Specific cleavage of diphtheria toxin by human urokinase.
Diphtheria toxin must undergo a specific cleavage reaction and subsequent reduction to express the enzymatic ADP-ribosyltransferase activity that is responsible for its toxicity. In an effort to identify potential cellular enzymes that might be involved in this process we have found that a human urinary plasminogen activator, urokinase, is capable of specifically cleaving diphtheria toxin to yield an enzymatically active A fragment (more homogeneous than that produced by trypsin cleavage) and a B fragment (with an identical amino-terminal sequence to that produced by trypsin cleavage). The results raise the possibility that urokinase or urokinase-like enzymes play a role in diphtheria toxin-mediated intoxication.
Cieplak
W
W
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Hasemann
C
C
Eidels
L
L
D000595:Amino Acid Sequence; D004167:Diphtheria Toxin / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013379:Substrate Specificity; D014357:Trypsin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D004167:Diphtheria Toxin; D010446:Peptide Fragments; D011065:Poly(ADP-ribose) Polymerases; D014357:Trypsin; D014568:Urokinase-Type Plasminogen Activator