Divergence and convergence of TGF-β/BMP signaling

Abstract

The transforming growth factor-β (TGF-β) superfamily includes more than 30 members which have a broad array of biological activities. TGF-β superfamily ligands bind to type II and type I serine/threonine kinase receptors and transduce signals via Smad proteins. Receptor-regulated Smads (R-Smads) can be classified into two subclasses, i.e. those activated by activin and TGF-β signaling pathways (AR-Smads), and those activated by bone morphogenetic protein (BMP) pathways (BR-Smads). The numbers of type II and type I receptors and Smad proteins are limited. Thus, signaling of the TGF-β superfamily converges at the receptor and Smad levels. In the intracellular signaling pathways, Smads interact with various partner proteins and thereby exhibit a wide variety of biological activities. Moreover, signaling by Smads is modulated by various other signaling pathways allowing TGF-β superfamily ligands to elicit diverse effects on target cells. Perturbations of the TGF-β/BMP signaling pathways result in various clinical disorders including cancers, vascular diseases, and bone disorders. © 2001 Wiley-Liss, Inc.