Fig 1: Dynamic mTOR model.(A) Scheme summarizing the mTOR pathway. Amino acids directly activate mTORC1, which targets PRAS40-pS183, p70-S6K-pT389, and 4E-BP1-pT37/46. The insulin signal is transduced via the IR. The IR phosphorylates and recruits IRS1 which in turn recruits and activates PI3K. PI3K promotes the translocation of PDK1 to the membrane, where PDK1 phosphorylates Akt-pT308. Akt phosphorylates and inhibits the endogenous mTORC1 inhibitors PRAS40 at T246 and TSC2 at T1462. Thus, Akt activates mTORC1. p70-S6K inhibits IRS1 by direct phosphorylation at S636/639. PI3K also activates mTORC2, which targets Akt-pS473. In this study, we show that upon stress, mTORC1 is activated via the PI3K axis to promote stress granule assembly. (B) Topology of model I without stress input (Supplemental Data 1). Brown squares = species included in the model, circles = species variants (P, phosphorylation at the indicated site; cyt, cytosolic localization; mem, cell membrane localization; and *, active state), dark brown = observable species, species in ellipses = possible inputs to the model (insulin and amino acids) and inhibitory agents (MK-2206 and wortmannin), dark blue lines = mTORC2 activity, and light blue lines = mTORC1 activity. (C) Wortmannin fully inhibits PI3K (100%) in MCF-7 cells upon arsenite treatment. Akt-T308 phosphorylation (data shown in Fig S3A) was used to calculate the extent of PI3K inhibition upon wortmannin treatment. A one-way ANOVA was used to calculate P-values of Akt-T308 phosphorylation upon arsenite and arsenite + wortmannin treatment. As under wortmannin treatment, there was no significant induction of Akt-pT308 (P = 0.3226); the extent of inhibition for wortmannin was set to 100%. (D) MK-2206 partially inhibits Akt (83%) in MCF-7 cells upon arsenite treatment. TSC2-T1462 phosphorylation (data shown in Fig S3C) was used as to calculate the extent of Akt inhibition upon MK-2206 treatment. A one-way ANOVA was used to calculate P-values of TSC2-1462 phosphorylation upon arsenite treatment and arsenite + MK-2206 treatment. As under MK-2206 treatment, there was still a significant induction of TSC2-pT1462 (P = 0.0239), the extent of inhibition for MK-2206 was calculated by comparing the slopes of induction curves (83%) between carrier and MK-2206 treatment (indicated as red lines). (E) Summary of the extent of inhibition for wortmannin and MK-2206 in MCF-7 cells under arsenite treatment.