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转化生长因子-β的作用机制。

The mechanism of action of transforming growth factor-beta.

作者信息

Miyazono K, Heldin C H

机构信息

Ludwig Institute for Cancer Research, Uppsala, Sweden.

出版信息

Gastroenterol Jpn. 1993 Mar;28 Suppl 4:81-5; discussion 86-7. doi: 10.1007/BF02782895.

DOI:10.1007/BF02782895
PMID:8387442
Abstract

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.

摘要

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。

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本文引用的文献

1
Involvement of transforming growth factor-beta in the formation of fibrotic lesions in carcinoid heart disease.转化生长因子-β参与类癌性心脏病纤维化病变的形成。
Am J Pathol. 1993 Jan;142(1):71-8.
2
Type 1 transforming growth factor beta: amplified expression and secretion of mature and precursor polypeptides in Chinese hamster ovary cells.1型转化生长因子β:中国仓鼠卵巢细胞中成熟和前体多肽的表达及分泌增强
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Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation.
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Structure and function of epidermal growth factor-like regions in proteins.蛋白质中表皮生长因子样区域的结构与功能
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Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization.转化生长因子β1的潜在高分子量复合物。从人血小板中纯化及结构表征。
J Biol Chem. 1988 May 5;263(13):6407-15.
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A surface component on GH3 pituitary cells that recognizes transforming growth factor-beta, activin, and inhibin.
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Purification and structural analysis of a latent form of transforming growth factor-beta from rat platelets.从大鼠血小板中纯化及分析转化生长因子-β的一种潜伏形式的结构
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10
TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences.转化生长因子-β1结合蛋白:转化生长因子-β1大潜伏复合物的一个组成成分,具有多个重复序列。
Cell. 1990 Jun 15;61(6):1051-61. doi: 10.1016/0092-8674(90)90069-q.