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Biochem Soc Trans DOI:10.1042/BST20130063

Nutrients and growth factors in mTORC1 activation.

Publication TypeJournal Article
Year of Publication2013
AuthorsEfeyan, A, Sabatini, DM
JournalBiochem Soc Trans
Date Published2013 Aug
KeywordsAnimals, Animals, Newborn, Growth Substances, Humans, Mice, Models, Molecular, Multiprotein Complexes, TOR Serine-Threonine Kinases

Growth factors and nutrients regulate the mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] by different mechanisms. The players that link growth factors and mTORC1 activation have been known for several years and mouse models have validated its relevance for human physiology and disease. In contrast with the picture for growth factor signalling, the means by which nutrient availability leads to mTORC1 activation have remained elusive until recently, with the discovery of the Rag GTPases upstream of mTORC1. The Rag GTPases recruit mTORC1 to the outer lysosomal surface, where growth factor signalling and nutrient signalling converge on mTORC1 activation. A mouse model of constitutive RagA activity has revealed qualitative differences between growth-factor- and nutrient-dependent regulation of mTORC1. Regulation of mTORC1 activity by the Rag GTPases in vivo is key for enduring early neonatal starvation, showing its importance for mammalian physiology.


Alternate JournalBiochem. Soc. Trans.
PubMed ID23863153
PubMed Central IDPMC3845370
Grant ListAG042876 / AG / NIA NIH HHS / United States
AI047389 / AI / NIAID NIH HHS / United States
CA103866 / CA / NCI NIH HHS / United States
R21 AG042876 / AG / NIA NIH HHS / United States
CA129105 / CA / NCI NIH HHS / United States
R01 CA129105 / CA / NCI NIH HHS / United States