title: The transforming growth factor-beta receptor type III is a membrane proteoglycan. Domain structure of the receptor.
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.
mesh_terms: D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000032:analysis; D002808:Chondroitin Lyases / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D006026:Glycoside Hydrolases / Q000378:metabolism*; D011133:Polysaccharide-Lyases / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis*; D018125:Receptors, Transforming Growth Factor beta; D014357:Trypsin / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
chemical_list: D000345:Affinity Labels; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D014415:Tunicamycin; D006026:Glycoside Hydrolases; D014357:Trypsin; D002808:Chondroitin Lyases; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase