Pathway link AMPK-TSC
AMPK TSC1/TSC2
AMPK activates TSC1/TSC2.
When energy is low, AMPK tags TSC2 and makes the brake on Rheb stronger.
The conditions it holds under
Mammalian cell biochemistry (INO2003, INO2006). Not tested in whole animals or in people by the cited studies.
Relative weight of this arm is cell-type dependent. AMPK reaches mTORC1 two ways – activating TSC2 and directly phosphorylating Raptor – and TSC2-null cells still suppress mTORC1 under energy stress, so the TSC2 arm is not universally the dominant one. Which arm carries the signal depends on TSC status, LKB1 status and the severity and duration of the energy stress.
- Time it takes
- minutes
- Step
- direct (one molecule acts on the other)
- Measured in
- mammalian cells
- Where in the cell
- cytosol
- Reaches people?
- plausible in people, not shown directly
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2003 | M | TSC2 mediates cellular energy response to control cell growth and survivalINO2003 Established the energy-sensing arm of the pathway. When energy runs low, AMPK phosphorylates TSC2, boosting its ability to shut mTOR down - protecting the cell from burning through resources and from starvation-induced death. One of the founding papers for how mTOR reads the cell's fuel gauge (complements the Akt-TSC2 growth-factor arm). |
| 2006 | M | TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growthINO2006 TSC2 integrates Wnt and energy signals through coordinated AMPK and GSK3 phosphorylation. |
| 2008 | M | p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signalingBUD2008 Connected DNA damage to mTOR. Two p53 target genes, Sestrin1 and Sestrin2, bound and activated AMPK and steered it to phosphorylate TSC2, which raised TSC2 GAP activity and lowered mTOR signalling. Sesn2-deficient mice failed to inhibit mTOR signalling after genotoxic challenge. This describes the stress-induced arm of Sestrin biology; the later leucine-sensing role of Sestrin2 through GATOR2 is a separate mechanism. Boundary: cell lines and mice under acute genotoxic stress; no human data. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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