Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity.
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| Natura: | Artículo científico |
| Lingua: | en |
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Proceedings of the National Academy of Sciences of the United States of America
2026
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| author | Lai, Wencong Liu, Zengjie Hu, Han Zhang, Wanxuan Li, Baolin Wang, Rui Zhao, Zengqi Li, Xueshan Hu, Yihang Duan, Jinwei Xu, Dan Liu, Yongtao Bu, Xianyong Du, Jianlong Yang, Bingyuan Tang, Xiao Li, Yueru Wan, Min Zhang, Yanjiao Zhou, Huihui Mai, Kangsen Ai, Qinghui |
| author_facet | Lai, Wencong Liu, Zengjie Hu, Han Zhang, Wanxuan Li, Baolin Wang, Rui Zhao, Zengqi Li, Xueshan Hu, Yihang Duan, Jinwei Xu, Dan Liu, Yongtao Bu, Xianyong Du, Jianlong Yang, Bingyuan Tang, Xiao Li, Yueru Wan, Min Zhang, Yanjiao Zhou, Huihui Mai, Kangsen Ai, Qinghui Lai, Wencong Liu, Zengjie Hu, Han Zhang, Wanxuan Li, Baolin Wang, Rui Zhao, Zengqi Li, Xueshan Hu, Yihang Duan, Jinwei Xu, Dan Liu, Yongtao Bu, Xianyong Du, Jianlong Yang, Bingyuan Tang, Xiao Li, Yueru Wan, Min Zhang, Yanjiao Zhou, Huihui Mai, Kangsen Ai, Qinghui |
| collection | PubMed - marine biology |
| contents | Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity. Lai, Wencong Liu, Zengjie Hu, Han Zhang, Wanxuan Li, Baolin Wang, Rui Zhao, Zengqi Li, Xueshan Hu, Yihang Duan, Jinwei Xu, Dan Liu, Yongtao Bu, Xianyong Du, Jianlong Yang, Bingyuan Tang, Xiao Li, Yueru Wan, Min Zhang, Yanjiao Zhou, Huihui Mai, Kangsen Ai, Qinghui Immunity, Innate Protein Serine-Threonine Kinases Animals Phosphorylation Humans Nucleotidyltransferases Diglycerides Interferon Regulatory Factor-3 Protein Kinase C-delta Mice Phosphatidylethanolamines HEK293 Cells Signal Transduction RNA Nucleotidyltransferases Phosphatidylethanolamine (PE) biosynthesis is critical for membrane biology and cellular homeostasis. However, its specific role in antiviral innate immunity remains poorly understood. Here, we demonstrate that inhibition of phosphoethanolamine cytidylyltransferase 2 (PCYT2), a key enzyme in PE biosynthesis, promotes TBK1 activation to enhance the antiviral innate immune response. Mechanistically, PCYT2 deficiency leads to the accumulation of diacylglycerol, which activates protein kinase C-δ (PKCδ). We identify PKCδ as a direct kinase for TBK1 and demonstrate that it binds to and phosphorylates TBK1 at Ser716. This Ser716 phosphorylation facilitates the subsequent canonical phosphorylation of TBK1 at Ser172, resulting in hyperactivation of the TBK1-IRF3 axis. Our findings uncover a link between PE metabolism and antiviral innate immunity, suggesting that targeting the PE biosynthesis pathway could be a potential therapeutic strategy against viral infections. |
| format | Artículo científico |
| id | pubmed_42189991 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Proceedings of the National Academy of Sciences of the United States of America |
| record_format | pubmed |
| spellingShingle | Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity. Lai, Wencong Liu, Zengjie Hu, Han Zhang, Wanxuan Li, Baolin Wang, Rui Zhao, Zengqi Li, Xueshan Hu, Yihang Duan, Jinwei Xu, Dan Liu, Yongtao Bu, Xianyong Du, Jianlong Yang, Bingyuan Tang, Xiao Li, Yueru Wan, Min Zhang, Yanjiao Zhou, Huihui Mai, Kangsen Ai, Qinghui Immunity, Innate Protein Serine-Threonine Kinases Animals Phosphorylation Humans Nucleotidyltransferases Diglycerides Interferon Regulatory Factor-3 Protein Kinase C-delta Mice Phosphatidylethanolamines HEK293 Cells Signal Transduction RNA Nucleotidyltransferases Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity. Lai, Wencong Liu, Zengjie Hu, Han Zhang, Wanxuan Li, Baolin Wang, Rui Zhao, Zengqi Li, Xueshan Hu, Yihang Duan, Jinwei Xu, Dan Liu, Yongtao Bu, Xianyong Du, Jianlong Yang, Bingyuan Tang, Xiao Li, Yueru Wan, Min Zhang, Yanjiao Zhou, Huihui Mai, Kangsen Ai, Qinghui Immunity, Innate Protein Serine-Threonine Kinases Animals Phosphorylation Humans Nucleotidyltransferases Diglycerides Interferon Regulatory Factor-3 Protein Kinase C-delta Mice Phosphatidylethanolamines HEK293 Cells Signal Transduction RNA Nucleotidyltransferases Phosphatidylethanolamine (PE) biosynthesis is critical for membrane biology and cellular homeostasis. However, its specific role in antiviral innate immunity remains poorly understood. Here, we demonstrate that inhibition of phosphoethanolamine cytidylyltransferase 2 (PCYT2), a key enzyme in PE biosynthesis, promotes TBK1 activation to enhance the antiviral innate immune response. Mechanistically, PCYT2 deficiency leads to the accumulation of diacylglycerol, which activates protein kinase C-δ (PKCδ). We identify PKCδ as a direct kinase for TBK1 and demonstrate that it binds to and phosphorylates TBK1 at Ser716. This Ser716 phosphorylation facilitates the subsequent canonical phosphorylation of TBK1 at Ser172, resulting in hyperactivation of the TBK1-IRF3 axis. Our findings uncover a link between PE metabolism and antiviral innate immunity, suggesting that targeting the PE biosynthesis pathway could be a potential therapeutic strategy against viral infections. |
| title | Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity. |
| topic | Immunity, Innate Protein Serine-Threonine Kinases Animals Phosphorylation Humans Nucleotidyltransferases Diglycerides Interferon Regulatory Factor-3 Protein Kinase C-delta Mice Phosphatidylethanolamines HEK293 Cells Signal Transduction RNA Nucleotidyltransferases |
| url | https://pubmed.ncbi.nlm.nih.gov/42189991/ |