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dc.contributor.authorPye, David A
dc.contributor.authorVivès, Romain R
dc.contributor.authorHyde, Patricia
dc.contributor.authorGallagher, John T
dc.date.accessioned2009-11-13T15:11:51Z
dc.date.available2009-11-13T15:11:51Z
dc.date.issued2000-11
dc.identifier.citationRegulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2. 2000, 10 (11):1183-92 Glycobiologyen
dc.identifier.issn0959-6658
dc.identifier.pmid11087710
dc.identifier.doi10.1093/glycob/10.11.1183
dc.identifier.urihttp://hdl.handle.net/10541/86146
dc.description.abstractThe interaction of heparan sulfate (HS) (and the closely related molecule heparin) with FGF-1 is a requirement for enabling the growth factor to activate its cell surface tyrosine kinase receptor. However, little is known about the regulatory role of naturally occurring cell surface HS in FGF-1 activation. We have addressed this issue by utilizing a library of HS oligosaccharides, which are defined in both length and sulfate content. Mitogenic activation assays using these oligosaccharides showed that HS contained both FGF-1 activatory and inhibitory sugar sequences. Further analysis of these oligosaccharides showed a clear correlation between FGF-1 promoting activity and their 6-O-sulfate content. The results, in particular with the dodecasaccharide sequences, suggested that specific positioning of 6-O-sulfate groups may be required for the promotion of FGF-1 mitogenic activity. This may also be true for 2-O-sulfate groups though the evidence was not as conclusive. Differential activation of FGF-1 and FGF-2 was also observed and found to be mediated by both oligosaccharide length and sulfation pattern, with different specific O-sulfate positioning being implicated for the promotion of different growth factors. These results suggest that variation and tight control of the fine structure of HS may allow cells to not only control their positive/negative responses to individual FGFs but also to change specificity towards promotion of different members of the FGF family.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshCarbohydrate Sequence
dc.subject.meshCell Division
dc.subject.meshCell Line
dc.subject.meshFibroblast Growth Factor 1
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshFibroblast Growth Factors
dc.subject.meshHeparitin Sulfate
dc.subject.meshMice
dc.subject.meshMitogens
dc.subject.meshMolecular Sequence Data
dc.subject.meshOligosaccharides
dc.subject.meshStructure-Activity Relationship
dc.titleRegulation of FGF-1 mitogenic activity by heparan sulfate oligosaccharides is dependent on specific structural features: differential requirements for the modulation of FGF-1 and FGF-2.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Drug Development and CRC and University of Manchester Department of Medical Oncology, PICR, Christie Hospital, Manchester M20 4BX, UK.en
dc.identifier.journalGlycobiologyen
html.description.abstractThe interaction of heparan sulfate (HS) (and the closely related molecule heparin) with FGF-1 is a requirement for enabling the growth factor to activate its cell surface tyrosine kinase receptor. However, little is known about the regulatory role of naturally occurring cell surface HS in FGF-1 activation. We have addressed this issue by utilizing a library of HS oligosaccharides, which are defined in both length and sulfate content. Mitogenic activation assays using these oligosaccharides showed that HS contained both FGF-1 activatory and inhibitory sugar sequences. Further analysis of these oligosaccharides showed a clear correlation between FGF-1 promoting activity and their 6-O-sulfate content. The results, in particular with the dodecasaccharide sequences, suggested that specific positioning of 6-O-sulfate groups may be required for the promotion of FGF-1 mitogenic activity. This may also be true for 2-O-sulfate groups though the evidence was not as conclusive. Differential activation of FGF-1 and FGF-2 was also observed and found to be mediated by both oligosaccharide length and sulfation pattern, with different specific O-sulfate positioning being implicated for the promotion of different growth factors. These results suggest that variation and tight control of the fine structure of HS may allow cells to not only control their positive/negative responses to individual FGFs but also to change specificity towards promotion of different members of the FGF family.


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