Two major Smad pathways in TGF-beta superfamily signalling

Genes Cells. 2002 Dec;7(12):1191-204. doi: 10.1046/j.1365-2443.2002.00599.x.


Members of the transforming growth factor-beta (TGF-beta) superfamily bind to two different serine/threonine kinase receptors, i.e. type I and type II receptors. Upon ligand binding, type I receptors specifically activate intracellular Smad proteins. R-Smads are direct substrates of type I receptors; Smads 2 and 3 are specifically activated by activin/nodal and TGF-beta type I receptors, whereas Smads 1, 5 and 8 are activated by BMP type I receptors. Nearly 30 proteins have been identified as members of the TGF-beta superfamily in mammals, and can be classified based on whether they activate activin/TGF-beta-specific R-Smads (AR-Smads) or BMP-specific R-Smads (BR-Smads). R-Smads form complexes with Co-Smads and translocate into the nucleus, where they regulate the transcription of target genes. AR-Smads bind to various proteins, including transcription factors and transcriptional co-activators or co-repressors, whereas BR-Smads interact with other proteins less efficiently than AR-Smads. Id proteins are induced by BR-Smads, and play important roles in exhibiting some biological effects of BMPs. Understanding the mechanisms of TGF-beta superfamily signalling is thus important for the development of new ways to treat various clinical diseases in which TGF-beta superfamily signalling is involved.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / classification
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Multigene Family
  • Phylogeny
  • Protein Structure, Tertiary
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction / physiology*
  • Smad Proteins
  • Trans-Activators / chemistry
  • Trans-Activators / classification
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transforming Growth Factor beta / metabolism*


  • DNA-Binding Proteins
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Trans-Activators
  • Transforming Growth Factor beta