Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress

By Shomit Sengupta, Timothy R. Peterson, David M. Sabatini. Molecules and Cells, 2010

1,256 citations recorded by the source corpus.

Summary The large serine/threonine protein kinase mTOR regulates cellular and organismal homeostasis by coordinating anabolic and catabolic processes with nutrient, energy, and oxygen availability and growth factor signaling. Cells and organisms experience a wide variety of insults that perturb the homeostatic systems governed by mTOR, and therefore require appropriate stress responses to allow cells to continue to function. Stress can manifest from an excess or lack of upstream signals, or due to genetic perturbations in upstream effectors of the pathway. mTOR nucleates two large protein complexes that are important nodes in the pathways that help buffer cells from stresses, and are implicated in the progression of stress-associated phenotypes and diseases, such as aging, tumorigenesis, and diabetes. This review focuses on the key components of the mTOR Complex 1 pathway and on how various stresses impinge upon them.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1794d208471a07bfb68d3d422cd9f61500e70a86

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Regulation of Immune Responses by mTOR (2011, background): “When oxygen, energy, amino acids, and growth factors are readily available, mTOR is active and coordinately promotes cellular processes that facilitate growth such as translation, lipid synthesis, and mitochondrial biogenesis (10, 15).”
Lysosomal positioning coordinates cellular nutrient responses (2011, background): “mTORC1, which contains mTOR and several regulatory subunits including raptor, controls cell metabolism, whereas mTORC2, a rictor-containing complex, modulates actin cytoskeleton dynamic”
The Ras-ERK and PI3K-mTOR Pathways: Cross-talk and Compensation (2011, background): “Among many other substrates involved in these functions, GSK3 also phosphorylates TSC2, thereby activating TSC2 and inactivating mTORC1 [6].”
Translational regulation of gene expression during conditions of cell stress. (2010, background): “, 2010), nutrient deprivation (Sengupta et al., 2010), and DNA damage (Ciccia and Elledge, 2010).”
Sustained axon regeneration induced by co-deletion of PTEN and SOCS3 (2011, background): “Among 15 genes selected, two encode critical positive mTOR regulators, namely small GTPase Rheb and insulin-like growth factor 1 (IGF1”
Glutaminolysis activates Rag-mTORC1 signaling. (2012, background): “…Kim et al., 2002; Loewith et al., 2002; Sarbassov et al., 2004). mTORC1 comprises mTOR, Raptor, and mLST8 and regulates protein synthesis, ribosome biogenesis, nutrient uptake, and autophagy in response to growth factors, amino acids, and cellular energy (Kim and Guan, 2011; Sengupta et al., 2010).”
The Nucleolus under Stress (2010, background): “Under stress conditions that affect cell-cycle progression and/or intracellular energy status, such as nutrient deprivation, alteration of ribosome subunit biosynthesis is one strategy that can preserve cellular energy homeostasis (Sengupta et al., 2010).”
Autophagy and the integrated stress response (2010, positive): “Thus, mTOR is inhibited through multiple mechanisms during starvation conditions (Sengupta et al., 2010).”
The amino acid transporter SLC38A9 is a key component of a lysosomal membrane complex that signals arginine sufficiency to mTORC1 (2015, background): “protein and lipid synthesis, and inhibits catabolic ones, such as autophagy (4).”
Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks (2011, background): “, by phosphorylation of S6K1 and 4E-BP, while simultaneously inhibiting self-consuming processes such as autophagy (94, 110).”