Transforming Growth Factor-beta Receptors: Role in Physiology and Disease

Transforming growth factor-beta (TGF-beta) 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 organism underscore the essential nature of this family of molecules. The effects of TGF-beta are mediated by a family of dedicated receptors, the TGF-beta 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-beta type II receptor should be considered a tumor suppressor gene. High levels of mutation in the TGF-beta 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-beta type II receptor gene represents a very critical step in the pathway of carcinogenesis. Copyright 1996 S. Karger AG, Basel