TGF-beta signaling by Smad proteins

Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):15-22. doi: 10.1016/s1359-6101(99)00025-8.

Abstract

Smads are signal transducers for the members of the transforming growth factor-beta (TGF-beta) superfamily. Bone morphogenetic proteins (BMPs) and their receptors induce differentiation of C2C12 cells into osteoblast-like cells. Using an adenoviral expression vector system, we showed that receptor-regulated Smads (R-Smads) activated by BMPs can induce the differentiation of C2C12 cells. Inhibitory Smads (I-Smads) interfere with the osteoblast differentiation of C2C12 cells by preventing the nuclear translocation of R-Smads. After translocation into the nucleus, Smad oligomers regulate the transcription of target genes through binding to DNA directly, interaction with other DNA binding proteins, and recruitment of transcriptional co-activators or co-repressors. Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein Receptors
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Differentiation / drug effects
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Cell Surface / metabolism
  • Receptors, Growth Factor*
  • Signal Transduction*
  • Smad Proteins
  • Smad1 Protein
  • Smad5 Protein
  • Smad6 Protein
  • Smad7 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • SMAD1 protein, human
  • SMAD5 protein, human
  • SMAD6 protein, human
  • SMAD7 protein, human
  • Smad Proteins
  • Smad1 Protein
  • Smad5 Protein
  • Smad6 Protein
  • Smad7 Protein
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • SKI protein, human
  • Bone Morphogenetic Protein Receptors