The mechanism of action of transforming growth factor-beta

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.