TGFβ–SMAD signal transduction molecular specificity and functional flexibility英文文献.pdfVIP

R E V I E W S TGFβ–SMAD signal transduction: molecular specificity and functional flexibility Bernhard Schmierer and Caroline S. Hill Abstract | Ligands of the transforming growth factor‑β (TGFβ) superfamily of growth factors initiate signal transduction through a bewildering complexity of ligand–receptor interactions. Signalling then converges to nuclear accumulation of transcriptionally active SMAD complexes and gives rise to a plethora of specific functional responses in both embryos and adult organisms. Current research is focused on the mechanisms that regulate SMAD activity to evoke cell‑type‑specific and context‑dependent transcriptional programmes. An equally important challenge is understanding the functional role of signal strength and duration. How are these quantitative aspects of the extracellular signal regulated? How are they then sensed and interpreted, and how do they affect responses? Hereditary haemorrhagic Ligands of the TGFβ superfamily of growth factors pathway: ligands, receptors and SMADs. Focusing on data telangiectasia regulate many cellular functions including cell growth, that have been obtained in developmental systems, we An autosomal dominant adhesion, migration, cell-fate determination and dif- discuss the regulation of extracellular ligand availability. disorder that is characterized ferentiation, and apoptosis. Malfunctions in signalling We then review the mechanisms that determine whether a