Mechanistic insight into contextual TGF-β signaling

Transforming growth factor-β (TGF-β) controls a wide range of cellular functions by activating both SMADs and non-SMAD pathways. In different tissue or physiological environment, cellular responses to TGF-β can be diverse, even opposite. Complex regulations at the level of ligand mobilization, receptor presentation, and the network of intracellular signal transducers afford the TGF-β pathway with versatile means to induce precise cellular responses in accordance to specific contextual demands. This article summarizes recent development in how cells manage their responses to TGF-β through ligand activation, receptor abundance, as well as SMAD-dependent and SMAD-independent mechanisms.