| First Author | Cormerais Y | Year | 2025 |
| Journal | Dev Cell | Volume | 60 |
| Issue | 19 | Pages | 2544-2557.e7 |
| PubMed ID | 40480230 | Mgi Jnum | J:373020 |
| Mgi Id | MGI:8251093 | Doi | 10.1016/j.devcel.2025.05.008 |
| Citation | Cormerais Y, et al. (2025) AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth. Dev Cell 60(19):2544-2557.e7 |
| abstractText | Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates diverse growth signals to regulate cell and tissue growth. How the molecular mechanisms regulating mTORC1 signaling-established through biochemical and cell biological studies-function under physiological states in specific mammalian tissues is undefined. Here, we characterize a genetic mouse model lacking the five phosphorylation sites on the tuberous sclerosis complex 2 (TSC2) protein through which the growth factor-stimulated protein kinase AKT can activate mTORC1 signaling in cell culture models. These phospho-mutant mice (TSC2-5A) are developmentally normal but exhibit reduced body weight and the weight of specific organs, such as the brain and skeletal muscle, associated with cell-intrinsic decreases in growth factor-stimulated mTORC1 signaling. The TSC2-5A mice demonstrate that TSC2 phosphorylation is a primary mechanism of mTORC1 regulation in response to exogenous signals in some, but not all, tissues and provide a genetic tool to study the physiological regulation of mTORC1. |
