AKT (Protein Kinase B)

Classification

Category: Upstream regulator AND mTORC2 substrate (dual role)

Aliases: PKB, AKT1/AKT2/AKT3

Relationship to mTOR complexes: Upstream of mTORC1 (via TSC1/2); downstream substrate of mTORC2 (Ser473) — see mTORC1 vs mTORC2 for the full complex-level map.

Summary

AKT plays a dual role in this pathway map. As part of the insulin/IGF-1-PI3K-AKT axis, active AKT phosphorylates and INHIBITS TSC2, relieving the brake on Rheb and thereby ACTIVATING mTORC1 (upstream role). Separately, mTORC2 phosphorylates AKT at Ser473, a step required for AKT's full activation (downstream/substrate role). AKT therefore sits both upstream of mTORC1 and downstream of mTORC2.

• Insulin/IGF-1 -> PI3K signaling activates AKT (upstream-role input)
• mTORC2 phosphorylates AKT at Ser473, required for full AKT activation (downstream-role input) -- see /mtorc1-vs-mtorc2

• Phosphorylates and inhibits TSC2, activating Rheb/mTORC1 (upstream-role output)
• Once fully active (via mTORC2's Ser473 phosphorylation), AKT phosphorylates numerous additional substrates in metabolism, survival, and growth signaling beyond the scope of this mTOR-focused dataset

• AKT is the clearest example in this pathway map of why mTORC1 and mTORC2 must not be treated as a single 'mTOR' signal: AKT is activated BY insulin/IGF-1/PI3K signaling and in turn activates mTORC1, while simultaneously being a direct phosphorylation TARGET (Ser473) of the separate mTORC2 complex.
• p-AKT (Ser473) is the assay marker this dataset's pathway/assay-reference table designates as 'the' mTORC2 activity marker.

Source tier

Tier 2 · Biological synthesis (author-cluster reviews, not primary trial data) Reference synthesis attributed in the brief to the Saxton & Sabatini; Laplante & Sabatini; and Liu & Sabatini mTOR review literature (author-cluster attribution, tier 2, brief §4). Exact article-level PMID/DOI not supplied in the sourcing brief and is not fabricated here.