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Updated: Feb 16, 2026

Bioorthogonal Chemical Imaging of Cell Metabolism Regulated by Aromatic Amino Acids
Published on: May 12, 2023
Amino acid and small GTPase regulation of mTORC1
Thu P Nguyen1,2, Anderson R Frank1,2, Jenna L Jewell1,2
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX USA.
Abstract:
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that belongs to the phosphatidylinositol 3-kinase-related kinase (PIKK) family. mTOR is the catalytic subunit of mTOR complex 1 (mTORC1), which integrates multiple environmental signals to control cell growth and metabolism. Nutrients, specifically amino acids, are the most potent stimuli for mTORC1 activation. Multiple studies have focused on how leucine and arginine activate mTORC1 through the Rag GTPases, with mechanistic details slowly emerging. Recently, a Rag GTPase-independent glutamine signaling pathway to mTORC1 has been identified, suggesting that mTORC1 is differentially regulated through distinct pathways by specific amino acids. In this review, we summarize our current understanding of how amino acids modulate mTORC1, and the role of other small GTPases in the regulation of mTORC1 activity.
Insights
Amino acids regulate cell growth via the mammalian target of rapamycin (mTOR) kinase. This review details how specific amino acids activate mTOR complex 1 (mTORC1) through distinct nutrient-sensing pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism.
- mTOR functions as the catalytic subunit of mTOR complex 1 (mTORC1).
- Amino acids are potent stimuli for mTORC1 activation, integrating environmental signals.
Purpose of the Study:
- To review the mechanisms by which amino acids modulate mTORC1 activity.
- To highlight the differential regulation of mTORC1 by specific amino acids.
- To discuss the role of small GTPases in mTORC1 regulation.
Main Methods:
- Literature review of studies on mTORC1 signaling.
- Analysis of nutrient-sensing pathways.
- Focus on Rag GTPase-dependent and -independent mechanisms.
Main Results:
- Leucine and arginine activate mTORC1 via Rag GTPases.
- A distinct, Rag GTPase-independent glutamine pathway to mTORC1 has been identified.
- mTORC1 is differentially regulated by specific amino acids through distinct signaling routes.
Conclusions:
- Amino acid availability is a critical determinant of mTORC1 activity.
- Multiple nutrient-sensing pathways converge on mTORC1.
- Understanding these pathways is crucial for comprehending cell growth and metabolism control.
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