Thr2446Is a Novel Mammalian Target of Rapamycin (mTOR) Phosphorylation Site Regulated by Nutrient Status

摘要: The mammalian target of rapamycin (mTOR) is a key regulator protein translation. Signaling via mTOR increased by growth factors but decreased during nutrient deprivation. Previous studies have identified Ser2448 as nutrient-regulated phosphorylation site located in the catalytic domain, insulin stimulates kinase B (PKB), while attenuated with amino acid starvation. Here we Thr2446 novel on mTOR. becomes phosphorylated when CHO-IR cells are nutrient-deprived, reduced stimulation. Nutrient deprivation activates AMP-activated (AMPK). To test whether this could be involved regulating phoshorylation mTOR, treated cultured murine myotubes 5′-aminoimidazole-4-carboxamide ribonucleoside (AICAR) or dinitrophenol (DNP). Both treatments activated AMPK and also caused concomitant increase parallel decrease insulin's ability to phosphorylate p70 S6 kinase. In vitro assays using peptides based sequence acids 2440–2551 found that PKB capable phosphorylating sites region. However, restricted mutated an acidic residue mimicking phosphorylation. Conversely, AMP-kinase-induced phosphorylated. These data suggest differential act switch mechanism integrate signals from status control regulation