Evidence for involvement of protein kinase C in the cellular response to interferon alpha.
Evidence for involvement of protein kinase C in the cellular response to interferon alpha.
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DOI：
10.1073/pnas.87.22.8761
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发表时间：
1990-11
影响因子：
11.1
通讯作者：
N. Reich;L. Pfeffer
中科院分区：
文献类型：
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作者：
N. Reich;L. Pfeffer
磷脂/钙依赖性蛋白激酶（protein kinase C，PKC）参与人白细胞干扰素（human leukocyte interferon，IFN）介导的HeLa细胞信号转导。IFN处理导致与完整细胞结合的[3 H]佛波醇12，13-二丁酸酯迅速增加，表明PKC活化。此外，PKC抑制剂（H7和staurosporine）阻断IFN诱导的抗水泡性口炎病毒的抗病毒活性。PKC抑制剂还阻断IFN刺激的mRNA在HeLa细胞的细胞质中的积累，并抑制IFN刺激的基因的转录诱导。IFN刺激的基因的激活通过DNA应答元件介导，该DNA应答元件是对IFN的转录应答所必需和充分的。IFN治疗诱导特异性识别反应元件的几种DNA结合因子的出现，并且这些因子的出现被PKC抑制剂抑制。这一观察结果提供了证据表明，PKC活性参与干扰素刺激的信号转导。尽管PKC的激活似乎是对IFN的反应所需的，但单独的PKC活性激动剂并不能启动IFN刺激基因的表达。
Phospholipid/Ca2(+)-dependent protein kinase (protein kinase C; PKC) appears to be involved in the signal-transduction pathway mediated by human leukocyte interferon (IFN) in HeLa cells. IFN treatment results in a rapid increase in [3H]phorbol 12,13-dibutyrate binding to intact cells, indicating an activation of PKC. In addition, inhibitors of PKC (H7 and staurosporine) block the induction of antiviral activity by IFN against vesicular stomatitis virus. PKC inhibitors also block the accumulation of IFN-stimulated mRNAs in the cytoplasm of HeLa cells and suppress the transcriptional induction of IFN-stimulated genes. Activation of IFN-stimulated genes is mediated through a DNA response element that is necessary and sufficient for the transcriptional response to IFN. IFN treatment induces the appearance of several DNA-binding factors that specifically recognize the response element, and the appearance of these factors is suppressed by PKC inhibitors. This observation provides evidence that PKC activity is involved during IFN-stimulated signal transduction. Although activation of PKC appears to be required for the response to IFN, agonists of PKC activity alone do not turn on expression of IFN-stimulated genes.