A Reaction-Diffusion Model of Basic Fibroblast Growth Factor Interactions with Cell Surface Receptors

2004 ◽  
Vol 32 (5) ◽  
pp. 645-663 ◽  
Author(s):  
Renee J. Filion ◽  
Aleksander S. Popel
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Diffusion Model ◽  
Basic Fibroblast Growth Factor ◽  
Reaction Diffusion ◽  
Fibroblast Growth ◽  
Surface Receptors ◽  
Reaction Diffusion Model ◽  
Factor Interactions

Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells

1992 ◽  
Vol 12 (1) ◽  
pp. 240-247
Author(s):  
D M Ornitz ◽  
A Yayon ◽  
J G Flanagan ◽  
C M Svahn ◽  
E Levi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Receptor Binding ◽  
Receptor Activation ◽  
Soluble Form ◽  
Placental Alkaline Phosphatase ◽  
Fibroblast Growth ◽  
Fgf Receptor

Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF-receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation.

scholarly journals Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells.

1992 ◽  
Vol 12 (1) ◽  
pp. 240-247 ◽  
Author(s):  
D M Ornitz ◽  
A Yayon ◽  
J G Flanagan ◽  
C M Svahn ◽  
E Levi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Receptor Binding ◽  
Receptor Activation ◽  
Soluble Form ◽  
Placental Alkaline Phosphatase ◽  
Fibroblast Growth ◽  
Fgf Receptor

Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF-receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation.

Basic fibroblast growth factor: an extracellular mechanotransducer in articular cartilage?

2006 ◽  
Vol 34 (3) ◽  
pp. 456-457 ◽  
Author(s):  
T. Vincent ◽  
J. Saklatvala
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Articular Chondrocytes ◽  
Heparan Sulphate ◽  
Mechanical Stimuli ◽  
Fibroblast Growth ◽  
Extracellular Signal

Mechanical stimuli are important signals in articular cartilage, but what mediates them is unknown. We have shown that extracellular-signal-regulated kinase was activated on cutting and loading articular cartilage, and deduced that this was due to the release of bFGF (basic fibroblast growth factor) from the tissue. bFGF was shown to be extracellular, and by immunohistochemistry, was present in the pericellular matrix of articular chondrocytes attached to the heparan sulphate proteoglycan perlecan. We propose a novel mechanotransduction model, whereby pericellular bFGF, a short distance from the cell surface, becomes available to the cell surface tyrosine kinase receptors when articular cartilage is loaded.

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