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

1997; Elsevier BV; Volume: 235; Issue: 2 Linguagem: Inglês

10.1006/bbrc.1997.6789

1090-2104

Huiming Wang, Toshihiko Toida, Yeong Shik Kim, Ishan Capila, Ronald E. Hileman, Merton Bernfield, Robert J. Linhardt,

Glycosylation and Glycoproteins Research

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 whileN-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, whileN-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.