Mediators of angiogenesis: the biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions. 1992

M Klagsbrun
Department of Surgery, Children's Hospital, Boston, MA 02115.

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.

UI MeSH Term Description Entries
D009389 Neovascularization, Pathologic A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions. Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011509 Proteoglycans Glycoproteins which have a very high polysaccharide content. Proteoglycan,Proteoglycan Type H
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006133 Growth Substances Signal molecules that are involved in the control of cell growth and differentiation. Mitogens, Endogenous,Endogenous Mitogens
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D006497 Heparitin Sulfate A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS. Heparan Sulfate,Sulfate, Heparan,Sulfate, Heparitin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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