Expression cloning of a diphtheria toxin receptor: identity with a heparin-binding EGF-like growth factor precursor

Cell. 1992 Jun 12;69(6):1051-61. doi: 10.1016/0092-8674(92)90623-k.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Cross-Linking Reagents
  • DNA / genetics
  • Diphtheria Toxin / metabolism*
  • Gene Expression
  • Growth Substances / genetics*
  • Heparin / metabolism
  • Heparin-binding EGF-like Growth Factor
  • Hydrogen-Ion Concentration
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Receptors, Cell Surface*
  • Receptors, Cholinergic / genetics*
  • Transfection
  • Trypsin / pharmacology


  • Cross-Linking Reagents
  • Diphtheria Toxin
  • Growth Substances
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Cholinergic
  • Heparin
  • DNA
  • Trypsin

Associated data

  • GENBANK/M60278
  • GENBANK/M84120
  • GENBANK/M84163
  • GENBANK/M84182
  • GENBANK/M93012
  • GENBANK/S72766
  • GENBANK/S72767
  • GENBANK/S72768
  • GENBANK/S72769
  • GENBANK/S72771
  • GENBANK/X63098