Betaglycan has multiple binding sites for transforming growth factor-beta 1.
The transforming growth factor-beta (TGF-beta) binding site in betaglycan, the type III TGF-beta receptor, has been variously assigned to the C-terminal half and N-terminal one-third of the extracellular domain. In this study, we show that there are at least two TGF-beta-binding sites in betaglycan. Bacterially expressed fragments bg 1,2 and bg3, which represent the N-terminal two-thirds and C-terminal one-third of betaglycan extracellular domain, both competed for the binding of 125I-TGF-beta to mink lung epithelial cells. 125I-bg1,2 bound to immobilized TGF-beta with an affinity about 4-fold higher than bg3 had. Both bg3 and bg1,2 enhanced the bioactivity of TGF-beta. The whole ectodomain of betaglycan was more active than either bg3 or bg1,2 in the assays. The binding of 125I-bg3 to TGF-beta was inhibited by bg1,2 and vice versa. The binding of 125I-bg3 and 125I-bg1,2 to TGF-beta was also inhibited by the small decorin family of proteoglycans. These results indicate that there are at least two binding sites for TGF-beta in betaglycan and that these sites recognize the same or overlapping sites in TGF-beta.
Kaname
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S
Cancer Research Center, La Jolla Cancer Research Foundation, La Jolla, CA 92037, USA.
Ruoslahti
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E
D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D008907:Mink; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; C071736:betaglycan