The role of heparin in the complex formation between fibroblast growth factor 2 and its high affinity receptor: comparative modelling and biochemical studies

1998 ◽  
Vol 26 (3) ◽  
pp. 545-549 ◽  
Author(s):  
L. Pellegrini ◽  
P. Commander ◽  
B. Mulloy ◽  
M. Martin-Martinez ◽  
T. L. Blundell ◽  
...  
Keyword(s):  
Growth Factor ◽  
Complex Formation ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
High Affinity ◽  
Comparative Modelling ◽  
Biochemical Studies ◽  
High Affinity Receptor ◽  
Affinity Receptor

scholarly journals Glu-96 of Basic Fibroblast Growth Factor Is Essential for High Affinity Receptor Binding

1995 ◽  
Vol 270 (37) ◽  
pp. 21869-21874 ◽  
Author(s):  
Hengyi Zhu ◽  
K. Ramnarayan ◽  
Jerry Anchin ◽  
Wendy Y. Miao ◽  
Arlene Sereno ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Receptor Binding ◽  
Fibroblast Growth ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor

scholarly journals Highly Sulfated Nonreducing End-derived Heparan Sulfate Domains Bind Fibroblast Growth Factor-2 with High Affinity and Are Enriched in Biologically Active Fractions

2011 ◽  
Vol 286 (22) ◽  
pp. 19311-19319 ◽  
Author(s):  
Hicham Naimy ◽  
Jo Ann Buczek-Thomas ◽  
Matthew A. Nugent ◽  
Nancy Leymarie ◽  
Joseph Zaia
Keyword(s):  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Ternary Complex ◽  
Biologically Active ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
High Affinity ◽  
Symmetrical Model ◽  
Asymmetrical Model

Human fibroblast growth factor-2 (FGF2) regulates cellular processes including proliferation, adhesion, motility, and angiogenesis. FGF2 exerts its biological function by binding and dimerizing its receptor (FGFR), which activates signal transduction cascades. Effective binding of FGF2 to its receptor requires the presence of heparan sulfate (HS), a linear polysaccharide with N-sulfated domains (NS) localized at the cell surface and extracellular matrix. HS acts as a platform facilitating the formation of a functional FGF-FGFR-HS ternary complex. Crystal structures of the signaling ternary complex revealed two conflicting architectures. In the asymmetrical model, two FGFs and two FGFRs bind a single HS chain. In contrast, the symmetrical model postulates that one FGF and one FGFR bind to the free end of the HS chain and dimerization require these ends to join, bringing the two half-complexes together. In this study, we screened a hexasaccharide HS library for compositions that are able to bind FGF2. The library was composed primarily of NS domains internal to the HS chain with minor presence of non-reducing end (NRE) NS. The binders were categorized into low versus high affinity binders. The low affinity fraction contained primarily hexasaccharides with low degree of sulfation that were internal to the HS chains. In contrast, the high affinity bound fraction was enriched in NRE oligosaccharides that were considerably more sulfated and had the ability to promote FGFR-mediated cell proliferation. The results suggest a role of the NRE of HS in FGF2 signaling and favor the formation of the symmetrical architecture on short NS domains.

Sign in / Sign up

Export Citation Format

Share Document