Structural and mechanistic basis of mTORC2 activation of protein kinase AKT/PKB - PubMed
5 hours ago
- #mTORC2
- #cancer therapy
- #AKT/PKB
- The PI3K/AKT/mTOR signaling pathway regulates cellular processes like growth, survival, metabolism, and protein synthesis.
- Dysregulation of this pathway is linked to diseases such as cancer, driving uncontrolled cell proliferation.
- mTOR forms two complexes: mTORC1 (nutrient-regulated, controls protein synthesis and autophagy) and mTORC2 (central in PI3K/Ras signaling, often disrupted in cancer and diabetes).
- AKT is phosphorylated by PDK1 and mTORC2, enabling regulation of various cellular functions.
- mTORC2 selectively phosphorylates AKT and PKC due to structural interactions with the mSin1 subunit, showing high substrate specificity.
- Recent studies using semisynthetic probes reveal structural elements in AKT that interact with mSin1, aiding in the design of mTORC2-specific inhibitors.
- Targeting the AKT/mTOR axis holds therapeutic promise, especially in cancer, but challenges remain due to complex regulation and feedback mechanisms.
- Emerging combination therapies show potential in overcoming these challenges.