New insights into extracellular and post-translational regulation of TGF-β family signalling pathways.

Members of the transforming growth factor-β (TGF-β) family of secreted proteins are present in all multicellular animals. TGF-β proteins are versatile intercellular signalling molecules that orchestrate cell fate decisions during development and maintain homeostasis in adults. The Smad family of signal transducers implements TGF-β signals in responsive cells. Given the ability of TGF-β ligands to induce dramatic responses in target cells, numerous regulatory mechanisms exist to prevent unintended consequences. Here we review new reports of extracellular and post-translational regulation in Drosophila and vertebrates. Extracellular topics include the regulation of TGF-β signalling range and the coordination between tissue morphogenesis and TGF-β signalling. Post-translational topics include the regulation of TGF-β signal transduction by Gsk3-β phosphorylation of Smads and by cycles of Smad mono- and deubiquitylation. Extension of the ubiquitylation data to the Hippo pathway is also discussed.