Regulation of the Bioavailability of TGF-β and TGF-β-Related Proteins

The bioavailability of members of the transforming growth factor beta (TGF-beta) family is controlled by a number of mechanisms. Bona fide TGF-beta is sequestered into the matrix in a latent state and must be activated before it can bind to its receptors. Here, we review the molecules and mechanisms that regulate the bioavailability of TGF-beta and compare these mechanisms with those used to regulate other TGF-beta family members. We also assess the physiological significance of various latent TGF-beta activators, as well as other extracellular modulators of TGF-beta family signaling, by examining the available in vivo data from knockout mouse models and other biological systems.