Not all perlecans are created equal: interactions with fibroblast growth factor (FGF) 2 and FGF receptors.
Affiliation
Commonwealth Scientific Industrial Research Organization (CSIRO) Molecular Science, North Ryde 2113, Australia.Issue Date
2002-04-26
Metadata
Show full item recordAbstract
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.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 ChemistryDOI
10.1074/jbc.M111826200PubMed ID
11847221Type
ArticleLanguage
enISSN
0021-9258ae974a485f413a2113503eed53cd6c53
10.1074/jbc.M111826200
Scopus Count
Collections
Related articles
- Electrophoretic, biosensor, and bioactivity analyses of perlecans of different cellular origins.
- Authors: Knox S, Melrose J, Whitelock J
- Issue date: 2001 Dec
- Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors.
- Authors: Smith SM, West LA, Govindraj P, Zhang X, Ornitz DM, Hassell JR
- Issue date: 2007 Apr
- Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase.
- Authors: Kan M, Wu X, Wang F, McKeehan WL
- Issue date: 1999 May 28
- Ablation of Perlecan Domain 1 Heparan Sulfate Reduces Progressive Cartilage Degradation, Synovitis, and Osteophyte Size in a Preclinical Model of Posttraumatic Osteoarthritis.
- Authors: Shu CC, Jackson MT, Smith MM, Smith SM, Penm S, Lord MS, Whitelock JM, Little CB, Melrose J
- Issue date: 2016 Apr
- Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition.
- Authors: Allen BL, Filla MS, Rapraeger AC
- Issue date: 2001 Nov 26