Expression cloning of a diphtheria toxin receptor: identity with a heparin-binding EGF-like growth factor precursor.
A monkey cDNA (pDTS) encoding a diphtheria toxin (DT) sensitivity determinant was isolated by expression cloning in mouse L-M cells. Mouse cells are naturally resistant to DT, because they lack functional cell surface receptors for the toxin. Unlike wild-type L-M cells, pDTS-transfected mouse cells are extremely toxin sensitive and specifically bind radioiodinated DT. Intoxication of the transfected cells requires receptor-mediated endocytosis of the bound toxin. The cDNA is predicted to encode an integral membrane protein that is identical to the precursor of a heparin-binding EGF-like growth factor. The DT sensitivity protein is thus a growth factor precursor that DT exploits as a receptor.
Naglich
J G
JG
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Metherall
J E
JE
Russell
D W
DW
Eidels
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D004247:DNA / Q000235:genetics; D004167:Diphtheria Toxin / Q000378:metabolism*; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic / Q000235:genetics*; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology
D003432:Cross-Linking Reagents; D004167:Diphtheria Toxin; D006133:Growth Substances; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D006493:Heparin; D004247:DNA; D014357:Trypsin