TGF-β signaling from a three-dimensional perspective:: insight into selection of partners

Members of the transforming growth factor beta (TGF-beta) family, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are potent regulators of cell proliferation, differentiation, migration and apoptosis. They act through binding to and activating serine/threonine kinase receptors on the cell surface and triggering intracellular signaling pathways in which Smad proteins have essential roles. Here, we discuss recent structure-based studies of TGF-betas and BMPs, their receptors, and of Smad proteins, which have unravelled insights into ligand specificity, receptor and Smad activation, as well as new features of Smads as phosphoserine-binding entities.