Transforming growth factor-β receptors: Role in physiology and disease

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Abstract
Transforming growth factor-β (TGF-β) plays a pivotal role in numerous vital cellular activities, most significantly the regulation of cellular proliferation and differentiation and synthesis of extracellular matrix components. Its ubiquitous presence in different tissues and strict conservation of nucleotide sequence down through the most primitive vertebrate organisms underscore the essential nature of this family of molecules. The effects of TGF-β are mediated by a family of dedicated receptors, the TGF-β types I, II, and III receptors. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors or their cognate ligands. The coding sequence of the human type II receptor appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. There are now substantial data suggesting that TGF-β type II receptor should be considered a tumor suppressor gene. High levels of mutation in the TGF-β type II receptor gene have been observed in a wide variety of primarily epithelial malignancies, including colon, gastric, and hepatic cancer. It appears likely that mutation of the TGF-β type II receptor gene represents a very critical step in the pathway of carcinogenesis.