![]() In addition to 4EBP1, mTOR also regulates translation via S6 kinase (S6K, formerly known as p70 s6K). Phosphorylation of 4EBP1 releases eIF4E, allowing initiation of translation ( Gingras et al., 2004). mTOR exerts its effects by phosphorylating eukaryotic initiation factor 4E binding protein 1 (4EBP1), which inhibits 5′-cap-dependent mRNA translation (the majority of cellular translation) by binding and inactivating eIF4E. TORC1 and possibly TORC2 are conserved from yeast to man.Central to the pathways that induce cell growth in mammals is the murine target of rapamycin (mTOR), a multi-domain, 298 kDa, evolutionarily-conserved Ser/Thr kinase that is inhibited by the drug rapamycin ( Schmelzle and Hall, 2000). Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. FKBP-rapamycin fails to bind TORC2, and TORC2 disruption causes an actin defect, suggesting that TORC2 mediates the rapamycin-insensitive, TOR2-unique pathway. FKBP-rapamycin binds TORC1, and TORC1 disruption mimics rapamycin treatment, suggesting that TORC1 mediates the rapamycin-sensitive, TOR-shared pathway. TOR Complex 1 (TORC1) contains TOR1 or TOR2, KOG1 (YHR186c), and LST8. We describe two functionally distinct TOR complexes. TOR2 additionally regulates polarization of the actin cytoskeleton in a rapamycin-insensitive manner. The target of rapamycin (TOR) proteins in Saccharomyces cerevisiae, TOR1 and TOR2, redundantly regulate growth in a rapamycin-sensitive manner.
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