Mechanistic target of rapamycin complex 1; Mechanistic target of rapamycin complex 2 (mTORC1; mTORC2)

The mechanistic target of rapamycin (mTOR) forms two evolutionary conserved, multisubunit kinase complexes known as **mTOR complex 1 (mTORC1)** and **mTOR complex 2 (mTORC2)**. Both complexes share mTOR as the core kinase subunit, but have distinct regulatory proteins and biological roles. - **mTORC1** is defined by the presence of Raptor, mLST8, PRAS40, and DEPTOR, among others, and primarily regulates cell growth, metabolism, protein synthesis, and autophagy in response to nutrients, growth factors, energy, and stress signals. - **mTORC2** is defined by Rictor, mSIN1, mLST8, Protor, and DEPTOR, and regulates cell survival, metabolism, proliferation, and cytoskeletal organization, largely via phosphorylation of AGC family protein kinases such as Akt (at Ser473), SGK, and PKC. Dysregulation of the mTOR pathway is implicated in diseases including **cancer, diabetes, neurodegeneration, and cardiovascular disorders**. **Rapamycin** and its analogs (rapalogs) selectively target mTORC1 and are approved for use in a range of indications including certain cancers and transplant rejection, while newer inhibitors that target both mTORC1 and mTORC2 are under clinical investigation for broader therapeutic benefit[1][3][4][7].

Other names

mTOR complex 1 (mTORC1)mTOR complex 2 (mTORC2)Mammalian target of rapamycin complex 1Mammalian target of rapamycin complex 2Raptor-mTOR complex (for mTORC1)Rictor-mTOR complex (for mTORC2)

Allosteric inhibition (e.g., rapamycin-FKBP12 binds and inhibits mTORC1) - ATP-competitive inhibition (small molecules that target kinase domain and inhibit both mTORC1/mTORC2) - Inhibition of phosphorylation of downstream effectors (e.g., S6K1 for mTORC1, Akt Ser473 for mTORC2)