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

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 c...

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Autores principales: Wilkes, Mark C., Repellin, Claire E., Kang, Jeong-Han, Andrianifahanana, Mahefatiana, Yin, Xueqian, Leof, Edward B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626071/
https://www.ncbi.nlm.nih.gov/pubmed/26337383
http://dx.doi.org/10.1091/mbc.E15-07-0545
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author Wilkes, Mark C.
Repellin, Claire E.
Kang, Jeong-Han
Andrianifahanana, Mahefatiana
Yin, Xueqian
Leof, Edward B.
author_facet Wilkes, Mark C.
Repellin, Claire E.
Kang, Jeong-Han
Andrianifahanana, Mahefatiana
Yin, Xueqian
Leof, Edward B.
author_sort Wilkes, Mark C.
collection PubMed
description 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.
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spelling pubmed-46260712016-01-16 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. Mol Biol Cell Articles 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. The American Society for Cell Biology 2015-11-01 /pmc/articles/PMC4626071/ /pubmed/26337383 http://dx.doi.org/10.1091/mbc.E15-07-0545 Text en © 2015 Wilkes, Repellin, Kang, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
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
title Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling
title_full Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling
title_fullStr Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling
title_full_unstemmed Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling
title_short Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling
title_sort sorting nexin 9 differentiates ligand-activated smad3 from smad2 for nuclear import and transforming growth factor β signaling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626071/
https://www.ncbi.nlm.nih.gov/pubmed/26337383
http://dx.doi.org/10.1091/mbc.E15-07-0545
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