Not all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82465
Title:
Not all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors.
Authors:
Knox, Sarah; Merry, Catherine L R; Stringer, Sally E; Melrose, James; Whitelock, John
Abstract:
Human basement membrane heparan sulfate proteoglycan (HSPG) perlecan binds and activates fibroblast growth factor (FGF)-2 through its heparan sulfate (HS) chains. Here we show that perlecans immunopurified from three cellular sources possess different HS structures and subsequently different FGF-2 binding and activating capabilities. Perlecan isolated from human umbilical arterial endothelial cells (HUAEC) and a continuous endothelial cell line (C11 STH) bound similar amounts of FGF-2 either alone or complexed with FGFRalpha1-IIIc or FGFR3alpha-IIIc. Both perlecans stimulated the growth of BaF3 cell lines expressing FGFR1b/c; however, only HUAEC perlecan stimulated those cells expressing FGFR3c, suggesting that the source of perlecan confers FGF and FGFR binding specificity. Despite these differences in FGF-2 activation, the level of 2-O- and 6-O-sulfation was similar for both perlecans. Interestingly, perlecan isolated from a colon carcinoma cell line that was capable of binding FGF-2 was incapable of activating any BaF3 cell line unless the HS was removed from the protein core. The HS chains also exhibited greater bioactivity after digestion with heparinase III. Collectively, these data clearly demonstrate that the bioactivity of HS decorating a single PG is dependent on its cell source and that subtle changes in structure including secondary interactions have a profound effect on biological activity.
Affiliation:
Commonwealth Scientific Industrial Research Organization (CSIRO) Molecular Science, North Ryde 2113, Australia.
Citation:
Not all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors. 2002, 277 (17):14657-65 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
26-Apr-2002
URI:
http://hdl.handle.net/10541/82465
DOI:
10.1074/jbc.M111826200
PubMed ID:
11847221
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorKnox, Sarah-
dc.contributor.authorMerry, Catherine L R-
dc.contributor.authorStringer, Sally E-
dc.contributor.authorMelrose, James-
dc.contributor.authorWhitelock, John-
dc.date.accessioned2009-09-24T10:17:38Z-
dc.date.available2009-09-24T10:17:38Z-
dc.date.issued2002-04-26-
dc.identifier.citationNot all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors. 2002, 277 (17):14657-65 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid11847221-
dc.identifier.doi10.1074/jbc.M111826200-
dc.identifier.urihttp://hdl.handle.net/10541/82465-
dc.description.abstractHuman basement membrane heparan sulfate proteoglycan (HSPG) perlecan binds and activates fibroblast growth factor (FGF)-2 through its heparan sulfate (HS) chains. Here we show that perlecans immunopurified from three cellular sources possess different HS structures and subsequently different FGF-2 binding and activating capabilities. Perlecan isolated from human umbilical arterial endothelial cells (HUAEC) and a continuous endothelial cell line (C11 STH) bound similar amounts of FGF-2 either alone or complexed with FGFRalpha1-IIIc or FGFR3alpha-IIIc. Both perlecans stimulated the growth of BaF3 cell lines expressing FGFR1b/c; however, only HUAEC perlecan stimulated those cells expressing FGFR3c, suggesting that the source of perlecan confers FGF and FGFR binding specificity. Despite these differences in FGF-2 activation, the level of 2-O- and 6-O-sulfation was similar for both perlecans. Interestingly, perlecan isolated from a colon carcinoma cell line that was capable of binding FGF-2 was incapable of activating any BaF3 cell line unless the HS was removed from the protein core. The HS chains also exhibited greater bioactivity after digestion with heparinase III. Collectively, these data clearly demonstrate that the bioactivity of HS decorating a single PG is dependent on its cell source and that subtle changes in structure including secondary interactions have a profound effect on biological activity.en
dc.language.isoenen
dc.subject.meshCell Line-
dc.subject.meshChromatography, Gel-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshFibroblast Growth Factor 2-
dc.subject.meshHeparan Sulfate Proteoglycans-
dc.subject.meshHumans-
dc.subject.meshProtein Binding-
dc.subject.meshReceptors, Fibroblast Growth Factor-
dc.titleNot all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors.en
dc.typeArticleen
dc.contributor.departmentCommonwealth Scientific Industrial Research Organization (CSIRO) Molecular Science, North Ryde 2113, Australia.en
dc.identifier.journalThe Journal of Biological Chemistryen
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