GSK3 and its interactions with the PI3K/AKT/mTOR signalling network.
Level 5 - mechanism / opinion, no new human data
Narrative review of molecular signaling mechanisms without primary empirical human data.
PubMed 28712664 · doi:10.1016/j.jbior.2017.06.003
What was done
This narrative review summarizes molecular mechanisms governing Glycogen Synthase Kinase-3 (GSK3) activity and its bidirectional interactions with the PI3K/AKT/mTOR signaling network, focusing on feedback regulation and priming phosphorylation requirements.
What was found
The abstract reports no numerical or quantitative findings. It describes that AKT inhibits GSK3 via an autoinhibitory pseudosubstrate sequence, while GSK3 can phosphorylate multiple components of the network (including AKT, RICTOR, TSC1/2, PTEN, and IRS1/2) to exert feedback control. It notes that insulated pools of GSK3 exist that are not regulated by PI3K/AKT inputs (such as for beta-catenin) and that GSK3 predominantly acts as an amplifier of electrostatic effects following substrate-specific priming phosphorylation four amino acids C-terminal to its target sites.
Why it matters
It provides a mechanistic framework for understanding how GSK3 regulates metabolic and oncogenic signaling pathways through compartmentalized pools rather than a single uniform response.
Limits
The paper is a non-systematic narrative review containing no primary experimental data, quantitative metrics, or clinical outcomes. Specific experimental models and study selection criteria are not described in the abstract.
Cited by
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