Cytotoxic activity of a recombinant fusion protein between interleukin 4 and Pseudomonas exotoxin.
- 1 June 1989
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 86 (11) , 4215-4219
- https://doi.org/10.1073/pnas.86.11.4215
Abstract
A recombinant chimeric toxin in which the binding cell domain of Pseudomonas exotoxin (PE) was replaced by murine interleukin 4 (IL-4) was produced by Escherichia coli. This chimeric protein, IL-4-PE40, was cytotoxic to murine IL-4 receptor-bearing cell lines but had little effect on human cell lines lacking receptors capable of binding murine IL-4. A mutant form of IL-4-PE40 (termed IL-4-PE40 asp553) with very low ADP-ribosylating activity displayed mitogenic activity similar to that of IL-4 rather than cytotoxic activity. Because the cytotoxic effects of IL-4-PE40 were blocked by excess IL-4 or by neutralizing antibody to IL-4 (11B11), we conclude that the cytotoxic effect of IL-4-PE40 is specifically mediated through IL-4 receptors. IL-4-PE40 could be a useful reagent for specific elimination of cells bearing IL-4 receptors.Keywords
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