Current Biology
Volume 9, Issue 22, 18 November 1999, Pages 1343-1346
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Fibroblast growth factor receptor signalling is dictated by specific heparan sulphate saccharides

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Abstract

Signalling by fibroblast growth factors (FGFs) through FGF receptors (FGFRs) depends on the cell-surface polysaccharide heparan sulphate (HS) [1], [2]. HS has an ordered domain structure of highly diverse saccharide motifs that present unique displays of sulphate, carboxyl and hydroxyl groups [3]. These motifs interact with many proteins, particularly growth factors. HS binds both to FGFs [4], [5], [6] and FGFRs [7], and probably activates signalling by facilitating ligand-induced receptor dimerisation [8], [9].Nevertheless, the extent to which specific HS saccharide sequences play a regulatory role has not been established. By screening a library of structurally diverse HS decasaccharides in bioassays of FGF signalling mediated by three different FGFR isoforms, we found that saccharides showed specificity for both ligands and receptors; some saccharides selectively activated FGF signalling through different FGFR isoforms, others acted as negative regulators. We conclude that HS saccharides play critical roles in dictating the specificity of ligand–receptor interactions in FGFR signalling. Controlled alterations in HS structures [10] would provide a mechanism for regulation of cellular responsiveness to growth factors that bind HS.

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SE Guimond and JE Turnbull, Molecular Cell Biology Research Laboratories, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England, UK.

E-mail address for JE Turnbull (corresponding author): [email protected].