Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2 - PubMed
3 hours ago
- #Akt phosphorylation
- #structural biology
- #mTORC2
- mTOR forms two complexes: mTORC1 (nutrient-regulated) and mTORC2 (central to PI3K and Ras signaling, often dysregulated in cancer and diabetes).
- mTORC2 specifically phosphorylates Akt and PKC, not closely related kinases targeted by mTORC1, due to high substrate specificity.
- The study used semisynthetic probes to trap and determine the structure of the mTORC2::Akt complex, revealing recognition mechanisms.
- Unlike typical kinases that recognize local sequences near phosphorylation sites, mTORC2 uses secondary/tertiary structural elements of Akt.
- Specificity determinants are conserved structural elements in Akt that bind the mSin1 component of mTORC2, distal to the active site, and are found in at least 18 related substrates.
- Findings illuminate how mTORC2 recognizes canonical substrates and may guide the design of mTORC2-specific inhibitors.