PPM1A dephosphorylates RanBP3 to enable efficient nuclear export of Smad2 and Smad3

EMBO Rep. 2011 Oct 28;12(11):1175-81. doi: 10.1038/embor.2011.174.

Abstract

Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription factors in the canonical transforming growth factor-β (TGF-β) signalling pathway. Active Smad2/3 signalling in the nucleus is terminated by dephosphorylation and subsequent nuclear export of Smad2/3. Here we report that protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3. PPM1A directly interacted with and dephosphorylated RanBP3 at Ser 58 in vitro and in vivo. Consistently, RanBP3 phosphorylation was elevated in PPM1A-null mouse embryonic fibroblasts. Dephosphorylation of RanBP3 at Ser 58 promoted its ability to export Smad2/3 and terminate TGF-β responses. Our findings indicate the critical role of PPM1A in maximizing exporter activity of RanBP3 for efficient termination of canonical TGF-β signalling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Substitution / genetics
  • Animals
  • Cell Nucleus / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Biological
  • Mutant Proteins / metabolism
  • Nuclear Proteins / metabolism*
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Phosphatase 2C
  • Signal Transduction
  • Smad2 Protein / metabolism*
  • Smad3 Protein / metabolism*
  • Substrate Specificity
  • Transforming Growth Factor beta

Substances

  • Mutant Proteins
  • Nuclear Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta
  • PPM1A protein, human
  • Phosphoprotein Phosphatases
  • Ppm1a protein, mouse
  • Protein Phosphatase 2C