TGF-β latency: Biological significance and mechanisms of activation

Abstract

Transforming growth factor (TGF-)β is secreted as a latent complex in which the mature growth factor remains associated with its propeptide. In order to elicit a biological response, the cytokine must be released from the latent complex, a process termed latent TGF-β activation or TGF-β formation. Although latent TGF-β activation is a critical step in the regulation of its activity, little is known about the molecular mechanisms that lead to the production of active TGF-β. In this article, we present an overview of the data available on this topic, and we propose a tentative model for the mechanism of TGF-β formation based upon the observations with different cell systems and on recent findings on the structure of the latent TGF-β complex.