TGF-beta signalling from cell membrane to nucleus through SMAD proteins

Nature. 1997 Dec 4;390(6659):465-71. doi: 10.1038/37284.


The recent identification of the SMAD family of signal transducer proteins has unravelled the mechanisms by which transforming growth factor-beta (TGF-beta) signals from the cell membrane to the nucleus. Pathway-restricted SMADs are phosphorylated by specific cell-surface receptors that have serine/threonine kinase activity, then they oligomerize with the common mediator Smad4 and translocate to the nucleus where they direct transcription to effect the cell's response to TGF-beta. Inhibitory SMADs have been identified that block the activation of these pathway-restricted SMADs.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Cell Nucleus / metabolism*
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Signal Transduction*
  • Smad1 Protein
  • Transforming Growth Factor beta* / metabolism*


  • DNA-Binding Proteins
  • SMAD1 protein, human
  • Smad1 Protein
  • Transforming Growth Factor beta