Oliver's mTOR Atlas Evidence Platform
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Pathway link PKM2-GATOR2

PKM2 GATOR2

PKM2 inhibits GATOR2.

Without methionine, PKM2 holds GATOR2 back, so mTORC1 stays off.

When methionine is scarce, PKM2 interacts with the GATOR2 complex and keeps it from relaying the 'nutrients present' signal, so mTORC1 stays off. The authors propose that stabilising the PKM2-GATOR2 interaction would mimic methionine starvation. Same double-negative logic as Sestrin2 for leucine and CASTOR1 for arginine.

The conditions it holds under

One study in cultured human cells (SANG2026). Whether PKM2 binds GATOR2 directly or through another protein, and on which subunit, is not stated in the abstract, so the step is marked unresolved. Cell and chemoproteomic data do not show that this sensor matters for mTORC1 in a whole organism. Not yet replicated.

The methionine route via PKM2 converges on GATOR2, the same complex read by Sestrin2 (leucine) and CASTOR1 (arginine); the SAM route via SAMTOR acts one step further on, at GATOR1-KICSTOR.

Time it takes
minutes
Step
not yet resolved
Measured in
human cells
Where in the cell
cytosol
Reaches people?
plausible in people, not shown directly
How settled
emerging, few independent studies

Studies behind it

YearEvidenceStudy
2026 M "Trojan" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 PathwaySANG2026 Identifies PKM2 as a direct methionine sensor for mTORC1. A photoaffinity methionine analogue plus chemoproteomics showed that PKM2 binds free methionine through a distinct recognition pocket — independently of its glycolytic enzyme activity — and transduces methionine availability to mTORC1 via the GATOR2 complex. Complements SAMTOR (GU2017), which reads the methionine metabolite SAM rather than methionine itself, and suggests a route to a pharmacological "methionine pseudostarvation" state.

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.

“Inhibits” describes the effect on the target's activity, not on how much of it there is.

“How settled” describes how far researchers in the field agree. It is not the same as the sign-off above, which only says whether a named curator has checked this page.

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