Mutant with diphtheria toxin receptor and acidification function but defective in entry of toxin.
A mutant of Chinese hamster ovary cells, GE1, that is highly resistant to diphtheria toxin was isolated. The mutant contains 50% ADP-ribosylatable elongation factor 2, but its protein synthesis was not inhibited by the toxin even at concentrations above 100 micrograms/ml. 125I-labeled diphtheria toxin was associated with GE1 cells as well as with the parent cells but did not block protein synthesis of GE1 cells even when the cells were exposed to low pH in the presence or absence of NH4Cl. The infections of GE1 cells and the parent cells by vesicular stomatitis virus were similar. GE1 cells were cross-resistant to Pseudomonas aeruginosa exotoxin A and so were about 1000 times more resistant to this toxin than the parent cells. Hybrids of GE1 cells and the parent cells or mutant cells lacking a functional receptor were more sensitive to diphtheria toxin than GE1 cells. These results suggest that entry of diphtheria toxin into cells requires a cellular factor(s) in addition to those involved in receptor function and acidification of endosomes and that GE1 cells do not express this cellular factor. This character is recessive in GE1 cells.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004167:Diphtheria Toxin / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D015852:Eukaryotic Initiation Factor-2; D066257:Heparin-binding EGF-like Growth Factor; D006822:Hybrid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D009154:Mutation; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic / Q000235:genetics* / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology
D004167:Diphtheria Toxin; D015852:Eukaryotic Initiation Factor-2; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010448:Peptide Initiation Factors; D011506:Proteins; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D014118:Toxins, Biological