Mediators of angiogenesis: the biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions.
The interactions of basic fibroblast growth factor (bFGF) with heparin-like molecules appear to be biologically significant. Heparin and heparan sulfate protect bFGF from inactivation by heat, extreme pH and protease degradation. At the cellular level, bFGF binds to heparan sulfate on the cell surface. Cell surface heparan sulfate proteoglycans (HSPG) constitute relatively low affinity binding sites for bFGF. Furthermore, binding of bFGF to cell surface HSPG is necessary for its binding to high affinity FGF receptors and for its mitogenic activity. Thus, bFGF activity requires a dual receptor system composed of a classical protein-type tyrosine kinase receptor and a lower affinity glycosaminoglycan-type receptor. In addition, bFGF is bound to HSPG in the extracellular matrix (ECM). It has been suggested that bFGF may be sequestered in ECM as part of a stable insoluble FGF-HSPG complex from which it is released by specific enzymatic mechanisms when needed for mitogenic activity.
Klagsbrun
M
M
Department of Surgery, Children's Hospital, Boston, MA 02115.
D000818:Animals; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D006133:Growth Substances / Q000378:metabolism; D006493:Heparin / Q000378:metabolism / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology
D016222:Fibroblast Growth Factor 2; D006133:Growth Substances; D006493:Heparin; D006497:Heparan Sulfate; D011509:Proteoglycans; D011956:Receptors, Cell Surface