Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling

Mark C. Wilkes, Claire E. Repellin, Jeong Han Kang, Mahefatiana Andrianifahanana, Xueqian Yin, Edward B Leof

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Transforming growth factor β (TGFβ) is a pleiotropic protein secreted from essentially all cell types and primary tissues. While TGFβ's actions reflect the activity of a number of signaling networks, the primary mediator of TGFβ responses are the Smad proteins. Following receptor activation, these cytoplasmic proteins form hetero-oligomeric complexes that translocate to the nucleus and affect gene transcription. Here, through biological, biochemical, and immunofluorescence approaches, sorting nexin 9 (SNX9) is identified as being required for Smad3-dependent responses. SNX9 interacts with phosphorylated (p) Smad3 independent of Smad2 or Smad4 and promotes more rapid nuclear delivery than that observed independent of ligand. Although SNX9 does not bind nucleoporins Nup153 or Nup214 or some β importins (Imp7 or Impβ), it mediates the association of pSmad3 with Imp8 and the nuclear membrane. This facilitates nuclear translocation of pSmad3 but not SNX9.

Original languageEnglish (US)
Pages (from-to)3879-3891
Number of pages13
JournalMolecular Biology of the Cell
Volume26
Issue number21
DOIs
StatePublished - Nov 1 2015

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Sorting Nexins
Cell Nucleus Active Transport
Transforming Growth Factors
Ligands
Smad Proteins
Nuclear Pore Complex Proteins
Karyopherins
Nuclear Envelope
Fluorescent Antibody Technique
Proteins
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling. / Wilkes, Mark C.; Repellin, Claire E.; Kang, Jeong Han; Andrianifahanana, Mahefatiana; Yin, Xueqian; Leof, Edward B.

In: Molecular Biology of the Cell, Vol. 26, No. 21, 01.11.2015, p. 3879-3891.

Research output: Contribution to journalArticle

Wilkes, Mark C. ; Repellin, Claire E. ; Kang, Jeong Han ; Andrianifahanana, Mahefatiana ; Yin, Xueqian ; Leof, Edward B. / Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling. In: Molecular Biology of the Cell. 2015 ; Vol. 26, No. 21. pp. 3879-3891.
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