A. Hildebrand et al., INTERACTION OF THE SMALL INTERSTITIAL PROTEOGLYCANS BIGLYCAN, DECORINAND FIBROMODULIN WITH TRANSFORMING GROWTH-FACTOR-BETA, Biochemical journal, 302, 1994, pp. 527-534
We have analysed the interactions of three proteoglycans of the decori
n family, decorin, biglycan and fibromodulin, with transforming growth
factor beta (TGF-beta). The proteoglycan core proteins, expressed fro
m human cDNAs as fusion proteins with Escherichia coli maltose-binding
protein, each bound TGF-beta 1. They showed only negligible binding t
o several other growth factors. Intact decorin, biglycan and fibromodu
lin isolated from bovine tissues competed with the fusion proteins for
the TGF-beta binding. Affinity measurements suggest a two-site bindin
g model with K-d values ranging from 1 to 20 nM for a high-affinity bi
nding site and 50 to 200 nM for the lower-affinity binding site. The s
toichiometry indicated that the high-affinity binding site was present
in one of ten proteoglycan core molecules and that each molecule cont
ained a low-affinity binding site. Tissue-derived biglycan and decorin
were less effective competitors for TGF-beta binding than fibromoduli
n or the non-glycosylated fusion proteins; removal of the chondroitin/
dermatan sulphate chains of decorin and biglycan (fibromodulin is a ke
ratan sulphate proteoglycan) increased the activities of decorin and b
iglycan, suggesting that the glycosaminoglycan chains may hinder the i
nteraction of the core proteins with TGF-beta. The fusion proteins com
peted for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and e
ndothelial cells. Affinity labelling showed that the binding of TGF-be
ta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endo
glin in endothelial cells was reduced, but the binding to the type-II
receptors was unaffected. TGF-beta 2 and 3 also bound to all three fus
ion proteins. Latent recombinant TGF-beta 1 precursor bound slightly t
o fibromodulin and not at all to decorin and biglycan. The results sho
w that the three decorin-type proteoglycans each bind TGF-beta isoform
s and that slight differences exist in their binding properties. They
may regulate TGF-beta activities by sequestering TGF-beta into extrace
llular matrix.