New insights into TGF-beta-Smad signalling

Trends Biochem Sci. 2004 May;29(5):265-73. doi: 10.1016/j.tibs.2004.03.008.


Transforming growth factor beta (TGF-beta) initiates its diverse cellular responses by binding to and activating specific cell surface receptors that have intrinsic serine/threonine kinase activity. These activated TGF-beta 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-beta responses can be cell-type specific and are dependent on both the concentration of TGF-beta signalling components and the activity of other signal transduction pathways, which can either synergize with or antagonize the TGF-beta pathway. Recent research has provided insights into the specificity determinants of TGF-beta-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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*


  • DNA-Binding Proteins
  • Phosphoproteins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD4 protein, human
  • SMAD5 protein, human
  • SMAD6 protein, human
  • SMAD7 protein, human
  • SMAD9 protein, human
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Smad4 protein, rat
  • Smad5 Protein
  • Smad6 Protein
  • Smad7 Protein
  • Smad8 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Activin Receptors