Latency, activation, and binding proteins of TGF-beta

The TGF-beta superfamily of growth factors consists of an increasing number of different polypeptide modulators of cell growth, differentiation, and m orphogenesis. Three mammalian isoforms have been molecularly cloned. Numero us ways to regulate the expression of the TGF-beta genes have been identifi ed. TGF-betas are, for example, subject to regulation by retinoids, steroid hormones, and vitamin D. A characteristic feature in the biology of TGF-be tas is that they are usually secreted from cells in latent forms. The large latent complex consists of the small latent complex (TGF-beta and its prop eptide) and a high molecular weight protease resistant binding protein, lat ent TGF-beta binding protein (LTBP). LTBPs are required for the proper fold ing and secretion of TGF-beta. TGF-beta is not just secreted from cultured cells but is deposited via LTBPs to the pericellular space, namely to the e xtracellular matrix. Release of these complexes and activation by proteases is under tight regulation and provides a means to rapidly increase local c oncentrations of TGF-beta. Biological events, where enhanced or focal prote olysis and activation of latent TGF-beta takes place, include cell invasion , tissue remodeling, and wound healing. Microsc. Res. Tech. 52: 354-362, 20 01. (C) 2001 Wiley-Liss, Inc.