FUNCTION OF THE INTERFERON-INDUCED PROTEIN KINASE DAI

描述（改编自研究者摘要）：蛋白激酶

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.