Specific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor.

2.50
Hdl Handle:
http://hdl.handle.net/10541/96298
Title:
Specific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor.
Authors:
Walker, A; Turnbull, Jeremy E; Gallagher, John T
Abstract:
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.
Affiliation:
Cancer Research Campaign Medical Oncology Department, University of Manchester, Great Britain.
Citation:
Specific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor. 1994, 269 (2):931-5 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
14-Jan-1994
URI:
http://hdl.handle.net/10541/96298
PubMed ID:
8288646
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWalker, Aen
dc.contributor.authorTurnbull, Jeremy Een
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2010-04-12T12:35:55Z-
dc.date.available2010-04-12T12:35:55Z-
dc.date.issued1994-01-14-
dc.identifier.citationSpecific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor. 1994, 269 (2):931-5 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid8288646-
dc.identifier.urihttp://hdl.handle.net/10541/96298-
dc.description.abstractIn 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.en
dc.language.isoenen
dc.subject.mesh3T3 Cells-
dc.subject.meshAnimals-
dc.subject.meshCell Division-
dc.subject.meshChlorates-
dc.subject.meshFibroblast Growth Factor 2-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshMice-
dc.subject.meshMolecular Weight-
dc.subject.meshOligosaccharides-
dc.subject.meshPolysaccharide-Lyases-
dc.subject.meshStructure-Activity Relationship-
dc.subject.meshSwine-
dc.titleSpecific heparan sulfate saccharides mediate the activity of basic fibroblast growth factor.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Medical Oncology Department, University of Manchester, Great Britain.en
dc.identifier.journalThe Journal of Biological Chemistryen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.