New insights into TGF-β–Smad signalling

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) Vol. 29; no. 5; pp. 265 - 273
• Main Authors: Dijke, Peter ten, Hill, Caroline S
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2004
• Subjects: Active Transport, Cell Nucleus; Activin Receptors - physiology; Cell Nucleus - metabolism; Cytoplasm - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - physiology; Humans; Models, Biological; Models, Molecular; Phosphoproteins - physiology; Protein Binding; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction - physiology; Smad Proteins; Smad2 Protein; Smad3 Protein; Smad4 Protein; Smad5 Protein; Smad6 Protein; Smad7 Protein; Smad8 Protein; Trans-Activators - chemistry; Trans-Activators - physiology; Transforming Growth Factor beta - physiology
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2004.03.008

Transforming growth factor β (TGF-β) initiates its diverse cellular responses by binding to and activating specific cell surface receptors that have intrinsic serine/threonine kinase activity. These activated TGF-β receptors stimulate the phosphorylation of receptor-regulated Smad proteins, which in turn form complexes with Smad4 that accumulate in the nucleus and regulate the transcription of target genes. TGF-β responses can be cell-type specific and are dependent on both the concentration of TGF-β signalling components and the activity of other signal transduction pathways, which can either synergize with or antagonize the TGF-β pathway. Recent research has provided insights into the specificity determinants of TGF-β–Smad signalling, including combinatorial ligand–receptor associations, selective interactions between the Smads and other pathway components that are mediated through defined binding motifs, and the differential regulation of duration and intensity of signalling.