FUNCTION OF THE INTERFERON-INDUCED PROTEIN KINASE DAI

描述（改编自研究者摘要）：蛋白激酶 在高等生物的细胞调节回路中起关键作用。 蛋白激酶DAI，即双链RNA（dsRNA）被激活， 存在翻译抑制剂（也称为P1或p68激酶 在大多数细胞中处于基础水平。 DAI的合成是由 干扰素和激酶在一个过程中被dsRNA激活， 自磷酸化 DAI磷酸化起始因子eIF-2 （真核起始因子2），从而削弱启动 蛋白质合成;它也磷酸化其他底物，至少在 体外它在干扰素诱导的抗病毒反应中的作用是很好的 成立，DAI最近被卷入恶性 转型以及其他监管过程。 本研究的目的是了解 DAI的生物学功能和生化活性 水平 为此，本申请的目的是（i）表征 DAI与其激活剂dsRNA之间的相互作用;（ii）探索 其底物的性质及其被活化的DAI磷酸化; (iii)阐明自磷酸化和激活的机制 （iv）研究DAI的生物学作用，特别是在 病毒感染和细胞转化;以及（v）确定 酶的结构的详细使用生物物理方法。 从长远 这些研究将阐明生长控制的过程， 病毒感染，并可能导致干预策略， 癌症和病毒性疾病。

DESCRIPTION (Adapted from the Investigator's Abstract):Protein kinases play key roles in the cellular regulatory circuits of higher organisms. The protein kinase DAI, the double-stranded RNA (dsRNA) activated inhibitor of translation (also known as P1 or p68 kinase), is present in most cells at a basal level. The synthesis of DAI is induced by interferon, and kinase is activated by dsRNA in a process that involves autophosphorylation. DAI phosphorylates the initiation factor elF-2 (eukaryotic initiation factor 2), thereby impairing the initiation of protein synthesis; it also phosphorylates other substrates, at least in vitro. Its role in the interferon-induced anti- viral response is well established, and DAI has recently been implicated in malignant transformation as well as other regulatory processes. The objective of the research proposed here is to understand the biological functions and biochemical activities of DAI at the molecular level. To this end, the aims of the application are (i) to characterize the interaction between DAI and its activator, dsRNA; (ii) to explore the nature of its substrates and their phosphorylation by activated DAI; (iii) to elucidate the mechanism of autophosphorylation and activation of the enzyme; (iv) to study the biological roles of DAI, especially in virus infection and cellular transformation; and (v) to determine the enzyme's structure in detail using biophysical methods. In the long term, these studies will illuminate the processes of growth control and of virus infection, and may lead to strategies for intervention in cancer and viral diseases.