Physicochemical Activation of Recombinant Latent Transforming Growth Factor-beta's 1, 2, and 3

Abstract

Native and recombinant forms of transforming growth factor-beta 1 (TGF-β1) are synthesized predominantly as biologically latent complexes. Physicochemical analysis demonstrates that the more recently described TGF-β2 and TGF-β3 are also latent, and reveals a common series of sharply defined parameters for activation. Human recombinant latent TGF-βs 1 and 2 show identical profiles of activation by acid and base; the transition from latency occurs between pH 4.1 and 3.1, and between pH 11.0 and 11.9. The profile for chicken recombinant latent TGF-β3 is slightly shifted with activation between pH 3.1 and 2.5, and between pH 10.0 and 12.3. Thermal activation of native and recombinant latent TGF-β1 occurs over the temperature ranges of 75–100°C and 65–100°C, respectively, with complete activation after 5 min at 80°C. Temperatures above 90°C result in thermal denatura-tion of TGF-β1 itself. Recombinant latent TGF-βs 2 and 3 are also activated over this temperature range; however, maximum activation occurs at 100°C. These results suggest common elements in latent complex structure despite differences between the TGF-β subtypes in pro-region primary sequence.