Transforming growth factor-beta (TGF-beta) receptor proteoglycan. Cell surface expression and ligand binding in the absence of glycosaminoglycan chains.
The type III transforming growth factor-beta (TGF-beta) receptor is a cell surface chondroitin/heparan sulfate proteoglycan that binds various forms of TGF-beta with high affinity and specificity. Here, we have used a genetic approach to determine the requirement for glycosaminoglycan (GAG) chains for normal TGF-beta receptor expression and the role that the receptor proteoglycan core and GAG chains play in TGF-beta binding. Chinese hamster ovary (CHO) cells defective in GAG synthesis express on their surface 110-130-kDa type III receptor proteoglycan cores that can bind normal levels of TGF-beta compared to wild type CHO cells. The affinity of the receptor core for TGF-beta 1 and TGF-beta 2 in CHO cell mutants is similar to that of the TGF-beta receptor proteoglycan forms present in wild type CHO cells or in CHO cell mutants that have been allowed to bypass their metabolic defect and express the wild type proteoglycan phenotype. The binding properties of TGF-beta receptor types I and II in CHO cells and the growth-inhibitory response of CHO cell mutants to TGF-beta are not impaired by the absence of GAG chains in the type III receptor. These results show that the GAG chains are dispensable for type III receptor expression on the cell surface, binding of TGF-beta to the receptor core, and growth inhibitory response of the cells to TGF-beta. The evidence also suggests that the type III receptor may act as a multifunctional proteoglycan able to bind TGF-beta via the receptor core while performing another as yet unidentified function(s) via the GAG chains.
Cheifetz
S
S
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
Massagué
J
J
D000116:Acetylgalactosamine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003857:Deoxyuridine / Q000037:antagonists & inhibitors; D004591:Electrophoresis, Polyacrylamide Gel; D005690:Galactose / Q000494:pharmacology; D006025:Glycosaminoglycans; D009154:Mutation; D011509:Proteoglycans / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000378:metabolism*
D006025:Glycosaminoglycans; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors; D000116:Acetylgalactosamine; D003857:Deoxyuridine; D005690:Galactose