Glycosaminoglycans can influence fibroblast growth factor-2 mitogenicity without significant growth factor binding.
Fibroblast growth factors are important heparin binding, mitogenic proteins. The binding site in heparin and heparan sulfate for fibroblast growth factor-2 (basic fibroblast growth factor) has been described as rich in glucosamine-2-sulfate 1-->4 linked to iduronic acid-2-sulfate. The glucosamine residue in the heparin binding site is also 6-sulfated. A new glycosaminoglycan, acharan sulfate, has been chemically modified to prepare a polysaccharide, N-sulfoacharan sulfate, consisting of glucosamine-2-sulfate 1-->4 linked to iduronic acid-2-sulfate. Acharan sulfate binds very weakly to fibroblast growth factor-2 while N-sulfoacharan sulfate binds with nearly the same affinity as heparin. Mitogenicity studies were performed using heparan sulfate-free cells stably transfected with fibroblast growth factor receptor-1. Acharan sulfate inhibits heparin's enhancement of fibroblast growth factor-2 mitogenic activity, without affecting cell viability, while N-sulfoacharan sulfate shows heparin-like activity but at a greatly reduced level. These results suggest additional mechanisms not requiring high affinity glycosaminoglycan binding to fibroblast growth factor-2 may be important in its mitogenic activity.
Wang
H
H
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Toida
T
T
Kim
Y S
YS
Capila
I
I
Hileman
R E
RE
Bernfield
M
M
Linhardt
R J
RJ
D000818:Animals; D001665:Binding Sites; D002151:Calorimetry; D019281:Dimerization; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology*; D015394:Molecular Structure; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012908:Snails / Q000737:chemistry; D013936:Thymidine / Q000378:metabolism
D006025:Glycosaminoglycans; D008934:Mitogens; D009844:Oligosaccharides; C106771:acharan sulfate; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D013936:Thymidine