Pathway link MET-PKM2

Methionine – PKM2

Methionine binds PKM2.

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.

Free methionine binds PKM2 in a recognition pocket separate from its catalytic site. Binding does not inhibit PKM2 as an enzyme: the sensing works independently of its glycolytic activity. What changes is PKM2's interaction with GATOR2: when methionine is present, PKM2 stops restraining GATOR2 (the restraining step is the separate PKM2-GATOR2 edge), so methionine switches that brake off. The binding was captured in living human cells with a photoaffinity methionine analogue and confirmed biochemically. This reads methionine itself, unlike SAMTOR, which reads the metabolite SAM.

The conditions it 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.

Time it takes

seconds

Step

direct (one molecule acts on the other)

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

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.

“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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