Mechanistic target of rapamycin complex 2 (mTORC2) (mTORC2)

The mechanistic target of rapamycin complex 2 (mTORC2) is a multi-protein signaling hub centered around the mTOR serine/threonine kinase (UniProt: P42345). It is uniquely defined by the presence of the RICTOR subunit (UniProt: Q6R327), which serves as a scaffold for the complex and distinguishes it from the rapamycin-sensitive mTORC1 (PubMed: 15467732). mTORC2 functions as a key regulator of the actin cytoskeleton and mediates cell survival, growth, and metabolism by phosphorylating several members of the AGC kinase family, including AKT at Ser473, SGK1, and PKC alpha (StatPearls: NBK537199). In the context of human disease, mTORC2 is frequently hyperactivated in various cancers, where it promotes tumor progression and confers resistance to standard therapies (Wikipedia: mTORC2). While acute treatment with rapamycin does not inhibit mTORC2, second-generation ATP-competitive inhibitors like Sapanisertib have been developed to target the kinase domain of both mTOR complexes to provide more robust pathway suppression (PubMed: 29686383).

Other names

Mammalian target of rapamycin complex 2RICTOR-mTOR complexmTOR-RICTOR complex

ATP-competitive inhibition of the mTOR catalytic domain, resulting in the simultaneous suppression of both mTORC1 and mTORC2 signaling pathways (PubMed: 29686383).