Interaction of heparin-binding EGF-like growth factor (HB-EGF) with the epidermal growth factor receptor: modulation by heparin, heparinase, or synthetic heparin-binding HB-EGF fragments.
The binding of heparin-binding EGF-like growth factor (HB-EGF) to the epidermal growth factor (EGF) receptor of human endometrial carcinoma cells was compared to that of EGF using an 125I-EGF radioreceptor assay. The inhibitory effect of HB-EGF on 125I-EGF binding was reversed either in the presence of heparin (but not by chondroitin sulfate) or by pre-treating the cells with heparinase. These treatments did not affect the binding of EGF to its receptor. To map potential regions in the HB-EGF molecule that mediate its heparin-dependent interaction with the EGF receptor, HB-EGF peptides were synthesized that were non-homologous to EGF. Accordingly residues 20-25 and 36-41, but not residues 8-19, of HB-EGF were found to be (i) heparin-binding and (ii) modulators of HB-EGF (but not of EGF) binding to the EGF receptor.
Besner
G E
GE
Department of Surgery, Ohio State University, Columbus.
Whelton
D
D
Crissman-Combs
M A
MA
Steffen
C L
CL
Kim
G Y
GY
Brigstock
D R
DR
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D016889:Endometrial Neoplasms / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D019763:Heparin Lyase; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D011133:Polysaccharide-Lyases / Q000494:pharmacology*; D011869:Radioligand Assay; D014407:Tumor Cells, Cultured
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase