Interaction between Smad anchor for receptor activation and Smad3 is not essential for TGF-beta/Smad3-mediated signaling

Biochem Biophys Res Commun. 2001 Mar;281(5):1100-5. doi: 10.1006/bbrc.2001.4489.

Abstract

Regulation of subcellular localization of Smad proteins is supposed to be critical for the effective initiation and maintenance of TGF-beta signaling. Recently, Smad anchor for receptor activation (SARA) has been identified as a Smad2 binding protein. SARA regulates the subcellular localization of Smad2 and is required for TGF-beta/Smad2-mediated signaling. In this study, we determined whether the interaction between SARA and Smad3 is essential for TGF-beta/Smad3-mediated signaling. We found that a mutant Smad3 (Smad3NS) that lacked the binding to SARA was phosphorylated by TGF-beta type I receptor at the similar level to that in wild-type Smad3 (Smad3WT). Smad3NS also formed complexes with Smad4 and translocalized into the nucleus. Moreover, Smad3NS and Smad3WT equally enhanced TGF-beta-induced transcription. Therefore, these findings indicate that, in contrast to SARA/Smad2 interaction, SARA/Smad3 interaction is not essential for TGF-beta/Smad3-mediated signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Activin Receptors, Type I*
  • Animals
  • COS Cells
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endosomal Sorting Complexes Required for Transport
  • Macromolecular Substances
  • Mutation
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction
  • Smad3 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • Transfection
  • Transforming Growth Factor beta / physiology*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Macromolecular Substances
  • Phosphoproteins
  • Receptors, Transforming Growth Factor beta
  • Smad3 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • hepatocyte growth factor-regulated tyrosine kinase substrate
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I