Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c.

Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development.

The Drosophila sugarless and sulfateless genes encode enzymes required for the biosynthesis of heparan sulfate glycosaminoglycans. Biochemical studies have shown that heparan sulfate glycosaminoglycans are involved in signaling by fibroblast growth factor receptors, but evidence for such a requirement in an intact organism has not been available. We now demonstrate that sugarless and sulfateles...

FGFs, heparan sulfate and FGFRs: complex interactions essential for development.

Fibroblast growth factors (FGFs) comprise a large family of developmental and physiological signaling molecules. All FGFs have a high affinity for the glycosaminoglycan heparin and for cell surface heparan sulfate proteoglycans. A large body of biochemical and cellular evidence points to a direct role for heparin/heparan sulfate in the formation of an active FGF/FGF receptor signaling complex. ...

Fibroblast growth factor FGF-1 Acidic fibroblast growth factor FGF-2 Basic fibroblast growth factor FGFR FGF tyrosine kinase receptor G-CSF Granulocyte colony-stimulating factor GF Growth factor HGF Hepatocyte growth factor HIF-1α Hypoxia inducible factor-1α HSPGs Heparan sulfate proteoglycans

A novel mechanism of sequestering fibroblast growth factor 2 by glypican in lipid rafts, allowing skeletal muscle differentiation.

Heparan sulfate proteoglycans (HSPGs) are critical modulators of growth factor activities. Skeletal muscle differentiation is strongly inhibited by fibroblast growth factor 2 (FGF-2). We have shown that HSPGs present at the plasma membrane are expressed in myoblasts and are downregulated during muscle differentiation. An exception is glypican-1, which is present throughout the myogenic process....

Heparan sulfate proteoglycans function as receptors for fibroblast growth factor-2 activation of extracellular signal-regulated kinases 1 and 2.

Fibroblast growth factor-2 (FGF2) activates the extracellular signal-regulated kinases 1 and 2 (ERK1/2) through its specific receptors. Interaction of FGF2 with cell-surface heparan sulfate proteoglycans has also been suggested to induce intracellular signals. Thus, we investigated whether FGF2 can stimulate ERK1/2 activation through heparan sulfate proteoglycans using mechanisms that do not de...