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Title: Arl15 upregulates the TGFβ family signaling by promoting the assembly of the Smad-complex
Authors: Shi, Meng
Tie, Hieng Chiong
Divyanshu, Mahajan
Sun, Xiuping
Zhou, Yan
Boh, Boon Kim
Vardy, Leah A.
Lu, Lei
Keywords: Science::Biological sciences
Issue Date: 2022
Source: Shi, M., Tie, H. C., Divyanshu, M., Sun, X., Zhou, Y., Boh, B. K., Vardy, L. A. & Lu, L. (2022). Arl15 upregulates the TGFβ family signaling by promoting the assembly of the Smad-complex. ELife, 11, e76146-.
Project: AcRF Tier1 RG35/17 
Tier2 MOE2015-T2-2-073 
Journal: eLife 
Abstract: The hallmark event of the canonical transforming growth factor β (TGFβ) family signaling is the assembly of the Smad-complex, consisting of the common Smad, Smad4, and phos-phorylated receptor-regulated Smads. How the Smad-complex is assembled and regulated is still unclear. Here, we report that active Arl15, an Arf-like small G protein, specifically binds to the MH2 domain of Smad4 and colocalizes with Smad4 at the endolysosome. The binding relieves the auto-inhibition of Smad4, which is imposed by the intramolecular interaction between its MH1 and MH2 domains. Activated Smad4 subsequently interacts with phosphorylated receptor-regulated Smads, forming the Smad-complex. Our observations suggest that Smad4 functions as an effector and a GTPase activating protein (GAP) of Arl15. Assembly of the Smad-complex enhances the GAP activity of Smad4 toward Arl15, therefore dissociating Arl15 before the nuclear translocation of the Smad-complex. Our data further demonstrate that Arl15 positively regulates the TGFβ family signaling.
ISSN: 2050-084X
DOI: 10.7554/ELIFE.76146
DOI (Related Dataset): 10.21979/N9/WRFNC2
Schools: School of Biological Sciences 
Rights: © Shi et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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