Modulation of mitogenic activity and cellular binding of basic fibroblast growth factor by basic proteins.
Polycationic molecules were studied either for their ability to displace the binding of basic fibroblast growth factor (bFGF) to high- and low-affinity membrane interaction sites and/or to modulate bFGF-induced proliferation of fibroblasts. Heparin-binding polypeptides, such as polylysine, protamine, histones, and thrombin-displaced [125I]bFGF bound to bovine brain membrane receptors. The most displacing polypeptides were those with the strongest affinity to heparin. Two of these polypeptides, protamine and polylysine, inhibited (at 5 microM) by more than 90% the mitogenic effect induced by bFGF on Chinese hamster lung fibroblast cells (CCL39). At the same dose, no effect was observed with basic proteins that do not bind to heparin, such as cytochrome C and lysozyme. An interesting observation was that protamine at 1 microM potentiated by 1.5-fold the mitogenic activity of bFGF, while it acted as an inhibitor at higher concentration.
Dauchel
M C
MC
Laboratoire de Biotechnologie des Cellules Eucaryotes, Université Paris XII, Créteil, France.
Courty
J
J
Mereau
A
A
Barritault
D
D
D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D019763:Heparin Lyase; D008934:Mitogens / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011869:Radioligand Assay
D008934:Mitogens; D011479:Protamines; D011506:Proteins; D005346:Fibroblast Growth Factors; D004247:DNA; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase