Longevity & AgingScientists Crack How mTORC2 Selectively Activates Akt in a Longevity Pathway
Researchers used semisynthetic chemical probes and cryo-electron microscopy to trap and visualize the mTORC2–Akt complex for the first time. Unlike most kinases that recognize short amino acid sequences near the phosphorylation site, mTORC2 reads the three-dimensional shape of Akt, engaging structural elements on the mSin1 subunit roughly 75 Å from the catalytic site. This mechanism explains how mTORC2 selectively phosphorylates Akt, PKC, and SGK1 while ignoring closely related kinases, and opens a path toward designing mTORC2-specific inhibitors with potential in cancer, diabetes, and aging-related diseases.
