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TGF-ß Latency: Biological Significance and Mechanisms of Activation

Department of Cell Biology and Kaplan Cancer Center and the Raymond and Beverly Sackler Foundation Laboratory, New York University Medical Center, New York, New York, USA

Key Words. Growth factor • Transforming growth factor-ß • Latent TGF-ß binding protein (LTBP ) • Extracellular matrix • Bioavailability • Proteases

Dr. Pierre-Emmanuel Gleizes, Department of Cell Biology, NYU Medical Center, 550 First Avenue, New York, NY 10016, USA.

Transforming growth factor (TGF-)ß 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-ß activation or TGF-ß formation. Although latent TGF-ß 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-ß. 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-ß formation based upon the observations with different cell systems and on recent findings on the structure of the latent TGF-ß complex.

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