PKM2
Pyruvate kinase M2, best known as a glycolytic enzyme. A single 2026 study (SANG2026, human cells, photoaffinity methionine probe and chemoproteomics) reports that PKM2 also binds free methionine through a pocket separate from its catalytic site and relays methionine availability to mTORC1 through the GATOR2 complex, independently of its enzyme activity. Not yet replicated, and its importance in whole animals is untested.
A sugar-burning enzyme that may double as a methionine detector. A sugar-burning enzyme that, according to one recent study in human cells, also works as a methionine detector for mTORC1. Nobody has repeated that result yet, and it has not been tested in animals.
SANG2026 (photoaffinity chemoproteomics, human cells): methionine binds a pocket separate from the catalytic site, sensing independent of enzyme activity, signal relayed via GATOR2. Single study, not replicated; whole-organism relevance untested.
TL;DR. PKM2 appears in 1 curated study in Oliver's mTOR Atlas: 1 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| PKM2 inhibits GATOR2 mechanism: binding · this link in full · on the map table | Without methionine, PKM2 holds GATOR2 back, so mTORC1 stays off. 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. plausible in people, not shown directly · emerging, few independent studies | M | SANG2026 |
| Methionine binds PKM2 mechanism: binding · this link in full · on the map table | Methionine sticks to PKM2. This does not switch the enzyme off; it just stops PKM2 from holding the brake on GATOR2. A second methionine detector next to SAMTOR. Holds under: One study in cultured human cells (SANG2026): photoaffinity chemoproteomics plus biochemical validation. No affinity measurement in tissue, no animal or human test, and not yet replicated by another group. The direction (methionine binding relieves PKM2's restraint on GATOR2) is taken from the authors' abstract; the full text was not accessible when this link was written. Parallel to, not a replacement for, SAM sensing by SAMTOR (SAM-SAMTOR): the two sensors read different molecules and act on different complexes (PKM2 on GATOR2, SAMTOR on GATOR1-KICSTOR). How much each contributes when methionine is restricted in a whole animal is untested. plausible in people, not shown directly · emerging, few independent studies | M | SANG2026 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| 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 | M | "Trojan" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway SANG2026 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. |
Related entities
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