Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor.
Human MDA MB 231 cells were found to synthesize mostly the cell surface-associated precursor form of heparin-binding EGF-like growth factor (HB-EGF), a 27-kDa protein. Evidence for this form of HB-EGF included increased fluorescence intensity when cells were analyzed by flow cytometry using anti-HB-EGF antibodies, lack of HB-EGF in conditioned medium, and sensitivity to diphtheria toxin, for which HB-EGF is the receptor. Phorbol ester treatment of cells resulted, within 30 minutes, in loss of cell surface 27 kDA HB-EGF, lack of interaction with anti-HB-EGF antibodies, accumulation of active 21 kDa HB-EGF in conditioned medium, and the acquisition of diphtheria toxin resistance. It was concluded that cell surface-associated HB-EGF is the precursor of a bioactive growth factor, is biologically active as the receptor for diphtheria toxin, and is susceptible to rapid processing.
Department of Surgery, Children's Hospital, Harvard Medical School, Boston, MA 02115.
G
G
Raab
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S
Higashiyama
S
S
Hetelekidis
J A
JA
Abraham
D
D
Damm
M
M
Ono
M
M
Klagsbrun
D004167:Diphtheria Toxin / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004167:Diphtheria Toxin; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D013755:Tetradecanoylphorbol Acetate