The conserved kinase mTOR (mechanistic target of rapamycin) regulates cell metabolism and promotes cell growth, proliferation, and survival in response to diverse environmental cues (e.g., nutrients; growth factors; hormones). mTOR forms the catalytic core of two multiprotein complexes, mTORC1 and mTORC2, which possess unique downstream targets and cellular functions. While mTORC1 and mTORC2 often respond to distinct upstream cues, they share a requirement for PI3K in their activation by growth factors. While many studies agree that amino acids activate mTORC1 but not mTORC2, several studies reported paradoxical activation of mTORC2 by amino acids. We noted that stimulating amino acid starved cells with a commercial mixture of amino acids increased mTORC2ādependent Akt S473 phosphorylation rapidly while reāfeeding cells with complete DMEM containing amino acids failed to do so. Interestingly, we found the pH of the commercial amino acid mixture to be ~ pH 10. Upon controlling for pH, stimulating starved cells with amino acids at pH 10 but not 7.4 increased mTORC2 signaling. Moreover, DMEM at alkaline pH was sufficient to increase mTORC2 catalytic activity and signaling. Using a fluorescent pHāsensitive dye (cSNARFā1āAM) coupled to ratioāmetric live cell imaging, we confirmed that alkaline extracellular pH (pHe) translated into a rapid increase in intracellular pH (pHi). Moreover, blunting this increase with a pharmacological inhibitor of an H+ transporter attenuated the increase in mTORC2 signaling by pHe. Alkaline pHi also activated AMPK, a canonical sensor of energetic stress that promotes mTORC2 signaling, as reported previously by us. Functionally, we found that alkaline pHi attenuated apoptosis caused by growth factor withdrawal through activation of AMPKāmTORC2 signaling. These results indicate that alkaline pHi augments mTORC2 signaling to promote cell survival, in part through AMPK. In the course of this work, we noted that pHi increased phosphorylation of several downstream targets of PI3K (e.g., Akt PāT308 and PāS473; S6K1 PāT389 and PāT229; PRAS40 PāT246; Tsc2 PāS939), suggesting that PI3K itself responds to changes in pHi. Indeed, alkaline pHi increased PIā3ā,4ā,5āāP3 levels in a manner sensitive to the PI3K inhibitor BYLā719. Thus, alkaline pHi elevates PI3K activity, which increases both mTORC1 and mTORC2 signaling. Mechanistically, we found that activation of PI3K by alkaline pHi induced dissociation of Tsc2 from lysosomal membranes, thereby relieving TSCāmediated suppression of Rheb, a mTORC1āactivating GTPase. Functionally, we found that activation of PI3K by alkaline pHi increased mTORC1āmediated 4EBP1 phosphorylation, which initiates capādependent translation by eIF4E. Alkaline pHi also increased mTORC1ādriven protein synthesis. Taken together, these findings reveal alkaline pHi as a previously unrecognized activator of PI3KāmTORC1/2 signaling that promotes protein synthesis and cell survival. As elevated pHi represents an underāappreciated hallmark of cancer cells, these findings suggest that by alkaline pHi sensing by the PI3KāmTOR axis and AMPKāmTORC2 axes may contribute to tumorigenesis.