LKB1 (STK11)
A serine/threonine kinase that activates AMPK and acts upstream of mTOR to regulate cellular energy sensing, autophagy, and metabolism.
The kinase that arms AMPK. An enzyme that switches on AMPK and, through it, helps regulate the cell's energy sensing, cleanup (autophagy), and metabolism - sitting upstream of the mTOR pathway.
Tumour suppressor mutated in Peutz–Jeghers syndrome and in lung adenocarcinoma; also the reason some cells cannot mount an AMPK response at all.
TL;DR. LKB1 (STK11) appears in 4 curated studies in Oliver's mTOR Atlas: 3 in animal models; 1 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| LKB1 (STK11) activates AMPK mechanism: phosphorylation · this link in full · on the map table | LKB1 is the main switch that turns AMPK on when energy runs low; in cells without it, AMPK no longer responds to low energy. A second kinase can still switch AMPK on when calcium rises, so AMPK is not completely silent. LKB1 is the main kinase that primes AMPK, phosphorylating AMPK-alpha directly on Thr172; in LKB1-null cells AMPK no longer responds to energy stress (SHW2004). It is not the only upstream kinase: CaMKK2 phosphorylates the same site when calcium rises, and LKB1-deficient cells keep some basal AMPK activity (Hawley 2005, PMID 16054095; Woods 2005, PMID 16054096; outside this corpus). LKB1 is the main kinase that primes AMPK, phosphorylating AMPK-alpha directly on Thr172; in LKB1-null cells AMPK no longer responds to energy stress (SHW2004). It is not the only upstream kinase: CaMKK2 phosphorylates the same site when calcium rises, and LKB1-deficient cells keep some basal AMPK activity (Hawley 2005, PMID 16054095; Woods 2005, PMID 16054096; outside this corpus). Holds under: Canonical step, established in LKB1-null cells and in vitro kinase assays (SHW2004). Coded M – molecular – because that is what the supporting evidence is: cell and in vitro biochemistry, not an organismal phenotype. plausible in people, not shown directly · settled in the literature | M | SHW2004 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 3 |
| M | Molecular — cells, biochemistry, structure | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | A | LKB1/AMPK deficiency aggravates mitochondrial DNA leakage via mTOR-dependent mitophagy damage in liver injury sensitized by trichloroethylene. ZHU2026 LKB1/AMPK deficiency exacerbates trichloroethylene-induced liver injury by impairing mTOR-regulated mitophagy and causing mitochondrial DNA leakage; rapamycin and AMPK activation are protective, nominating the LKB1/AMPK/mTOR axis as a candidate therapeutic target in mice; no human data. |
| 2026 | A | Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK YAN2026B Hepassocin (HPS/FGL1), a hepatokine, activates AMPK via an ANXA2-ERK-p90RSK-LKB1 cascade, restraining mTOR activity. Aged HPS-knockout mice show reduced LKB1/AMPK activation and elevated mTOR activity, impaired autophagy, exacerbated cellular senescence, and severely compromised liver regeneration after partial hepatectomy. AMPK agonist AICAR or exogenous HPS rescued the aging/regeneration phenotype. |
| 2010 | A | Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state FOR2010 The paper that broke the simple 'metformin works through AMPK' story. Metformin still suppressed hepatic glucose production in mice and hepatocytes lacking AMPK or LKB1, acting instead through a fall in hepatic energy charge. Any claim that metformin's benefit is AMPK-mediated has to answer this result. |
| 2004 | M | The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress SHW2004 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. |
Related entities
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