Signal transduction by bone morphogenetic protein receptors: functional roles of Smad proteins

Bone. 1999 Jul;25(1):91-3. doi: 10.1016/s8756-3282(99)00113-1.

Abstract

Intracellular signals for bone morphogenetic proteins (BMPs) and other members in the transforming growth factor (TGF)-beta superfamily are mediated by Smad proteins. Receptor-regulated Smads (R-Smads) are activated by serine/threonine kinase receptors upon ligand binding. R-Smads then form hetero-oligomeric complexes with a common-mediator Smad (co-Smad) and translocate into the nucleus, where they regulate transcription of target genes. Smads 1, 5, and 8 are R-Smads activated by BMP receptors, whereas Smads 2 and 3 are activated by TGF-beta and activin receptors. Smad4 is the only co-Smad isolated in mammals, and is shared by BMP and TGF-beta/activin signaling pathways. Smads 6 and 7 are anti-Smads, which block signals by preventing the activation of R-Smads by serine/threonine kinase receptors. Anti-Smads are induced by ligand stimulation, suggesting that they constitute a negative feedback loop in the signal transduction pathways of the TGF-beta superfamily.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Protein Receptors
  • DNA-Binding Proteins / physiology*
  • Feedback
  • Multigene Family*
  • Receptors, Cell Surface / physiology*
  • Receptors, Growth Factor*
  • Signal Transduction / physiology*
  • Structure-Activity Relationship
  • Transforming Growth Factor beta / genetics*

Substances

  • DNA-Binding Proteins
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Transforming Growth Factor beta
  • Bone Morphogenetic Protein Receptors