Mammalian target of rapamycin complex 2 (mTORC2) has been implicated in cancer by regulating multiple AGC kinases, especially AKT proteins. In the liver, AKT1 and AKT2 are widely expressed.

Jan 29, 2020 · Here the authors report that a mTORC2-Akt axis specifically activates ACLY to promote lipid synthesis and histone acetylation during brown adipocyte differentiation.

Jan 5, 2023 · mTORC2 regulates autophagy by phosphorylating AGC kinases (AKT, PKC, and SGK1). The mTORC2/PKC axis promotes autophagosome precursor formation by regulating Atg16; the mTORC2/AKT axis inhibits autophagy by regulating FOXO3 and LAMP-2A; the mTORC2/SGK1 axis inhibits autophagy by regulating mitochondrial homeostasis, FOXO3 and …

Apr 13, 2021 · Overexpression of PDK1 in mTORC2-deficient cells rescued hydrophobic motif phosphorylation of PKC and Akt by a mechanism dependent on their intrinsic catalytic activity, revealing that mTORC2 facilitates the PDK1 phosphorylation step, which, in turn, enables autophosphorylation.

Jul 1, 2019 · Using biochemical reconstitution with purified proteins, we demonstrate that Rho–GDP promotes AKT phosphorylation by assembling a supercomplex with Ras–GTP and mTORC2. This supercomplex...

Jan 29, 2020 · mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss.

In growing/proliferating cells, mTORC1 promotes the synthesis of macromolecules (e.g. lipids, proteins, and nucleotides), while in metabolic tissues like the liver, mTORC1 facilitates nutrient storage while inhibiting catabolic metabolism (e.g. autophagy). mTORC2 phosphorylates and activates Akt and other kinases of the AGC superfamily to ...

Dec 22, 2023 · NUAK1 interacts with mTORC2 components and regulates mTORC2-dependent activation of Akt by controlling lysosome positioning and mTOR association with this organelle. A second mechanism involves NUAK1 directly phosphorylating Akt at Ser-473.

Jun 4, 2013 · We demonstrate that by phosphorylating mTORC2 on SIN1 T86, Akt enhances the activity of mTORC2, which in turn results in increased feedback phosphorylation onto Akt (Figure 6H). This model unifies the growth factor-dependent activation of Akt with that of mTORC2 through an Akt-dependent positive feedback process, providing a more complete ...

Aug 11, 2015 · The mechanistic target of rapamycin complex 2 (mTORC2) responds to growth factors through a poorly defined mechanism that requires PI3K. Yang et al. reveal that Akt phosphorylates SIN1, a key component of mTORC2, at Threonine 86, in diverse cells and conditions, enhancing mTORC2 activity.