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Activation of stimulator of interferon genes (STING) induces ADAM17-mediated shedding of the immune semaphorin SEMA4D
https://tokushima-u.repo.nii.ac.jp/records/2011864
https://tokushima-u.repo.nii.ac.jp/records/201186443228484-ae9c-44cc-84e1-c42f83f87069
| 名前 / ファイル | ライセンス | アクション |
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jbc_293_20_7717.pdf (1.45 MB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||
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| 公開日 | 2024-05-21 | |||||||||||||||||
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| アクセス権 | open access | |||||||||||||||||
| 資源タイプ | ||||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||
| 出版社版DOI | ||||||||||||||||||
| 関連識別子 | https://doi.org/10.1074/jbc.RA118.002175 | |||||||||||||||||
| 関連名称 | 10.1074/jbc.RA118.002175 | |||||||||||||||||
| 出版タイプ | ||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||
| タイトル | ||||||||||||||||||
| タイトル | Activation of stimulator of interferon genes (STING) induces ADAM17-mediated shedding of the immune semaphorin SEMA4D | |||||||||||||||||
| タイトル別表記 | ||||||||||||||||||
| その他のタイトル | SEMA4D shedding by STING | |||||||||||||||||
| 著者 |
茂谷, 康
× 茂谷, 康
WEKO
684
× 小迫, 英尊
WEKO
301
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| 抄録 | ||||||||||||||||||
| 内容記述 | Stimulator of interferon genes (STING) is an endoplasmic reticulum–resident membrane protein that mediates cytosolic pathogen DNA–induced innate immunity and inflammatory responses in host defenses. STING is activated by cyclic di-nucleotides and is then translocated to the Golgi apparatus, an event that triggers STING assembly with the downstream enzyme TANK-binding kinase 1 (TBK1). This assembly leads to the phosphorylation of the transcription factor interferon regulatory factor 3 (IRF3), which in turn induces expression of type-I interferon (IFN) and chemokine genes. STING also mediates inflammatory responses independently of IRF3, but these molecular pathways are largely unexplored. Here, we analyzed the RAW264.7 macrophage secretome to comprehensively identify proinflammatory factors released into the extracellular medium upon STING activation. In total, we identified 1299 proteins in macrophage culture supernatants, of which 23 were significantly increased after STING activation. These proteins included IRF3-dependent cytokines, as well as previously unknown targets of STING, such as the immune semaphorin SEMA4D/CD100, which possesses proinflammatory cytokine-like activities. Unlike for canonical cytokines, the expression of the SEMA4D gene was not up-regulated. Instead, upon STING activation, membrane-bound SEMA4D was cleaved into a soluble form, suggesting the presence of a post-translational shedding machinery. Importantly, the SEMA4D shedding was blocked by TMI-1, an inhibitor of the sheddase ADAM metallopeptidase domain 17 (ADAM17) but not by the TBK1 inhibitor BX795. These results suggest that STING activates ADAM17 and that this activation produces soluble proinflammatory SEMA4Dindependently of the TBK1/IRF3-mediated transcriptional pathway. | |||||||||||||||||
| 書誌情報 |
en : Journal of Biological Chemistry 巻 293, 号 20, p. 7717-7726, 発行日 2018-04-04 |
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| 収録物識別子タイプ | ISSN | |||||||||||||||||
| 収録物識別子 | 00219258 | |||||||||||||||||
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| 収録物識別子タイプ | ISSN | |||||||||||||||||
| 収録物識別子 | 1083351X | |||||||||||||||||
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| 収録物識別子タイプ | NCID | |||||||||||||||||
| 収録物識別子 | AA1202441X | |||||||||||||||||
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| 出版者 | American Society for Biochemistry and Molecular Biology | |||||||||||||||||
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| 出版者 | Elsevier | |||||||||||||||||
| 権利情報 | ||||||||||||||||||
| 権利情報 | This is an Open Access article under the CC BY license. | |||||||||||||||||
| EID | ||||||||||||||||||
| 識別子 | 340887 | |||||||||||||||||
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| 言語 | eng | |||||||||||||||||
