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Mathematical simulations and experimental data revealed robust AKT phosphorylation (P-T308\/P-S473) after insulin stimulation, regardless of the intracellular AA levels. Conversely, AKT-mediated inhibitory TSC2 phosphorylation (P-T1462) substantially diminished during AA deprivation compared with AA treatment. Furthermore, we highlighted PP2A-mediated TSC2 dephosphorylation during AA removal, ensuring complete mTORC1 activation only upon concurrent AA and GF sensing. 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