Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress.
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 as a result of 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.
Sengupta
Shomit
S
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Peterson
Timothy R
TR
Sabatini
David M
DM
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D005502:Food; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011506:Proteins; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D036341:Intercellular Signaling Peptides and Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D011506:Proteins; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors