Pathway link AKT-TSC
Akt/PKB TSC1/TSC2
Akt/PKB inhibits TSC1/TSC2.
Akt tags TSC2 to disable it. Growth signals work by releasing a brake, not by pressing a gas pedal.
The conditions it holds under
In mouse liver, Akt phosphorylation of TSC2 is the main route by which insulin switches on mTORC1, but feeding activates hepatic mTORC1 without it; that response needs dietary protein instead (KAL2026). The biochemical mechanism itself was shown in cultured human cells (INO2002).
- Time it takes
- seconds
- 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 |
|---|---|---|
| 2002 | M | TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signallingINO2002 Akt directly phosphorylates and inactivates TSC2, disrupting the TSC1-TSC2 complex and releasing its inhibition of mTOR - the link between growth-factor/insulin signaling and mTORC1 activation. |
| 2026 | A | Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.KAL2026 In liver-specific mouse genetic models, AKT-mediated TSC2 phosphorylation is the main route by which insulin induces hepatic mTORC1, but is dispensable for feeding-induced activation; postprandial mTORC1 activation instead requires dietary protein, and hepatic mTORC1 signalling is not elevated in diet-induced obesity despite impaired insulin/glucose homeostasis. |
| 2026 | A | Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle SizeLAP2026 Using a mouse model expressing an AKT-nonphosphorylatable TSC2 mutant specifically in skeletal muscle, the Manning lab genetically separated feeding-induced from contraction-induced mTORC1 activation. AKT-mediated TSC2 phosphorylation is required for feeding (but not contraction) to activate muscle mTORC1 and drive postprandial protein synthesis — yet mice lacking this feeding-induced signal have normal muscle mass and myofiber size, and instead show improved maximal endurance capacity with a modest rise in mitochondrial content. The finding dissociates mTORC1's role in postprandial anabolism from its role in maintaining steady-state muscle mass, and is a directly relevant data point for whether the pattern/source of mTORC1 activation (feeding vs. mechanical) — not just its average level — shapes downstream outcomes. |
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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