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Regulation of mTORC1 by Upstream Stimuli

Chase H Melick1,2,3, Jenna L Jewell1,2,3

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Genes
|August 29, 2020
PubMed

Insights

The mammalian target of rapamycin complex 1 (mTORC1) kinase regulates cell growth and metabolism. This review details how growth factors, nutrients, and signaling molecules control mTORC1 activity, impacting diseases like cancer and aging.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • The mammalian target of rapamycin (mTOR) is a crucial protein kinase regulating fundamental cellular processes.
  • mTOR functions as the catalytic subunit of mTOR complex 1 (mTORC1), a key signaling hub.
  • Dysregulation of mTORC1 signaling is implicated in various human diseases, including cancer, diabetes, and aging.

Purpose of the Study:

  • To review recent advancements in understanding the upstream regulation of mTORC1.
  • To elucidate the mechanisms by which diverse stimuli modulate mTORC1 activity and downstream signaling.
  • To highlight the significance of mTORC1 signaling pathways in human health and disease.

Main Methods:

  • Literature review of peer-reviewed research on mTORC1 regulation.
  • Analysis of signaling pathways involving growth factors, amino acids, and GPCRs.
  • Examination of the roles of phosphorylation and small GTPases in mTORC1 control.

Main Results:

  • Growth factors, amino acids, and G-protein coupled receptors (GPCRs) are identified as major upstream regulators of mTORC1.
  • Phosphorylation events and the activity of small GTPases are critical determinants of mTORC1 signaling.
  • These regulatory inputs converge to control mTORC1's influence on cell growth, metabolism, and autophagy.

Conclusions:

  • mTORC1 integrates multiple upstream signals to orchestrate cellular functions.
  • A comprehensive understanding of mTORC1 regulation is vital for developing therapeutic strategies against diseases linked to its dysregulation.
  • Further research into the intricate network of mTORC1 activators and inhibitors holds promise for future biomedical applications.
Keywords:
G-protein coupled receptorsamino acidsand autophagycell growthkinasesmTORC1metabolismphosphorylationsmall GTPases

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