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Specific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor
In a previous study, we showed that heparitinase releases a 14-saccharide sequence (Oligo-H) from heparan sulfate (HS) with the structure delta GlcUA beta 1,4GlcNSO3-alpha 1,4[IdceA(2S)alpha 1,4GlcNSO3]5 alpha 1,4IdceA alpha 1,4GlcNAc (where IdceA(2S) represents iduronic acid 2-sulfate), which binds...
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Published in: | The Journal of biological chemistry 1994-01, Vol.269 (2), p.931-935 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | In a previous study, we showed that heparitinase releases a 14-saccharide sequence (Oligo-H) from heparan sulfate (HS) with
the structure delta GlcUA beta 1,4GlcNSO3-alpha 1,4[IdceA(2S)alpha 1,4GlcNSO3]5 alpha 1,4IdceA alpha 1,4GlcNAc (where IdceA(2S)
represents iduronic acid 2-sulfate), which binds to basic fibroblast growth factor (bFGF) with high affinity (Turnbull, J.
E., Fernig, D., Ke, Y., Wilkinson, M. C. & Gallagher, J. T. (1992) J. Biol. Chem. 267, 10337-10341). This paper describes
further work on the binding properties of HS saccharides and their capacity to mediate bFGF activity in a mitogenesis assay
in which responsiveness is dependent on the addition of HS or heparin. Saccharides prepared by heparinase or nitrous acid
digestion and heparitinase-resistant fragments five disaccharide units (degree of polymerization (dp) = 10) or less in size
were unable to activate bFGF. However, heparitinase-resistant saccharides of dp12-16 were active in the assay; the dp14 and
dp16 fractions were equivalent in activity to heparin and more active than the parent HS. Saccharides of the same size and
basic structure as the active fractions (> or = dp12) bound to bFGF with high relative affinity. Active saccharides were composed
mainly of N-sulfated disaccharides, the predominant unit being IdceA(2S)-GlcNSO3. This was enriched at least 5-fold in the
active saccharides by comparison with the original HS. In addition, the dp12 and dp14 active fractions had a notably low content
of trisulfated disaccharides (IdceA(2S)-GlcNSO3(6S)) (where GlcNSO3(6S) represents N-sulfated glucosamine 6-sulfate), which
are the major repeat units of heparin. The data show that sequences similar in size and basic structure to Oligo-H can mediate
the mitogenic activity of bFGF. Overall, the results provide further evidence that specific HS sequences are generated biosynthetically
in order to fulfill particular biological functions such as activation of bFGF. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(17)42201-0 |