Oliver's mTOR Atlas Evidence Platform
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Pathway link GATOR2-GATOR1

GATOR2 GATOR1

GATOR2 inhibits GATOR1.

Everyone agrees GATOR2 holds GATOR1 back when amino acids are around. Exactly how it does it is not settled by the work this Atlas holds, and the gap is left visible on purpose.

Released GATOR2 suppresses GATOR1 - a double negative. Two brakes in series is why the sensors can flip mTORC1 on so sharply.

The conditions it holds under

The epistasis is solid. VAL2022 resolved GATOR2's architecture by cryo-EM - a 1.1 MDa cage - and mapped where the sensors dock, but exactly how GATOR2 suppresses GATOR1's GAP activity is still not settled.

Time it takes
seconds
Step
direct (one molecule acts on the other)
Measured in
human cells
Where in the cell
lysosome
Reaches people?
plausible in people, not shown directly
How settled
emerging, few independent studies

Studies behind it

YearEvidenceStudy
2013 M A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1BAR2013 Found the OFF switch for amino acid signaling: the GATOR1 complex is a GAP that shuts the Rag GTPases (and thus mTORC1) down when amino acids run low, while GATOR2 opposes it. GATOR1 genes are mutated in cancers, making those tumors 'blind' to starvation and hypersensitive to rapamycin.
2014 M Sestrins inhibit mTORC1 kinase activation through the GATOR complexPAR2014 Sestrins inhibit mTORC1 activation through the GATOR2 complex.
2022 M Structure of the nutrient-sensing hub GATOR2VAL2022 Cryo-EM structure of human GATOR2: a 1.1 MDa, two-fold symmetric cage built on an octagonal scaffold decorated with eight pairs of WD40 beta-propellers, and a map of where Sestrin2 and CASTOR1 dock. It substantially advances the GATOR2 side of the sensor module, though how GATOR2 inhibits GATOR1 is still not fully settled.

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.

If this link rests on your own work: a click on “This looks right” below, or a short note through “Report an error”, helps us more than anything else on this page.

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