Abstract
The transforming growth factor-beta (TGF-beta) receptor type III is a low abundance cell surface component that binds TGF-beta 1 and TGF-beta 2 with high affinity and specificity, and is present in many mammalian and avian cell types. Type III TGF-beta receptors affinity-labeled with 125I-TGF-beta migrate in sodium dodecyl sulfate-polyacrylamide electrophoresis gels as diffuse species of 250-350 kDa. Here we show that type III receptors deglycosylated by the action of trifluoromethanesulfonic acid yield affinity-labeled receptor cores of 110-130 kDa. This marked decrease in molecular weight is also achieved by combined treatment of type III receptors with heparitinase and chondroitinase ABC. Digestion of receptor-linked glycosaminoglycans by treatment of intact cell monolayers with heparitinase and chondroitinase does not prevent TGF-beta binding to the type III receptor core polypeptide and does not release the receptor polypeptide from the membrane. The type III TGF-beta receptor binds tightly to DEAE-Sephacel and coelutes with cellular proteoglycans at a characteristically high salt concentration. Thus, the type III TGF-beta receptor has the properties of a membrane proteoglycan that carries heparan and chondroitin sulfate glycosaminoglycan chains. The binding site for TGF-beta appears to reside in the 100-120-kDa core polypeptide of this receptor. The type III receptor is highly sensitive to cleavage by trypsin. Trypsin action releases the glycosaminoglycan-containing domain of the receptor leaving a 60-kDa membrane-associated domain that contains the cross-linked ligand. A model for the domain structure of the TGF-beta receptor type III is proposed based on these results.
Highlights
The transforming growth factor+(TGF-8) receptor type I11is alow abundance cell surface componentthat binds TGF-81 and TGF-82 with high affinity andspecificity, and is present in many mammalian and avian cell types
8 receptor hasthe propertiesof a membrane proteogly- of type I receptors correlates with inhibition of hematopoietic can that carries heparan andchondroitin sulfate gly- progenitor cell proliferation, an action induced by TGF-Pl aotcgifpolvysptecaheomiatssroiacsnrmleoectgiaonelvyopacgtrgoealeyrns.bcidcaiyTnhentha-trechiynoepstnsy.ti1panT0ei.nIh01ie-T1n1bgrr2yiedn0pcod-eskmiipnnDtagoaisarnictcoitesfoiofhrtonepihrgoehrlylerylpeeTcesaGepespnteFitsdso-ie8-rtheoeawfxdipitTphroeGhssFsiegi-oah0nne1,rdapenspokditeteThlneeGctlyaiFal-lt0mh2cauensliclnTlepGrrepFoghl-iuPeflne2aorta(itnyt1igpo1en)cs.,Telhahlaneasddshsimeuexgsipigloarenresstpspeoidrotoenttnhecaionyft leaving a 60-kDa membrane-associated domain that these effects might be mediated by activation of the type 111 contains the cross-linked ligand
The TGF-0’ are agroup of secretory disulfide-linked dimers Membrane proteins exposed on the cell surface are usually of 25 kDa that control growth and differentiation in a wide glycosylated with N - and0-linked oligosaccharide chains. variety of cell types
Summary
The proteoglycan nature of the type I11 TGF-6 receptor is unusual among cell surface istry, University of Massachusetts Medical School, 55 Lake Ave. receptors for polypeptide growth factors. The abbreviations used are: TGF-@,transforming growth factor(s)-@S; DS, sodium dodecyl sulfate; Hepes, 4-(2-hydroxyethyl)-lpiperazineethane sulfonic acid;TFMS, trifluoromethanesulfonicacid; lates the expression of various extracellular matrix components including soluble proteoglycans and the evidence for a bis-Tris, 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)-propane- role of certain membrane receptor proteoglycans in develop-.
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