Differential structural requirements of heparin and heparan sulfate proteoglycans that promote binding of basic fibroblast growth factor to its receptor
Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). The capacity of various species of heparin and heparan sulfate (HS) to promote bFGF receptor binding was investigated using both Chinese hamster ovary mutant cell...
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Published in | The Journal of biological chemistry Vol. 269; no. 1; pp. 114 - 121 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
07.01.1994
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Subjects | |
Online Access | Get full text |
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Summary: | Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth
factor (bFGF). The capacity of various species of heparin and heparan sulfate (HS) to promote bFGF receptor binding was investigated
using both Chinese hamster ovary mutant cells deficient in cell surface HSPG and a soluble bFGF receptor-alkaline phosphatase
fusion protein. Highly sulfated oligosaccharides were more effective than medium and low sulfate fractions of the same size
oligosaccharide. O-Sulfation in heparin was found to be critical for its capacity to promote binding of bFGF to its receptors.
The highest level of bFGF-receptor binding was achieved in the presence of over-sulfated heparin fragments (% sulfur > 14)
regardless of whether the N-position was sulfated or acetylated. Unlike receptor binding of bFGF which requires oligosaccharides
containing at least 8-10 sugar units, displacement of heparin- or HS-bound bFGF was obtained by oligosaccharides containing
as little as four sugar units and by an N-sulfated, O-desulfated heparin fragment (% sulfur = 5.3). A preparation of total
cell surface-derived HS induced bFGF receptor binding. A preliminary survey of several defined and affinity purified species
of cell surface HSPG, including syndecan, fibroglycan, and glypican failed to identify natural HSPG that promote high affinity
receptor binding of bFGF. A similar lack of activity was observed with species of HS isolated from bovine arterial tissue
and characterized for their effect on vascular smooth muscle cell proliferation. Moreover, most of these species of HS inhibited
in a dose-dependent manner the restoration of bFGF-receptor binding induced by heparin or by total HSPG. These results suggest
the involvement of defined heparin-like oligosaccharide sequences and unique species of cell surface and extracellular matrix
HS in the regulation of bFGF receptor binding and biological activity. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(17)42321-0 |