Cytotoxic activity of a recombinant fusion protein between interleukin 4 and Pseudomonas exotoxin.
A recombinant chimeric toxin in which the cell binding domain of Pseudomonas exotoxin (PE) was replaced by murine interleukin 4 (IL-4) was produced in 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.
Ogata
M
M
Laboratory of Molecular Biology, National Institutes of Health, Bethesda, MD 20892.
Chaudhary
V K
VK
FitzGerald
D J
DJ
Pastan
I
I
D036002:ADP Ribose Transferases; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002678:Chimera; D004926:Escherichia coli / Q000235:genetics; D005098:Exotoxins / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4; D007378:Interleukins / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000494:pharmacology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D015847:Interleukin-4; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C059989:IL-4-PE40 protein, recombinant