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mTOR Signaling in Growth, Metabolism, and Disease

TLDR
Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR-signaling network contributes to human disease is highlighted.
Abstract
The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.

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Citations
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References
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Journal ArticleDOI

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
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AMPK phosphorylation of raptor mediates a metabolic checkpoint.

TL;DR: AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor, uncovering a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status.
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mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery

TL;DR: It is reported that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.