Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species

Abstract Jobling, M. F., Mott, J. D., Finnegan, M. T., Jurukovski, V., Erickson, A. C., Walian, P. J., Taylor, S. E., Ledbetter, S., Lawrence, C. M., Rifkin, D. B. and Barcellos-Hoff, M. H. Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species. Radiat. Res. 166, 839–848 (2006). The three mammalian transforming growth factor β (TGF-β) isoforms are each secreted in a latent complex in which TGF-β homodimers are non-covalently associated with homodimers of their respective pro-peptide called the latency-associated peptide (LAP). Release of TGF-β from its LAP, called activation, is required for binding of TGF-β to cellular receptors, making extracellular activation a critical regulatory point for TGF-β bioavailability. Our previous work demonstrated that latent TGF-β1 (LTGF-β1) is efficiently activated by ionizing radiation in vivo and by reactive oxygen species (ROS) generated by Fenton chemistry in vitro. In the current study, we determined the specific ROS a...