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A possible linkage between AMP‐activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway
Abstract
Background: The mammalian target of rapamycin (mTOR) regulates multiple cellular functions including translation in response to nutrients, especially amino acids. AMP‐activated protein kinase (AMPK) modulates metabolism in response to energy demand by responding to changes in AMP. Results: The treatment of SV40‐immortalized human corneal epithelial cells (HCE‐T cells) with 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR), widely used as an AMPK activator, inhibits p70 S6k activities. Altered glucose availability, which regulates AMPK activity, also modulates the activity of p70 S6k. AICAR treatment also inhibits phosphorylation of Thr‐412 in the p70 S6 kinase (p70 S6k), which is indispensable for the activity. Furthermore, over‐expression of mutant AMPK subunits by stable expression in rabbit pulmonary fibroblast cell lines (PS120 cells) also modulates p70 S6k activity. The insensitivity of the rapamycin‐resistant p70 S6k variant to AICAR treatment suggests that the inhibition of p70 S6k is mediated through a common effector, supporting a model whereby mTOR and its downstream effector are controlled by AMPK. Conclusion: These results indicate that the AMPK and mTOR signalling pathways are possibly linked. In addition to the mTOR signal acting as a priming switch that modulates p70 S6k activation, AMPK appears to provide an overriding switch linking p70 S6k regulation to cellular energy metabolism.
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“For example treatment with AICAR inhibits S6K (mTOR effector) activity in a range of mammalian cells [150].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [150]
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Metadata
- Authors
- Kimura, N., Tokunaga, C., Dalal, S., Richardson, C., Yoshino, K., Hara, K., Kemp, B. E., Witters, L. A., Mimura, O., & Yonezawa, K.
- Affiliations
- Hyogo Medical University (JP)
- Biosignal Research Center, Kobe University (JP)
- Dartmouth College (US)
- St Vincents Institute of Medical Research (AU)
- Corresponding author
- Yonezawa, Kazuyoshi
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2003-01
- Volume
- 8
- Issue
- 1
- Pages
- 65-79
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W1993363796
- Cited by
- 372
- References
- 52
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 13 · 2022: 9 · 2021: 11 · 2020: 13 · 2019: 17 · 2018: 7 · 2017: 16 · 2016: 23 · 2015: 21 · 2014: 9 · 2013: 28 · 2012: 13
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-35712, R01DK035712)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- AMPK, mTOR signaling, p70 S6 kinase, AICAR, AMPK activation, glucose availability, energy metabolism, rapamycin resistance, corneal epithelial cells, lung fibroblasts, amino acid signalling, translational regulation
- MeSH terms
- Aminoimidazole Carboxamide, Drug Interactions, Humans, Hypoglycemic Agents, Insulin, Multienzyme Complexes, Phosphorylation, Protein Kinases, Proto-Oncogene Proteins, Ribonucleotides, Tumor Cells, Cultured, Signal Transduction, Protein Serine-Threonine Kinases, Ribosomal Protein S6 Kinases, 70-kDa, Proto-Oncogene Proteins c-akt, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
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