Potential Mechanisms for the Regulation of Growth Factor Binding by Heparin

✍ Scribed by KIMBERLY E FORSTEN; MICHAEL FANNON; MATTHEW A NUGENT

• Publisher: Elsevier Science
• Year: 2000
• Tongue: English
• Weight: 290 KB
• Volume: 205
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.2000.2064

✦ Synopsis

Heparin and heparan sulfate proteoglycans (HSPG) bind many soluble growth factors and this binding is now recognized as an important mechanism for modulation of cell activity. Fibroblast growth factor-2 (FGF-2) is one of the best characterized of the heparin-binding growth factors and it has been shown experimentally that heparin regulation of FGF-2 activity is dependent on the level of cell HSPG and the concentration of heparin. In this paper, we explore, using mathematical modeling, proposed mechanisms for heparin regulation and determine how they impact FGF receptor binding. We demonstrate that the experimentally observed receptor binding phenomena can be reproduced if cells (1) express heparin-binding cell surface molecules and if either (2) these heparin binding sites are FGFR and bind heparin and FGF-2-heparin complexes or (3) are surface molecules able to bind FGF-2 and couple with FGF-2 receptors to form high-a$nity FGF-2-bound surface complexes. The ability of heparin to directly interact with the FGFR and bind FGF-2 in the absence of this coupling function was not su$cient to explain heparin activity. These "ndings have implications with regard to regulation of heparin-binding growth factors and could help guide the development of highly speci"c growth regulatory molecules through speci"c regulation by heparin and HSPG.