Characterization of fibroblast growth factor 1 binding heparan sulfate domain.
Fibroblast growth factors FGF-1 and FGF-2 mediate their biological effects via heparan sulfate-dependent interactions with cell surface FGF receptors. While the specific heparan sulfate domain binding to FGF-2 has been elucidated in some detail, limited information has been available concerning heparan sulfate structures involved in the recognition of FGF-1. In the current study we present evidence that the minimal FGF-1 binding heparan sulfate sequence comprises 5-7 monosaccharide units and contains a critical trisulfated IdoA(2-OSO3)-GlcNSO3(6-OSO3) disaccharide unit. N-Sulfated heparan sulfate decasaccharides depleted of FGF-1 binding domains showed dose-dependent and saturable binding to FGF-2. These data indicate that the FGF-1 binding domain is distinct from the minimal FGF-2 binding site, previously shown to contain an IdoA(2-OSO3) residue but no 6-O-sulfate groups. We further show that the FGF-1 binding heparan sulfate domain is expressed in human aorta heparan sulfate in an age-related manner in contrast to the constitutively expressed FGF-2 binding domain. Reduction of heparan sulfate O-sulfation by chlorate treatment of cells selectively impedes binding to FGF-1. The present data implicate the 6-O-sulfation of IdoA(2-OSO3)-GlcNSO3 units in cellular heparan sulfate in the control of the biological activity of FGF-1.
Kreuger
J
J
Department of Medical Biochemistry and Microbiology, Uppsala University, S-75123, Uppsala, Sweden.
Prydz
K
K
Pettersson
R F
RF
Lindahl
U
U
Salmivirta
M
M
D000818:Animals; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002417:Cattle; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine
D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D011994:Recombinant Proteins