Complexo mTORC2 é ativado por aminoácidos pela via PI3K/Akt.

The activity of mammalian target of rapamycin (mTOR) complexes regulates essential cellular processes, such as growth, proliferation or survival. Nutrients such as amino acids are important regulators of mTOR Complex 1 (mTORC1) activation, thus affecting cell growth, protein synthesis and autophagy. Here, we show that amino acids may also activate mTOR Complex 2 (mTORC2). This activation is mediated by the activity of class I PI3K and of Akt. Amino acids induced a rapid phosphorylation of Akt at Thr308 and Ser473. Whereas both phosphorylations were dependent on the presence of mTOR, only Akt phosphorylation at Ser473 was dependent on the presence of rictor, a specific component of mTORC2. Kinase assays confirmed mTORC2 activation by amino acids. This signaling was functional, as demonstrated by the phosphorylation of Akt substrate FOXO3a. Interestingly, using different starvation conditions, amino acids can selectively activate mTORC1 or mTORC2. These findings identify a new signaling pathway used by amino acids underscoring the crucial importance of these nutrients in cell metabolism and offering new mechanistic insights.