title: Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta.
abstract: We have analysed the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta). The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1. They showed only negligible binding to several other growth factors. Intact decorin, biglycan and fibromodulin isolated from bovine tissues competed with the fusion proteins for the TGF-beta binding. Affinity measurements suggest a two-site binding model with Kd values ranging from 1 to 20 nM for a high-affinity binding site and 50 to 200 nM for the lower-affinity binding site. The stoichiometry indicated that the high-affinity binding site was present in one of ten proteoglycan core molecules and that each molecule contained a low-affinity binding site. Tissue-derived biglycan and decorin were less effective competitors for TGF-beta binding than fibromodulin or the non-glycosylated fusion proteins; removal of the chondroitin/dermatan sulphate chains of decorin and biglycan (fibromodulin is a keratan sulphate proteoglycan) increased the activities of decorin and biglycan, suggesting that the glycosaminoglycan chains may hinder the interaction of the core proteins with TGF-beta. The fusion proteins competed for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and endothelial cells. Affinity labelling showed that the binding of TGF-beta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endoglin 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 fusion proteins. Latent recombinant TGF-beta 1 precursor bound slightly to fibromodulin and not at all to decorin and biglycan. The results show that the three decorin-type proteoglycans each bind TGF-beta isoforms and that slight differences exist in their binding properties. They may regulate TGF-beta activities by sequestering TGF-beta into extracellular matrix.
authors.affiliation: Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037.
authors.forename: A
authors.initials: A
authors.lastname: Hildebrand
authors.forename: M
authors.initials: M
authors.lastname: Romarís
authors.forename: L M
authors.initials: LM
authors.lastname: Rasmussen
authors.forename: D
authors.initials: D
authors.lastname: Heinegård
authors.forename: D R
authors.initials: DR
authors.lastname: Twardzik
authors.forename: W A
authors.initials: WA
authors.lastname: Border
authors.forename: E
authors.initials: E
authors.lastname: Ruoslahti
mesh_terms: D058578:Biglycan; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D016326:Extracellular Matrix Proteins; D000071235:Fibromodulin; D006801:Humans; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; C546878:DCN protein, human; D018076:DNA, Complementary; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D000071235:Fibromodulin