Cheifetz S, Massagué J
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
J Biol Chem. 1989 Jul 15;264(20):12025-8.
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.
III型转化生长因子-β（TGF-β）受体是一种细胞表面硫酸软骨素/硫酸乙酰肝素蛋白聚糖，它能以高亲和力和特异性结合多种形式的TGF-β。在此，我们采用遗传学方法来确定糖胺聚糖（GAG）链对于正常TGF-β受体表达的需求，以及受体蛋白聚糖核心和GAG链在TGF-β结合中所起的作用。与野生型中国仓鼠卵巢（CHO）细胞相比，GAG合成缺陷的CHO细胞在其表面表达110 - 130 kDa的III型受体蛋白聚糖核心，该核心能结合正常水平的TGF-β。CHO细胞突变体中受体核心对TGF-β1和TGF-β2的亲和力，与野生型CHO细胞或已绕过其代谢缺陷并表达野生型蛋白聚糖表型的CHO细胞突变体中存在的TGF-β受体蛋白聚糖形式的亲和力相似。III型受体中缺乏GAG链不会损害CHO细胞中I型和II型TGF-β受体的结合特性以及CHO细胞突变体对TGF-β的生长抑制反应。这些结果表明，GAG链对于III型受体在细胞表面的表达、TGF-β与受体核心的结合以及细胞对TGF-β的生长抑制反应来说是可有可无的。证据还表明，III型受体可能作为一种多功能蛋白聚糖，能够通过受体核心结合TGF-β，同时通过GAG链执行另一种尚未明确的功能。
