Transforming growth factor-β (TGF-β) receptor proteoglycan: Cell surface expression and ligand binding in the absence of glycosaminoglycan chains

Abstract

The type III transforming growth factor-β (TGF-β) receptor is a cell surface chondroitin/heparan sulfate proteoglycan that binds various forms of TGF-β with high affinity and specificity. Here, we have used a genetic approach to determine the requirement for glycosaminoglycan (GAG) chains for normal TGF-β receptor expression and the role that the receptor proteoglycan core and GAG chains play in TGF-β 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-β compared to wild type CHO cells. The affinity of the receptor core for TGF-β1 and TGF-β2 in CHO cell mutants is similar to that of the TGF-β 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-β receptor types I and II in CHO cells and the growth-inhibitory response of CHO cell mutants to TGF-β 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-β to the receptor core, and growth inhibitory response of the cells to TGF-β. The evidence also suggests that the type III receptor may act as a multifunctional proteoglycan able to bind TGF-β via the receptor core while performing another as yet unidentified function(s) via the GAG chains.