Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome
What this study shows
Asked why two inherited tumour syndromes, tuberous sclerosis and Peutz-Jeghers syndrome, look so alike under the microscope. Re-expressing LKB1 in LKB1-null HeLa cells raised AMPK activation-loop phosphorylation and lowered phosphorylation of S6K and 4E-BP1, while knocking LKB1 down did the opposite. The effect on mTOR outputs needed both AMPK and TSC2, placing LKB1 upstream of the TSC2-mTOR axis through AMPK. Together with Shaw et al. 2004 this is one of the two papers that tied energy stress, via LKB1 and AMPK, to TSC2. Boundary: cultured cell lines with overexpression and knockdown; the tumour-syndrome link is an interpretation, not a test in patients.
At a glance
| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: HeLa (LKB1-null) and HEK293 cells; Lkb1-null mouse embryonic fibroblasts; RNAi) 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 | HeLa (LKB1-null) and HEK293 cells; Lkb1-null mouse embryonic fibroblasts; RNAi |
| Journal | Genes & Development |
| Year | 2004 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1101/gad.1199104 · PMID 15231735 · Free full text (PMC443516) |
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 re-expression and RNAi knockdown; AMPK and TSC2 dependence |
| Target | LKB1 -> AMPK -> TSC2 -> mTORC1 |
| Model | Human cell lines (HeLa, HEK293), mouse embryonic fibroblasts |
| Effect | LKB1 activates AMPK and, through TSC2, lowers mTORC1 signalling to S6K and 4E-BP1 |
In the Atlas
Related topics
Links in the pathway map
- Supports LKB1 (STK11) activates AMPK
More studies on this topic
- ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS (2010)
- The LKB1 tumor suppressor negatively regulates mTOR signaling (2004)
- Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state (2010)
- The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress (2004)
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