Fibroblast Growth Factor (FGF)-2 Mediates Cell Attachment through Interactions with Two FGF Receptor-1 Isoforms and Extracellular Matrix or Cell-Associated Heparan Sulfate Proteoglycans

2000 ◽  
Vol 276 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Christian Richard ◽  
Monireh Roghani ◽  
David Moscatelli
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Cell Attachment ◽  
Heparan Sulfate Proteoglycans ◽  
Fibroblast Growth ◽  
Fgf Receptor

scholarly journals Heparin and heparan sulfate increase the radius of diffusion and action of basic fibroblast growth factor.

1990 ◽  
Vol 111 (4) ◽  
pp. 1651-1659 ◽  
Author(s):  
R Flaumenhaft ◽  
D Moscatelli ◽  
D B Rifkin
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Morphological Changes ◽  
Fibroblast Growth ◽  
Soluble Phase ◽  
Heparan Sulfates ◽  
Sulfate Complexes

The radius of diffusion of basic FGF (bFGF) in the presence and in the absence of the glycosaminoglycans heparin and heparan sulfate was measured. Iodinated 125I-bFGF diffuses further in agarose, fibrin, and on a monolayer of bovine aortic endothelial (BAE) cells in the presence of heparin than in its absence. Heparan sulfates affected the diffusion of 125I-bFGF in a manner similar to, though less pronounced than, heparin. When applied at the center of a monolayer of BAE cells, bFGF plus heparin stimulated morphological changes at a 10-fold greater radius than bFGF alone. These results suggest that bFGF-heparin and/or heparan sulfate complexes may be more effective than bFGF alone in stimulating cells located away from the bFGF source because the bFGF-glycosaminoglycan complex partitions into the soluble phase rather than binding to insoluble glycosaminoglycans in the extracellular matrix. Thus, the complex of bFGF and glycosaminoglycan may represent one of the active forms of bFGF in vivo.

scholarly journals Homodimerization Controls the Fibroblast Growth Factor 9 Subfamily's Receptor Binding and Heparan Sulfate-Dependent Diffusion in the Extracellular Matrix

2009 ◽  
Vol 29 (17) ◽  
pp. 4663-4678 ◽  
Author(s):  
Juliya Kalinina ◽  
Sara A. Byron ◽  
Helen P. Makarenkova ◽  
Shaun K. Olsen ◽  
Anna V. Eliseenkova ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Receptor Binding ◽  
Ex Vivo ◽  
Regulatory Control ◽  
Control Mechanisms ◽  
Fibroblast Growth ◽  
Heparin Binding

ABSTRACT Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20's receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.

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