1. Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc.
- Author
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Li M, Lazorchak AS, Ouyang X, Zhang H, Liu H, Arojo OA, Yan L, Jin J, Han Y, Qu G, Fu Y, Xu X, Liu X, Zhang W, Yang Z, Ruan C, Wang Q, Liu D, Huang C, Lu L, Jiang S, Li F, and Su B
- Subjects
- Animals, B-Lymphocytes immunology, Cell Proliferation, Cells, Cultured, Mechanistic Target of Rapamycin Complex 1 genetics, Mechanistic Target of Rapamycin Complex 2 genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation, Proto-Oncogene Proteins c-myc genetics, Signal Transduction, B-Lymphocytes cytology, B-Lymphocytes metabolism, Carrier Proteins physiology, Mechanistic Target of Rapamycin Complex 1 metabolism, Mechanistic Target of Rapamycin Complex 2 metabolism, Proto-Oncogene Proteins c-myc metabolism
- Abstract
Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity, but the underlying molecular mechanisms remain incompletely understood. In this study, Sin1, a key component of mTOR complex 2 (mTORC2), specifically regulates B cell growth and metabolism. Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism. Sin1 deficiency also severely impairs B-cell proliferation, antibody responses, and anti-viral immunity. At the molecular level, Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2, respectively. Therefore, our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.
- Published
- 2019
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