Heparan sulfate-related oligosaccharides in ternary complex formation with fibroblast growth factors 1 and 2 and their receptors.
Identifieur interne : 002D22 ( Main/Exploration ); précédent : 002D21; suivant : 002D23Heparan sulfate-related oligosaccharides in ternary complex formation with fibroblast growth factors 1 and 2 and their receptors.
Auteurs : Nadja Jastrebova [Suède] ; Maarten Vanwildemeersch ; Alan C. Rapraeger ; Guillermo Giménez-Gallego ; Ulf Lindahl ; Dorothe SpillmannSource :
- The Journal of biological chemistry [ 0021-9258 ] ; 2006.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- Animals, COS Cells, Chlorocebus aethiops, Chromatography, Fibroblast Growth Factor 1 (chemistry), Fibroblast Growth Factor 2 (chemistry), Heparitin Sulfate (chemistry), Humans, Models, Chemical, Oligosaccharides (chemistry), Protein Binding, Receptors, Fibroblast Growth Factor (chemistry), Sulfates (chemistry).
- MESH :
Abstract
Biosynthesis of heparan sulfate (HS) is strictly regulated to yield products with cell/tissue-specific composition. Interactions between HS and a variety of proteins, including growth factors and morphogens, are essential for embryonic development and for homeostasis in the adult. Fibroblast growth factors (FGFs) and their various receptors (FRs) form ternary complexes with HS, as required for receptor signaling. Libraries of HS-related, radiolabeled oligosaccharides were generated by chemo-enzymatic modification of heparin and tested for affinity to immobilized FR ectodomains in the presence of FGF1 or FGF2. Experiments were designed to enable assessment of N-sulfated 8- and 10-mers with defined numbers of iduronic acid 2-O-sulfate and glucosamine 6-O-sulfate groups. FGF1 and FGF2 were found to require similar oligosaccharides in complex formation with FR1c-3c, FGF2 affording somewhat more efficient oligosaccharide recruitment than FGF1. FR4, contrary to FR1c-3c, bound oligosaccharides at physiological ionic conditions even in the absence of FGFs, and this interaction was further promoted by FGF1 but not by FGF2. In all systems studied, the stability of FGF-oligosaccharide-FR complexes correlated with the overall level of saccharide O-sulfation rather than on the precise distribution of sulfate groups.
DOI: 10.1074/jbc.M600806200
PubMed: 16807244
Affiliations:
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Le document en format XML
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<author><name sortKey="Rapraeger, Alan C" sort="Rapraeger, Alan C" uniqKey="Rapraeger A" first="Alan C" last="Rapraeger">Alan C. Rapraeger</name>
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<author><name sortKey="Gimenez Gallego, Guillermo" sort="Gimenez Gallego, Guillermo" uniqKey="Gimenez Gallego G" first="Guillermo" last="Giménez-Gallego">Guillermo Giménez-Gallego</name>
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<series><title level="j">The Journal of biological chemistry</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>COS Cells</term>
<term>Chlorocebus aethiops</term>
<term>Chromatography</term>
<term>Fibroblast Growth Factor 1 (chemistry)</term>
<term>Fibroblast Growth Factor 2 (chemistry)</term>
<term>Heparitin Sulfate (chemistry)</term>
<term>Humans</term>
<term>Models, Chemical</term>
<term>Oligosaccharides (chemistry)</term>
<term>Protein Binding</term>
<term>Receptors, Fibroblast Growth Factor (chemistry)</term>
<term>Sulfates (chemistry)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Cellules COS</term>
<term>Chromatographie</term>
<term>Facteur de croissance fibroblastique de type 1 ()</term>
<term>Facteur de croissance fibroblastique de type 2 ()</term>
<term>Humains</term>
<term>Héparitine sulfate ()</term>
<term>Liaison aux protéines</term>
<term>Modèles chimiques</term>
<term>Oligosaccharides ()</term>
<term>Récepteur facteur croissance fibroblaste ()</term>
<term>Sulfates ()</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Fibroblast Growth Factor 1</term>
<term>Fibroblast Growth Factor 2</term>
<term>Heparitin Sulfate</term>
<term>Oligosaccharides</term>
<term>Receptors, Fibroblast Growth Factor</term>
<term>Sulfates</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>COS Cells</term>
<term>Chlorocebus aethiops</term>
<term>Chromatography</term>
<term>Humans</term>
<term>Models, Chemical</term>
<term>Protein Binding</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules COS</term>
<term>Chromatographie</term>
<term>Facteur de croissance fibroblastique de type 1</term>
<term>Facteur de croissance fibroblastique de type 2</term>
<term>Humains</term>
<term>Héparitine sulfate</term>
<term>Liaison aux protéines</term>
<term>Modèles chimiques</term>
<term>Oligosaccharides</term>
<term>Récepteur facteur croissance fibroblaste</term>
<term>Sulfates</term>
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<front><div type="abstract" xml:lang="en">Biosynthesis of heparan sulfate (HS) is strictly regulated to yield products with cell/tissue-specific composition. Interactions between HS and a variety of proteins, including growth factors and morphogens, are essential for embryonic development and for homeostasis in the adult. Fibroblast growth factors (FGFs) and their various receptors (FRs) form ternary complexes with HS, as required for receptor signaling. Libraries of HS-related, radiolabeled oligosaccharides were generated by chemo-enzymatic modification of heparin and tested for affinity to immobilized FR ectodomains in the presence of FGF1 or FGF2. Experiments were designed to enable assessment of N-sulfated 8- and 10-mers with defined numbers of iduronic acid 2-O-sulfate and glucosamine 6-O-sulfate groups. FGF1 and FGF2 were found to require similar oligosaccharides in complex formation with FR1c-3c, FGF2 affording somewhat more efficient oligosaccharide recruitment than FGF1. FR4, contrary to FR1c-3c, bound oligosaccharides at physiological ionic conditions even in the absence of FGFs, and this interaction was further promoted by FGF1 but not by FGF2. In all systems studied, the stability of FGF-oligosaccharide-FR complexes correlated with the overall level of saccharide O-sulfation rather than on the precise distribution of sulfate groups.</div>
</front>
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<li>Svealand</li>
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<settlement><li>Uppsala</li>
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<orgName><li>Université d'Uppsala</li>
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<tree><noCountry><name sortKey="Gimenez Gallego, Guillermo" sort="Gimenez Gallego, Guillermo" uniqKey="Gimenez Gallego G" first="Guillermo" last="Giménez-Gallego">Guillermo Giménez-Gallego</name>
<name sortKey="Lindahl, Ulf" sort="Lindahl, Ulf" uniqKey="Lindahl U" first="Ulf" last="Lindahl">Ulf Lindahl</name>
<name sortKey="Rapraeger, Alan C" sort="Rapraeger, Alan C" uniqKey="Rapraeger A" first="Alan C" last="Rapraeger">Alan C. Rapraeger</name>
<name sortKey="Spillmann, Dorothe" sort="Spillmann, Dorothe" uniqKey="Spillmann D" first="Dorothe" last="Spillmann">Dorothe Spillmann</name>
<name sortKey="Vanwildemeersch, Maarten" sort="Vanwildemeersch, Maarten" uniqKey="Vanwildemeersch M" first="Maarten" last="Vanwildemeersch">Maarten Vanwildemeersch</name>
</noCountry>
<country name="Suède"><region name="Svealand"><name sortKey="Jastrebova, Nadja" sort="Jastrebova, Nadja" uniqKey="Jastrebova N" first="Nadja" last="Jastrebova">Nadja Jastrebova</name>
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