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

MC Wilkes, CE Repellin, JH Kang… - Molecular biology of …, 2015 - Am Soc Cell Biol
MC Wilkes, CE Repellin, JH Kang, M Andrianifahanana, X Yin, EB Leof
Molecular biology of the cell, 2015Am Soc Cell Biol
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 …
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.
Am Soc Cell Biol