D. Aviezer et al., Heparin differentially regulates the interaction of fibroblast growth factor-4 with FGF receptors 1 and 2, BIOC BIOP R, 263(3), 1999, pp. 621-626
Citations number
37
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Fibroblast growth factor-4 (FGF4), like other FGFs, shares a high affinity
for the anionic glycosaminoglycans heparin and heparan sulfate (HS), which
in turn enhance FG;F-receptor (FGFR) binding and activation. Here we demons
trate using a cell free system that, at low concentrations of heparin, FGF4
binds only to FGFR-2, while much higher heparin levels are required for bi
nding to FGFR-1. Chemical crosslinking of radiolabeled FGF I to the soluble
FGF receptors confirms the preferential formation of FGF4-FGFR-2 complexes
under restricted heparin availability, with maximal ligand-receptor intera
ctions at almost 20-fold lower heparin concentrations then those required f
or the affinity labeling of FGFR-1. In accordance, HS-deficient cells expre
ssing FGFR-2 proliferate in response to FGF4 at extremely low exogenous hep
arin concentrations, while FGFR-1 expressing cells are completely unrespons
ive under the same conditions. We suggest that FGFR-2 is the preferred rece
ptor for FGF4 under restricted HS conditions and that the bioavailability o
f structurally distinct HS motifs may differentially control receptor speci
ficity of FGF4 in vivo. (C) 1999 Academic Press.