Biological Functions of Latent TGF-β-Binding Proteins and Activation of TGF-β

Abstract

TGF-βs 1–3 are secreted from the cells as latent complexes composed of dimeric mature growth factors, the respective N-terminal propeptides latency-associated peptide (LAP) and one of the four latent TGF-β binding proteins (LTBPs). The non-covalently associated LAP renders each mature TGF-β latent; they cannot bind to the cell surface receptors and mediate their effects. LTBPs augment the secretion of each small latent complex and directs them to the extracellular matrix. The activation of TGF-β (release of mature TGF-β from the latent complex) is a central way to control the activity of TGF-β. The activation can be achieved by several proteinases, by the extracellular matrix (ECM) glycoprotein thrombospondin-1 and via a subset of cell surface integrins. Similarly, the association of the propeptides TGF-βs with different LTBPs, and subsequent different localization to the extracellular space, and potentially differential susceptibility to the activation events regulate the availability of each TGF-β: in an efficient and specific manner.