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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Cellular and molecular life sciences : CMLS
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40434714/ |
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Table of Contents:
- Dual phosphorylation of glycogen synthase kinase 3β differentially integrates metabolic programs to determine T cell immunity across vertebrates. Liang, Wei Geng, Ming Rao, Wenzhuo Li, Kang Zhu, Yating Zheng, Yuying Wei, Xiumei Yang, Jialong Animals Glycogen Synthase Kinase 3 beta Phosphorylation Mice Lymphocyte Activation Oxidative Phosphorylation Glycolysis T-Lymphocytes CD4-Positive T-Lymphocytes Cell Proliferation Mice, Inbred C57BL Signal Transduction CD8-Positive T-Lymphocytes Vertebrates The integration of metabolic programs with T cell signaling establishes a molecular foundation for immune metabolism. As a key metabolic regulator, GSK3β's activity is dynamically modulated by phosphorylation at Ser9 and Tyr216. However, the contribution of these phosphorylation sites on metabolism-driven T cell response remains unclear. Using tilapia and mouse models, we investigated the regulation of GSK3β on T cell metabolism and its evolutionary variation. In tilapia, T cell activation induces GSK3β signaling, linking to both glycolysis and oxidative phosphorylation (OXPHOS). Tyr216 phosphorylation preferentially promotes glycolysis, facilitating T cell activation, proliferation, and antibacterial immunity; while inhibition of Ser9 phosphorylation specifically enhances OXPHOS to sustain T cell responses. Differently, Tyr216 phosphorylation supports both glycolysis and OXPHOS in mouse, ensuring CD4 T and CD8 T cell activation, proliferation, and cytokine production. Although Ser9 phosphorylation controls OXPHOS, its inhibition impairs rather than enhances OXPHOS and CD4 T cell responses in mouse. We thus revealed a previously unknown mechanism underlying T cell metabolism and proposed that, through evolution, GSK3β has restructured the regulatory strategy, enabling bidirectional control of T cell metabolism and immunity in mammals and enhancing the flexibility of the adaptive immune system.