Weighing In on mTOR Complex 2 Signaling: The Expanding Role in Cell Metabolism

Figure 3

mTORC2 in cell metabolism. (a) mTORC2 promotes glucose metabolism via glycolysis and PPP (pentose phosphate pathway). In response to growth factors, mTORC2 activates glucose catabolism through two main factors, Akt and c-Myc. Akt activates glycolysis at both transcriptional and posttranslational levels. c-Myc enhances the expression of genes involved in glycolysis and PPP. Activated factors are shown in red letters; suppressed factors are shown in blue. Solid line indicates direct regulation; dash line indicates indirect regulation. (b) mTORC2 promotes lipogenesis via Akt-dependent and -independent mechanisms. mTORC2 activates, via Akt, SREBP and ChREBP, two transcription factors for the expression of lipogenic genes, such as ACLY, ACC, FAS, and SCD1. mTORC2 may also stimulate lipogenesis by activating mTORC1 in an Akt-independent manner. (c) mTORC2 regulates amino acids and nucleotide metabolism. mTORC2 regulates amino acid transport by modulating activity of amino acid transporters, SLC7A5 and SLC38A2, and antiporter, xCT. In addition, mTORC2 activates glutamine transporters, SLC1A5 and SLC38A5, via c-Myc to promote glutamine uptake. By activating glycolysis, mTORC2 increases the production of 3-phospholycerate and pyruvate, which can be used to synthesize serine and alanine. mTORC2 promotes glutaminolysis via c-Myc, which transforms glutamine to glutamate and aspartate. Purine synthesis can be stimulated by mTORC2 through Akt-mediated activation of transketolase. Description of the abbreviations listed is contained within this review.

(a)

(b)

(c)