TGF-BETA, A BIOLOGICAL PEPTIDE UNDER CONT ROL - LATENT FORMS AND MECHANISMS OF ACTIVATION

Transforming growth factor-ps (TGF beta s) constitute a family of plur ipotent regulators of cell growth and differentiation. The three mamma lian isoforms of TGF beta are expressed as latent complexes that need to be converted into active forms before interacting with their ubiqui tous receptors. This review provides a summary of some recent advances in the understanding of the biochemical composition of the latent for ms of TGF beta s and of the physiological mechanisms of their activati on. Three distinct latent complexes have been characterized in the con ditioned medium of a variety of cell types: a complex between alpha(2) -macroglobulin and mature TGF beta, a non-covalent complex between the pro-region (LAP) and the mature form of TGF beta and a similar comple x containing the additional protein LTBP covalently linked to LAP. The mechanisms for activation of these latent forms in vivo are not fully characterized but may involve processes such as proteolysis and molec ular interaction with thrombospondins. Although several other factors have been implicated, the critical step controlling the biological act ivity of TGF beta appears to be the activation of the latent molecule. Modulating the level of latent TGF beta activation by die use of agon ists or antagonists of this reaction appears as a possible therapeutic approach for the treatment of auto-immune diseases, arteriosclerosis or wound healing.