Alkaline intracellular pH (pHi) activates AMPK-mTORC2 signaling to promote cell survival during growth factor limitation.

ABSTRACT: The mechanistic target of rapamycin (mTOR) complex 2 (mTORC2) signaling controls cell metabolism, promotes cell survival, and contributes to tumorigenesis, yet its upstream regulation remains poorly defined. Although considerable evidence supports the prevailing view that amino acids activate mTOR complex 1 but not mTORC2, several studies reported paradoxical activation of mTORC2 signaling by amino acids. We noted that after amino acid starvation of cells in culture, addition of an amino acid solution increased mTORC2 signaling. Interestingly, we found the pH of the amino acid solution to be alkaline, ∼pH 10. These observations led us to discover and demonstrate here that alkaline intracellular pH (pHi) represents a previously unknown activator of mTORC2. Using a fluorescent pH-sensitive d

SUBMITTER: Kazyken D 

PROVIDER: S-EPMC8479482 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature