Technical Overview
mTOR (mammalian Target of Rapamycin) was originally identified in Saccharomyces cerevisiae where mutations of the protein kinase, TOR, confer rapamycin resistance. mTOR is a large (>250 kDa) class IV PI-3 kinase family member with protein kinase activity, but lacks any lipid kinase activity. mTOR forms a complex with the 12 kDa cytosolic protein, FKBP-12 and rapamycin that functions to arrest the cell cycle in the G1 phase. Cell cycle arrest by the mTOR complex requires the presence of the intact kinase domain of mTOR and, in particular, a conserved serine within this domain, Ser2448, which has been identified as an Akt/PKB-mediated phosphorylation site. Biomarkers indicate that the mTOR pathway is hyperactive in certain types of cancers, suggesting that mTOR could be an attractive target for cancer therapy. Activated mTOR may provide tumor cells with a growth advantage by promoting protein synthesis, which is the best-described physiological function of mTOR signaling. mTOR regulates Akt activity, a crucial downstream effector in the PI-3K–PTEN pathway, which controls cell proliferation and survival. Targeting this function of mTOR may also have therapeutic potential. |
