Arl15 upregulates the TGFβ family signaling by promoting the assembly of the Smad-complex
| Autor: | Meng Shi, Hieng Chiong Tie, Mahajan Divyanshu, Xiuping Sun, Yan Zhou, Boon Kim Boh, Leah A Vardy, Lei Lu |
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| Přispěvatelé: | School of Biological Sciences |
| Rok vydání: | 2021 |
| Předmět: |
animal structures
General Immunology and Microbiology General Neuroscience Biological sciences [Science] General Medicine General Biochemistry Genetics and Molecular Biology digestive system diseases Transactivator Protein Transforming Growth Factor beta embryonic structures Trans-Activators Smad3 Protein Smad4 Protein Signal Transduction |
| DOI: | 10.1101/2021.12.14.472727 |
| Popis: | 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. Ministry of Education (MOE) Published version This work was supported by the following grants: MOE AcRF Tier1 RG35/17, Tier2 MOE2015-T2-2-073, and MOE2018-T2-2-026. |
| Databáze: | OpenAIRE |
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