Component Hardware for Transforming Growth Factor-β Signal Transduction: TGF-β Ligands, TGF-β Receptors, and Smads

Transforming growth factor (TGF)-β is a multifunctional regulatory polypeptide that is the prototypical member of a large family of cytokines that controls many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival. The actions of TGF-β are dependent on several factors including cell type, growth conditions, and the presence of other polypeptide growth factors. The TGF-β signaling pathway has been the subject of several thousand articles that have reinforced the view of the importance of this polypeptide growth factor in normal physiology and pathology. As nearly all cells both produce and respond to TGF-β, understanding the components of the TGF-β signal transduction pathway in normal cells, including the TGF-β ligands, the TGF-β receptors, and the regulatory and inhibitory Smads, and how they may be perturbed in tumor cells, is important. TGF-β exhibits numerous effects that are dependent on the cell type and context, and often appear to be conflicting. Crosstalk with other signaling pathways may provide one explanation that the biological response to TGF-β is often dependent on the extracellular environment of the cell. New therapeutic opportunities may develop from a clearer and more in-depth understanding of the TGF-β signal transduction pathway and the molecular and cellular contexts that permit the tumor suppressor or pro-oncogenic activities of TGF-β.