論文 - 詳細
| RRC ID | 86346 |
|---|---|
| 著者 | Teratake Y, Okamura T, Ishizaka Y. |
| タイトル | SMAD5 phosphorylation by ALK1 is modulated by the interaction of the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2. |
| ジャーナル | Antiviral Res |
| Abstract |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 7 million worldwide deaths, but the mechanisms underlying its severe clinical outcomes remain elusive. Although attachment of the spike (S) protein of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2), a pivotal step for infection, induces inflammation, the intracellular signals triggered by this interaction are unclear. Here, we found that S protein induced phosphorylation of SMAD family member 5 which was mediated by the bone morphologenetic protein (BMP) receptor activin receptor-like kinase 1 (ALK1) and BMP receptor type II. SMAD5 activation depended on the interaction of the cytoplasmic domains of ACE2 and ALK1. Notably, repetitive treatment with S protein increased the expression of immune-response genes, including interferon regulatory factor 1, interleukin-17A, and cysteine-cysteine chemokine motif ligand 20 (CCL20), all of which were blocked by an ALK inhibitor. In contrast, the S protein of human coronavirus NL63, a pathogen of acute respiratory infection with less severity than SARS-CoV-2 that also binds to ACE2, did not activate SMAD5. Because CCL20 recruits multiple immune cells positive for CC receptor 6, a specific receptor for CCL20, and was detected in broncho-alveolar lavage fluids of patients with respiratory failures by SARS-Cov-2, data suggest that SMAD5 activation by S protein augments the early immune response, leading to the severe clinical outcomes of SARS-CoV-2. |
| 巻・号 | 242 |
| ページ | 106261 |
| 公開日 | 2025-10-1 |
| DOI | 10.1016/j.antiviral.2025.106261 |
| PII | S0166-3542(25)00187-1 |
| PMID | 40835031 |
| MeSH | Activin Receptors, Type II* / metabolism Angiotensin-Converting Enzyme 2* / metabolism COVID-19 / metabolism HEK293 Cells Humans Phosphorylation Protein Binding SARS-CoV-2* / metabolism Smad5 Protein* / metabolism Spike Glycoprotein, Coronavirus* / metabolism |
| IF | 4.101 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) |