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

Wilkes, Mark C., Repellin, Claire E., Kang, Jeong-Han, Andrianifahanana, Mahefatiana, Yin, Xueqian, and Leof, Edward B. (2015) Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor ß signaling. Molecular Biology of the Cell, 26. pp. 3879-3891.

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Abstract

Transforming growth factor ß (TGFß) is a pleiotropic protein secreted from essentially all cell types and primary tissues. While TGFß's actions reflect the activity of a number of signaling networks, the primary mediator of TGFß 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 ß importins (Imp7 or Impß), it mediates the association of pSmad3 with Imp8 and the nuclear membrane. This facilitates nuclear translocation of pSmad3 but not SNX9.

Item ID: 44411
Item Type: Article (Research - C1)
ISSN: 1939-4586
Additional Information:

© 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).

Funders: National Institute of General Medical Sciences (NIGMS), Caerus Foundation, Scleroderma Foundation, Mayo Foundation
Projects and Grants: NIGMS GM-55816, NIGMS GM-54200
Date Deposited: 20 Jun 2016 00:19
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111601 Cell Physiology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 50%
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