AMPK phosphorylation of raptor mediates a metabolic checkpoint

Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ · 2008 · Molecular Cell · Atlas ID GWI2008

What this study shows

Found a SECOND way the energy sensor AMPK shuts mTORC1 down. Besides acting through TSC2, AMPK directly phosphorylates Raptor - the core mTORC1 subunit - to halt growth when energy runs low. This 'metabolic checkpoint' is exactly the switch that drugs like metformin and exercise tap into.

Abstract

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AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain responsive to energy stress. Using a proteomic and bioinformatics approach, we sought to identify additional substrates of AMPK that mediate its effects on growth control.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human/mouse cells (biochemistry)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human/mouse cells (biochemistry)
Journal	Molecular Cell
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.molcel.2008.03.003 · PMID 18439900 · Free full text (PMC2674027)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Biochemical/genetic (AMPK phosphorylation of raptor)
Target	raptor / mTORC1 / AMPK
Model	Human/mouse cells (biochemistry)
Effect	Under energy stress AMPK phosphorylates raptor → a metabolic checkpoint that suppresses mTORC1

In the Atlas

Links in the pathway map

Supports AMPK inhibits mTORC1
Supports Energy & cellular stress activates AMPK

Open questions that cite this study

Cited as supporting evidence for the open question Rapamycin + AMPK-axis drugs (acarbose / metformin): a male-mouse survival signal from cross-cohort comparison, untested in humans.

Cite this paper

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Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008). AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular Cell. https://doi.org/10.1016/j.molcel.2008.03.003

@article{GWI2008,
  author       = {Gwinn, D. M. and Shackelford, D. B. and Egan, D. F. and Mihaylova, M. M. and Mery, A. and Vasquez, D. S. and Turk, B. E. and Shaw, R. J.},
  title        = {{AMPK phosphorylation of raptor mediates a metabolic checkpoint}},
  journal      = {Molecular Cell},
  year         = {2008},
  doi          = {10.1016/j.molcel.2008.03.003},
  note         = {PMID: 18439900},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GWI2008) [Data set]. https://mtor-atlas.org/study/GWI2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GWI2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GWI2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GWI2008/},
  doi          = {10.5281/zenodo.22059963}
}

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