Oliver's mTOR Atlas Evidence Platform
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Pathway link AKT-FOXO

Akt/PKB FOXO1/3

Akt/PKB inhibits FOXO1/3.

Akt tags FOXO proteins and keeps them out of the nucleus; this specific link belongs to mTORC2, not mTORC1.

Akt phosphorylates FOXO transcription factors and excludes them from the nucleus. Rictor or mLST8 deletion abolishes signalling to Akt–FOXO while sparing S6K1.

The conditions it holds under

Mouse knockouts and cell lines; FOXO isoform contributions differ by tissue.

This Akt output depends on mTORC2. Deleting rictor or mLST8 in mice removed Akt signalling to FOXO while S6K1 was spared (GUE2006), and SIN1, an essential mTORC2 subunit, controls Akt Ser473 phosphorylation and which substrates Akt reaches (JAC2006). The mTORC2-to-Akt step itself is the separate edge MTORC2-AKT.

Time it takes
minutes
Step
direct (one molecule acts on the other)
Measured in
mouse, mammalian cells
Where in the cell
nucleus
Reaches people?
plausible in people, not shown directly
How settled
settled in the literature

Studies behind it

YearEvidenceStudy
2006 M Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1GUE2006 The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice.
2006 M SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificityJAC2006 SIN1 maintains rictor-mTOR integrity and confers mTORC2 Akt-Ser473 kinase activity and substrate specificity.
1999 M Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factorBRU1999 Akt phosphorylates the Forkhead transcription factor FKHRL1 (a FOXO family member), driving its cytoplasmic retention via 14-3-3 binding and blocking Fas-ligand-driven apoptosis — the discovery that placed FOXO transcription factors downstream of Akt/PI3K survival signalling.

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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