the human high-affinity Fc gamma receptor. In a membrane-enriched fraction prepared from human peripheral blood monocytes, IFN-gamma activation of FcRF gamma occurred within 1 min and was ATP dependent. Activation of FcRF gamma required a tyrosine kinase activity, and recognition of the GRR sequence by FcRF gamma could be abrogated by treatment with a tyrosine-specific protein phosphatase. Treatment of cells with vanadate alone resulted in the formation of FcRF gamma without the need for IFN-gamma. UV cross-linking and antibody competition experiments demonstrated that the FcRF gamma complex was composed of at least two components: the 91-kDa protein of the IFN-alpha-induced transcription complex ISGF3 and a 43-kDa component that bound directly to the GRR. Therefore, specificity for IFN-induced transcriptional activation of early response genes requires at least two events: (i) ligand-induced activation of membrane-associated protein by tyrosine phosphorylation and (ii) formation of a complex composed of an activated membrane protein(s) and a sequence-specific DNA-binding component.
机译：γ干扰素（IFN-γ）激活DNA结合蛋白复合物（FcRFγ）的形成，该复合物识别人类高亲和力Fcγ受体启动子的γ响应区域（GRR）。在由人外周血单核细胞制备的富含膜的级分中，FcRFγ的IFN-γ活化在1分钟内发生，并且是ATP依赖性的。 FcRFγ的激活需要酪氨酸激酶活性，并且通过用酪氨酸特异性蛋白磷酸酶处理可以废除FcRFγ对GRR序列的识别。单独用钒酸盐处理细胞会导致形成FcRFγ，而无需IFN-γ。紫外线交联和抗体竞争实验表明，FcRFγ复合物至少由两种成分组成：IFN-α诱导的转录复合物ISGF3的91-kDa蛋白和直接与GRR结合的43-kDa成分。因此，对IFN诱导的早期反应基因转录激活的特异性至少需要两个事件：（i）酪氨酸磷酸化配体诱导的膜相关蛋白的激活，以及（ii）由活化的膜蛋白组成的复合物的形成）和序列特异性DNA结合成分。

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