{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Cormerais Y"],"funding":["NICHD NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pubmed_abstract":["Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates diverse intracellular and extracellular 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 are unknown. Here, we characterize a genetic mouse model lacking the 5 phosphorylation sites on the tuberous sclerosis complex 2 (TSC2) protein through which the growth factor-stimulated protein kinase AKT can active 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 brain and skeletal muscle, associated with cell intrinsic decreases in growth factor-stimulated mTORC1 signaling. The TSC2-5A mouse model demonstrates that TSC2 phosphorylation is a primary mechanism of mTORC1 activation in some, but not all, tissues and provides a genetic tool to facilitate studies on the physiological regulation of mTORC1."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.09.23.614519"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11463511"],"repository":["biostudies-literature"],"pubmed_title":["AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth."],"pmcid":["PMC11463511"],"funding_grant_id":["R35 CA197459","T32 DK128781","T32 HL007118","F31 DK128873","P50 HD105351","P01 CA120964"],"pubmed_authors":["Cormerais Y","Schrotter S","Lapp SC","Martin ER","Shin J","Personnaz J","Manning BD","Byles V","Cisse MY","Stefadu B","Salussolia CL","Menon S","D'Amore A","Sahin M","Kalafut KC"],"additional_accession":[]},"is_claimable":false,"name":"AKT-mediated phosphorylation of TSC2 controls stimulus- and tissue-specific mTORC1 signaling and organ growth.","description":"Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates diverse intracellular and extracellular 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 are unknown. Here, we characterize a genetic mouse model lacking the 5 phosphorylation sites on the tuberous sclerosis complex 2 (TSC2) protein through which the growth factor-stimulated protein kinase AKT can active 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 brain and skeletal muscle, associated with cell intrinsic decreases in growth factor-stimulated mTORC1 signaling. The TSC2-5A mouse model demonstrates that TSC2 phosphorylation is a primary mechanism of mTORC1 activation in some, but not all, tissues and provides a genetic tool to facilitate studies on the physiological regulation of mTORC1.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-05-06T03:20:18.05Z","creation":"2025-04-06T22:39:36.025Z"},"accession":"S-EPMC11463511","cross_references":{"pubmed":["39386441"],"doi":["10.1101/2024.09.23.614519"]}}