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Modulation of mitogenic activity and cellular binding of basic fibroblast growth factor by basic proteins.
M C Dauchel1, J Courty, A Mereau
1Laboratoire de Biotechnologie des Cellules Eucaryotes, Université Paris XII, Créteil, France.
Journal of Cellular Biochemistry
|April 1, 1989
Summary
Polycationic molecules, like polylysine and protamine, can block basic fibroblast growth factor (bFGF) from binding to cell membranes. These molecules also inhibit bFGF-driven fibroblast proliferation, with varying effects at different concentrations.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Basic fibroblast growth factor (bFGF) plays a crucial role in cell proliferation and tissue repair.
- Understanding the regulation of bFGF binding to cell surface receptors is key to controlling its biological effects.
- Polycationic molecules, particularly heparin-binding proteins, are known to interact with growth factors.
Purpose of the Study:
- To investigate the ability of polycationic molecules to displace bFGF from membrane binding sites.
- To determine how these molecules modulate bFGF-induced fibroblast proliferation.
- To explore the relationship between heparin-binding affinity and inhibitory effects.
Main Methods:
- Studied the displacement of radiolabeled bFGF from bovine brain membrane receptors by various polycationic molecules.
- Assessed the mitogenic effect of bFGF on Chinese hamster lung fibroblast cells (CCL39) in the presence of different polycations.
- Compared the effects of heparin-binding versus non-heparin-binding basic proteins.
Main Results:
- Heparin-binding polypeptides, including polylysine, protamine, histones, and thrombin, effectively displaced bFGF from membrane receptors.
- Polyamines with higher heparin affinity showed stronger bFGF displacement.
- Protamine and polylysine significantly inhibited bFGF-induced fibroblast proliferation (>90% at 5 microM).
- Non-heparin-binding proteins (cytochrome C, lysozyme) did not affect bFGF binding or proliferation.
- Protamine exhibited a dual effect: potentiation of mitogenic activity at 1 microM and inhibition at higher concentrations.
Conclusions:
- Heparin-binding polycationic molecules can effectively compete with bFGF for membrane receptor binding.
- These molecules serve as potent inhibitors of bFGF-mediated fibroblast proliferation.
- The concentration-dependent activity of molecules like protamine highlights the complex regulation of growth factor signaling by polycations.