The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress

Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC · 2004 · Proceedings of the National Academy of Sciences · Atlas ID SHW2004

What this study shows

The paper that identified LKB1 as the upstream kinase for AMPK: LKB1 directly phosphorylates AMPK-alpha on Thr172, and LKB1-null cells cannot activate AMPK under energy stress. This is the canonical source for the LKB1 -> AMPK step that gates the whole energy-sensing arm upstream of mTORC1.

Abstract

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AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types.

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: LKB1-null MEFs; in vitro kinase assays) 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	LKB1-null MEFs; in vitro kinase assays
Journal	Proceedings of the National Academy of Sciences
Year	2004
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1073/pnas.0308061100 · PMID 14985505

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	LKB1 loss (LKB1-null MEFs); in vitro phosphorylation of AMPK by LKB1
Target	LKB1 -> AMPK (AMPKalpha Thr172)
Model	Mouse embryonic fibroblasts; in vitro kinase assays
Effect	LKB1 directly phosphorylates and activates AMPK; without LKB1, AMPK is not activated by energy stress and cells are more prone to apoptosis

In the Atlas

Links in the pathway map

Supports LKB1 (STK11) activates AMPK

Cite this paper

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Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004). The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0308061100

@article{SHW2004,
  author       = {Shaw, R. J. and Kosmatka, M. and Bardeesy, N. and Hurley, R. L. and Witters, L. A. and DePinho, R. A. and Cantley, L. C.},
  title        = {{The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress}},
  journal      = {Proceedings of the National Academy of Sciences},
  year         = {2004},
  doi          = {10.1073/pnas.0308061100},
  note         = {PMID: 14985505},
}

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 SHW2004) [Data set]. https://mtor-atlas.org/study/SHW2004/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHW2004,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SHW2004},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHW2004/},
  doi          = {10.5281/zenodo.22059963}
}

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