The activation of fibroblast growth factors (FGFs) by glycosaminoglycans: influence of the sulfation pattern on the biological activity of FGF-1.
Six synthetic heparin-like oligosaccharides have been used to investigate the effect of the oligosaccharide sulfation pattern on the stimulation of acidic fibroblast growth factor (FGF-1) induced mitogenesis signaling and the biological significance of FGF-1 trans dimerization in the FGF-1 activation process. It has been found that some molecules with a sulfation pattern that does not contain the internal trisaccharide motif, which has been proposed for high affinity for FGF-1, stimulate FGF-1 more efficiently than those with the structure of the regular region of heparin. In contrast to regular region oligosaccharides, in which the sulfate groups are distributed on both sides of their helical three-dimensional structures, the molecules containing this particular sulfation pattern display the sulfate groups only on one side of the helix. These results and the fact that these oligosaccharides do not promote FGF-1 dimerization according to sedimentation-equilibrium analysis, confirm the importance of negative-charge distribution in the activation process and strongly suggest that FGF dimerization is not a general and absolute requirement for biological activity.
Angulo
Jesús
J
Grupo de Carbohidratos, Instituto de Investigaciones Químicas, CSIC, Américo Vespucios s/n, Isla de la Cartuja, 41092 Sevilla, Spain.
Ojeda
Rafael
R
de Paz
José-Luis
JL
Lucas
Ricardo
R
Nieto
Pedro M
PM
Lozano
Rosa M
RM
Redondo-Horcajo
Mariano
M
Giménez-Gallego
Guillermo
G
Martín-Lomas
Manuel
M
D001711:Biotransformation / Q000187:drug effects; D002240:Carbohydrate Sequence; D002452:Cell Count; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D005343:Fibrinolytic Agents / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D008934:Mitogens / Q000138:chemical synthesis / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry*
D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D007202:Indicators and Reagents; D008934:Mitogens; D009844:Oligosaccharides; D013431:Sulfates; D016220:Fibroblast Growth Factor 1; D006493:Heparin