Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB

January 29, 2021 / Cutting edges

It has been thought that Sirolimus (rapamycin) inhibits mTORC1 but not mTORC2 activity. FKBP12-rapamycin complex binds to FRB domain of mTOR and inhibits kinase activity of mTOR. Rictor, a major component of mTORC2 binds mTOR and covers FRB domain, thus FKBP12-rapamycin can not access mTORC2. This is the reason that rapamycin is not effective to mTORC2. However, FKBP12-rapamycin can bind to newly synthesized “naked” mTOR. Therefore, prolonged treatment with rapamycin inhibits mTORC2, as well as mTORC1. Since mTORC2 is involved in the regulation of cell shape and survival, application of rapamycin might expand.

References

Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.
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