Massagué J, Andres J, Attisano L, Cheifetz S, López-Casillas F, Ohtsuki M, Wrana J L
Howard Hughes Medical Institute, Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
Mol Reprod Dev. 1992 Jun;32(2):99-104. doi: 10.1002/mrd.1080320204.
The nature and role of cell surface proteins that bind members of the TGF-beta family has been investigated. TGF-beta, activins, and BMPs each bind to receptors of 55 kDa (type I) and 70 kDa (type II). In the TGF-beta system, these receptors are implicated in the mediation of multiple responses. A member of the type II receptor family has been cloned that encodes four alternatively spliced versions of a transmembrane serine/threonin kinase receptor related to the recently cloned mouse activin receptor and C-elegans daf-1 gene. Inhibitors of serine/threonine kinase activity block transcriptional and growth inhibitory responses to TGF-beta. In addition to the signaling receptors, many cell types express the TGF-beta binding proteoglycan betaglycan. Betaglycan has been purified, molecularly cloned, and shown to bind TGF-beta via its core protein and basic fibroblast growth factor via its heparan sulfate chains. In addition to receptors I and II and betaglycan, some cells express a newly identified set of membrane proteins that specifically bind either TGF-beta 1 or TGF-beta 2. Three of the four isoform-restricted binding proteins are bound to the membrane via phospholipid anchors. Like betaglycan, these proteins might function to regulate the interaction between TGF-beta and their target cells.
对结合转化生长因子-β（TGF-β）家族成员的细胞表面蛋白的性质和作用进行了研究。TGF-β、激活素和骨形态发生蛋白（BMP）均与55 kDa（I型）和70 kDa（II型）的受体结合。在TGF-β系统中，这些受体参与多种反应的介导。已克隆出II型受体家族的一个成员，它编码与最近克隆的小鼠激活素受体和秀丽隐杆线虫daf-1基因相关的跨膜丝氨酸/苏氨酸激酶受体的四种可变剪接形式。丝氨酸/苏氨酸激酶活性抑制剂可阻断对TGF-β的转录和生长抑制反应。除了信号受体外，许多细胞类型还表达TGF-β结合蛋白聚糖β-聚糖。β-聚糖已被纯化、分子克隆，并显示通过其核心蛋白结合TGF-β，通过其硫酸乙酰肝素链结合碱性成纤维细胞生长因子。除了I型和II型受体以及β-聚糖外，一些细胞还表达一组新鉴定的膜蛋白，它们特异性结合TGF-β1或TGF-β2。四种亚型限制性结合蛋白中的三种通过磷脂锚定与膜结合。与β-聚糖一样，这些蛋白可能起到调节TGF-β与其靶细胞之间相互作用的作用。
