Interaction of Endothelial Cell Growth Factor with Heparin: Characterization by Receptor and Antibody Recognition

• Published in: Proceedings of the National Academy of Sciences - PNAS 1985-09, Vol.82 (18), p.6138-6142
• Main Authors: Schreiber, Alain B., Kenney, John, Kowalski, William J., Friesel, Robert, Mehlman, Tevie, Maciag, Thomas
• Format: Article
• Language: English
• Subjects: Antibodies; Biological and medical sciences; Cell Division - drug effects; Cell growth; Cell physiology; Cells; Cells, Cultured; Endothelial cells; Endothelial Growth Factors; Endothelium - metabolism; Epitopes; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Growth Substances - immunology; Growth Substances - metabolism; Heparin; Heparin - pharmacology; Human umbilical vein endothelial cells; Humans; Mice; Mitosis; Molecular and cellular biology; Protein Binding - drug effects; Protein Conformation - drug effects; Receptors; Receptors, Mitogen - metabolism; Receptors, Vascular Endothelial Growth Factor; Responses to growth factors, tumor promotors, other factors; Ungulates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.18.6138

Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occupancy by the ligand. Heparin interacts structurally with ECGF [Maciag, T., Mehlman, T., Friesel, R. & Schreiber, A. B. (1984) Science 225, 932-935], potentiates the mitogenic activity of the polypeptide, restores the biological activity to inactivate ECGF, enhances the affinity of the ligand to cell surface receptors, and modifies antibody recognition of ECGF. These data suggest that the association between heparin and ECGF induces a conformational change in the polypeptide that increases or stabilizes the biological activity of the mitogen.