TGF-beta: Receptors and cell cycle arrest

Transforming growth factor-beta (TGF-beta) is the prototypic member of a superfamily of proteins important in normal growth and development. The recent molecular cloning and characterization of TGF-beta receptors represents a major advance in our understanding of the mechanism of action of this cytokine. These studies have revealed that TGF-beta elicits its diverse biological responses following the formation of a heteromeric complex involving two distantly related transmembrane serine/threonine kinases, both of which are required for signalling. Furthermore, there has been very rapid progress in the identification of key components that regulate the cell cycle, including the cyclin-dependent kinases (CDKs) and their partners, the cyclins. Perhaps the most significant development has been the isolation of a family of proteins that bind to and inactivate CDKs. The ability of TGF-beta to regulate the action of these CDK inhibitors results in growth arrest of mammalian cells in G1.