Smad regulation in TGF-beta signal transduction

J Cell Sci. 2001 Dec;114(Pt 24):4359-69.

Abstract

Smad proteins transduce signals from transforming growth factor-beta (TGF-beta) superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. Phosphorylation of receptor-activated Smads (R-Smads) leads to formation of complexes with the common mediator Smad (Co-Smad), which are imported to the nucleus. Nuclear Smad oligomers bind to DNA and associate with transcription factors to regulate expression of target genes. Alternatively, nuclear R-Smads associate with ubiquitin ligases and promote degradation of transcriptional repressors, thus facilitating target gene regulation by TGF-beta. Smads themselves can also become ubiquitinated and are degraded by proteasomes. Finally, the inhibitory Smads (I-Smads) block phosphorylation of R-Smads by the receptors and promote ubiquitination and degradation of receptor complexes, thus inhibiting signalling.

Publication types

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

MeSH terms

  • Activin Receptors, Type I / metabolism*
  • Activin Receptors, Type I / physiology
  • Animals
  • DNA-Binding Proteins / physiology
  • Humans
  • Phosphoproteins / physiology
  • Protein-Serine-Threonine Kinases
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction / physiology*
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Smad5 Protein
  • Smad8 Protein
  • Trans-Activators / physiology
  • Transforming Growth Factor beta / physiology*

Substances

  • DNA-Binding Proteins
  • Phosphoproteins
  • Receptors, Transforming Growth Factor beta
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD4 protein, human
  • SMAD5 protein, human
  • SMAD8 protein, human
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Smad4 protein, rat
  • Smad5 Protein
  • Smad8 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Receptor Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Tgfbr1 protein, rat