Specificity and versatility in tgf-beta signaling through Smads

Annu Rev Cell Dev Biol. 2005:21:659-93. doi: 10.1146/annurev.cellbio.21.022404.142018.


The TGF-beta family comprises many structurally related differentiation factors that act through a heteromeric receptor complex at the cell surface and an intracellular signal transducing Smad complex. The receptor complex consists of two type II and two type I transmembrane serine/threonine kinases. Upon phosphorylation by the receptors, Smad complexes translocate into the nucleus, where they cooperate with sequence-specific transcription factors to regulate gene expression. The vertebrate genome encodes many ligands, fewer type II and type I receptors, and only a few Smads. In contrast to the perceived simplicity of the signal transduction mechanism with few Smads, the cellular responses to TGF-beta ligands are complex and context dependent. This raises the question of how the specificity of the ligand-induced signaling is achieved. We review the molecular basis for the specificity and versatility of signaling by the many ligands through this conceptually simple signal transduction mechanism.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors / metabolism
  • Forecasting
  • Humans
  • Ligands
  • Models, Biological
  • Receptors, Transforming Growth Factor beta / metabolism
  • Sensitivity and Specificity
  • Signal Transduction*
  • Smad Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / physiology*


  • Ligands
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta
  • Bone Morphogenetic Protein Receptors