Miyazono K, Heldin C H
Ludwig Institute for Cancer Research, Uppsala, Sweden.
Gastroenterol Jpn. 1993 Mar;28 Suppl 4:81-5; discussion 86-7. doi: 10.1007/BF02782895.
Transforming growth factor-beta (TGF-beta) is a family of proteins that inhibit the growth of most epithelial cells, including hepatocytes. TGF-beta also has potent effects on the accumulation of extracellular matrix components. An increased TGF-beta production has been reported after hepatectomy and in some liver diseases; TGF-beta may thus play certain roles in the regulation of growth and metabolism of liver cells and in the development of fibrosis. TGF-beta consists of latent high molecular weight complexes; knowledge about the structure and function of the latent TGF-beta s, including the activation mechanisms, will be important for the understanding of the roles of TGF-beta in vivo. TGF-beta s exert their action on target cells via binding to cell surface receptors, several types of which have been described. The TGF-beta type II receptor was recently cloned and shown to have a serine/threonine (S/T) kinase domain in the cytoplasmic part; together with the type I receptor, it is thought to be most important for signal transduction. We have purified 40, 80 and 160 kDa glycoproteins from porcine uterus, that specifically bind TGF-beta. The elucidation of the structure and function of TGF-beta receptors and TGF-beta binding proteins will make it possible to understand the mechanisms of TGF-beta action, and in addition, may give us tools to regulate its activity in vivo.
转化生长因子-β(TGF-β)是一类能抑制包括肝细胞在内的大多数上皮细胞生长的蛋白质家族。TGF-β对细胞外基质成分的积累也有显著作用。据报道,肝切除术后及某些肝脏疾病中TGF-β的产生会增加;因此,TGF-β可能在肝细胞生长和代谢的调节以及纤维化的发展中发挥一定作用。TGF-β由潜在的高分子量复合物组成;了解潜在TGF-β的结构和功能,包括激活机制,对于理解TGF-β在体内的作用至关重要。TGF-β通过与细胞表面受体结合对靶细胞发挥作用,其中已描述了几种类型的受体。TGF-βⅡ型受体最近被克隆,并且在细胞质部分显示具有丝氨酸/苏氨酸(S/T)激酶结构域;与Ⅰ型受体一起,它被认为对信号转导最为重要。我们已从猪子宫中纯化出能特异性结合TGF-β的40 kDa、80 kDa和160 kDa糖蛋白。阐明TGF-β受体和TGF-β结合蛋白的结构和功能将有助于理解TGF-β的作用机制,此外,可能为我们提供在体内调节其活性的工具。