Studies with pure mouse Ehrlich ascites tumor interferons alpha and beta: patterns of induction of (2'-5') (A)n synthetase and of a double-stranded RNA-dependent protein kinase in mouse cells and human cells.
The N-terminal sequences of mouse Ehrlich ascites tumor cell IFN beta (35,000-40,000 daltons) and IFN alpha (20,000 daltons) differ in 18 out of 20 positions. Furthermore, these two IFN species show little immunological cross reactivity. We treated mouse L929 cells and human HeLa S3 cells with essentially pure mouse IFN alpha or IFN beta or both at various concentrations and for various lengths of time. From the treated cells we prepared extracts and compared in these the activities of (2'-5')(A)n synthetase, an enzyme that was earlier shown to be induced by partially purified IFN preparations. The effects of treatment of mouse L929 cells with pure IFN alpha or IFN beta on (2'-5') (A)n accumulation in the cell extracts were very similar both in respect to the dependence on the length of exposure of the cells to the IFNs and on IFN concentration. Treatment with both IFN alpha and IFN beta at concentrations resulting in only partial induction of the enzyme led to an additive rather than to a synergistic effect. The maximal level of enzyme induced was the same in cells treated with high concentrations of IFN alpha or IFN beta or both. Mouse IFN alpha was as active as IFN beta in inducing a double-stranded RNA-dependent protein kinase in mouse L cells. The treatment of HeLa S3 cells with IFN beta did not affect the accumulation of (2'-5') (A)n in their extracts whereas treatment with IFN alpha boosted the accumulation though to a lesser extent than in the case of mouse L cells. These results are in line with the finding that mouse IFN alpha can, but mouse IFN beta cannot convert HeLa S3 cells into the antiviral state and also with the more pronounced homology in N-terminal sequence between mouse IFN alpha and a human (lymphoblastoid) IFN chi than between mouse IFN beta and a human IFN beta.
D015088:2',5'-Oligoadenylate Synthetase; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D002478:Cells, Cultured; D004790:Enzyme Induction; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D007372:Interferons / Q000096:biosynthesis / Q000494:pharmacology*; D007739:L Cells / Q000201:enzymology; D051379:Mice; D009374:Neoplasms, Experimental; D009713:Nucleotidyltransferases / Q000096:biosynthesis*; D011494:Protein Kinases / Q000096:biosynthesis*; D012330:RNA, Double-Stranded; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development
D012330:RNA, Double-Stranded; D007372:Interferons; D011494:Protein Kinases; D009713:Nucleotidyltransferases; D015088:2',5'-Oligoadenylate Synthetase