Glycosaminoglycans Can Influence Fibroblast Growth Factor-2 Mitogenicity Without Significant Growth Factor Binding

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Authors
Wang, H.M.
Toida, T.
Kim, Y.S.
Capila, I.
Hileman, R.E.
Bernfield, M.
Linhardt, Robert J.
Issue Date
1998-01-06
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Article
Language
ENG
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
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.
Description
Biochemical Biophysical Research Communications, 235, 369-373
Erratum 242, 248, 1997
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Full Citation
Glycosaminoglycans Can Influence Fibroblast Growth Factor-2 MitogenicityWithout Significant Growth Factor Binding, H.M. Wang, T. Toida, Y.S.Kim, I Capila, R.E. Hileman, M. Bernfield, R.J. Linhardt, BiochemicalBiophysical Research Communications, 235, 369-373, 1997. Erratum242, 248, 1997.
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0006291X
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