STRUCTURE AND FUNCTION OF FIBROBLAST GROWTH-FACTOR

Citation
Ag. Gambarini et al., STRUCTURE AND FUNCTION OF FIBROBLAST GROWTH-FACTOR, Brazilian journal of medical and biological research, 29(7), 1996, pp. 835-839
Citations number
21
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0100879X
Volume
29
Issue
7
Year of publication
1996
Pages
835 - 839
Database
ISI
SICI code
0100-879X(1996)29:7<835:SAFOFG>2.0.ZU;2-Y
Abstract
We describe some structural requirements of the fibroblast growth fact or (FGF) signaling system for the stimulation of the mitogenic respons e in terms of the design, synthesis and mitogenic activity of linear p eptides related to the human FGF-1 sequence and the structural require ments of heparin for the potentiation of the mitogenic activity of FGF -1. The best mitogenic peptide we have synthesized so far is Ac-WFVGLK KNGSSKRGPRT-NH2, that has been shown: 1) to bind to heparin-Sepharose columns with moderate affinity, requiring about 0.5 M NaCl to be elute d from the resin; 2) to be mitogenic upon BALB/c 3T3 fibroblasts in cu lture (ED(50) = 10-20 mu M) and 3)to compete with human FGF-1 for cell ular binding (ID50 = 30-50 mu M) The potentiating activity of heparin upon FGF-I has shown to be dependent on the oligosaccharide size, degr ee of sulfation and carboxylation. Apparently, these same requirements hold for the heparan sulfate molecules. Based on the reported studies , we propose some important requirements of an oligosaccharide to pote ntiate FGF-I mitogenic activity: 1) to have a minimum of twelve units, organized as disaccharides where one of the units is a uronic acid an d the second is glycosamine; 2) to have at least one iduronic acid sul fated at position 2 and 3) to have N-sulfated glycosamines, preferenti ally 6-O-sulfated. To have groups of negative charges is not enough: t hey need to be localized in a correct conformation.