The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR
Open accessAbstract
The serine/threonine kinase ULK1 is a mammalian homolog of Atg1, part of the Atg1 kinase complex, which is the most upstream component of the core autophagy machinery conserved from yeast to mammals. In budding yeast, activity of the Atg1 kinase complex is inhibited by TORC1 (target of rapamycin complex 1), but how the counterpart ULK1 complex in mammalian cells is regulated has been unknown. Our laboratories recently discovered that AMPK associates with, and directly phosphorylates, ULK1 on several sites and this modification is required for ULK1 activation after glucose deprivation. In contrast, when nutrients are plentiful, the mTORC1 complex phosphorylates ULK1, preventing its association and activation by AMPK. These studies have revealed a molecular mechanism of ULK1 regulation by nutrient signals via the actions of AMPK and mTORC1.
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“Under glucose starvation, AMPK apparently promotes autophagy by directly activating ULK1 through phosphorylation, although the exact AMPK-mediated ULK1 phosphorylation site(s) remains controversial (Table 2) [665, 669-671].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [671]
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“Endurance training has been shown to inhibit mTOR/p70 S6K signaling and reduce IRS1 serine phosphorylation in rat skeletal muscle [157], and recent studies have demonstrated that AMPK is involved in the suppression of mTOR signaling [39].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [39]
In the citing paper
“Presumably, AMPK antagonizes the autophagy-inhibitory effect of amino acids (at the level of phagophore assembly) by phosphorylating proteins involved in MTORC1 signaling, such as TSC2 [668] and RPTOR/raptor [668] as well as the MTORC1 target ULK1 (see below) [669-671].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [671]
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Citations
Cites
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Self-citationPhosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600
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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationAutophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134
Targeting Autophagy in Cancer: Recent Advances and Future Directions
Amaravadi, R. K., Kimmelman, A. C., & Debnath, J. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0292 · Cited by 928
Metadata
- Authors
- Egan, D., Kim, J., Shaw, R. J., & Guan, K.-L.
- Affiliations
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Corresponding author
- Shaw, Reuben J.
- Guan, Kun-Liang
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2011-06
- Volume
- 7
- Issue
- 6
- Pages
- 643-644
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC3359466
- OpenAlex
- W2070871404
- Cited by
- 627
- References
- 2
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 51 · 2023: 33 · 2022: 53 · 2021: 61 · 2020: 57 · 2019: 54 · 2018: 49 · 2017: 56 · 2016: 41 · 2015: 34 · 2014: 42 · 2013: 19 · 2012: 25
- FWCI
- 21.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA108941)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- 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
- Keywords
- ULK1, autophagy initiation, AMPK, mTORC1, protein phosphorylation, nutrient signaling, glucose deprivation, TOR signaling, kinase regulation
- MeSH terms
- Autophagy-Related Protein-1 Homolog, Mechanistic Target of Rapamycin Complex 1, Adenylate Kinase, Animals, Autophagy, Saccharomycetales, Glucose, Humans, Models, Biological, Phosphorylation, Proteins, Gene Expression Regulation, Fungal, Caenorhabditis elegans, Protein Serine-Threonine Kinases, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, Mice, TOR Serine-Threonine Kinases
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