Making sense of latent TGFβ activation

Abstract

TGFβ is secreted as part of a latent complex that is targeted to the extracellular matrix. A variety of molecules, 'TGFβ activators,' release TGFβ from its latent state. The unusual temporal discontinuity of TGFβ synthesis and action and the panoply of TGFβ effects contribute to the interest in TGF-β. However, the logical connections between TGFβ synthesis, storage and action are obscure. We consider the latent TGFβ complex as an extracellular sensor in which the TGFβ propeptide functions as the detector, latent-TGFβ-binding protein (LTBP) functions as the localizer, and TGF-β functions as the effector. Such a view provides a logical continuity for various aspects of TGFβ biology and allows us to appreciate TGFβ biology from a new perspective.