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

Shaw RJ; Kosmatka M; Bardeesy N; Cantley LC et al. · 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.

Tier D because it is mechanistic or in-vitro work (model: LKB1-null MEFs; in vitro kinase assays), not a whole-organism health-outcome study; tier describes study design, not quality -- this is often exactly where causal biology gets established.

At a glance

Evidence tier	D Mechanistic / in vitro / review
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

Target	LKB1 -> AMPK (Thr172)
Model	Mouse cells
Effect	LKB1 directly phosphorylates and activates AMPK; LKB1-null cells fail to activate AMPK under energy stress

Abstract

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 →

Cite this record

Barton, O. (2026). The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress — evidence-graded record SHW2004. In Oliver's mTOR Atlas. https://mtor-atlas.org/study/SHW2004/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SHW2004,
  author       = {Barton, Oliver},
  title        = {{The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress} --- evidence-graded record SHW2004},
  howpublished = {Oliver's mTOR Atlas},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SHW2004/},
  note         = {Dataset DOI: 10.5281/zenodo.22059963}
}

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