What activates mTORC2?

GTPases can activate mTORC2 indirectly via PI3K. Ras-GTP, but not Ras-GDP, interacts with PI3K and increases its activity [91]. Rab35, another small GTPase, was identified in an shRNA screen as a regulator of growth factor-stimulated PI3K signaling [92], which then activates mTORC2.

How does mTOR regulate metabolism?

Activation of mTORC1 promotes protein synthesis, nucleotide synthesis, lipogenesis, glycolysis, and inhibits autophagy and lysosome biogenesis. Alternatively, mTORC2 regulates cell survival/glucose metabolism and cytoskeletal remodeling.

What does mTORC2 regulate in the cell?

mTOR Complex 2 (mTORC2) is an acutely rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodeling. The complex itself is rather large, consisting of seven protein subunits.

Where is mTORC2 located?

Subunits of mTORC2 were found to localize to several intracellular membrane compartments (Betz and Hall, 2013).

What is mTORC2?

Is mTORC2 a kinase?

The mammalian target of rapamycin (mTOR), a protein kinase, is the centre of huge attention due to its importance in intracellular signaling and in health and disease.

Does mTOR signaling influence the development of obesity?

Due to its central role in adapting metabolism to environmental conditions, mTOR signalling is also believed to be critical in the development of obesity.

Does rapamycin complex 2 (mTORC2) function in white adipose tissue (WAT)?

Here, we report that mechanistic target of rapamycin complex 2 (mTORC2) functions in white adipose tissue (WAT) to control expression of the lipogenic transcription factor ChREBPβ.

What is the relationship between mTOR and PI3K?

As mTOR is heavily linked to the PI3K pathway in terms of cancer progression and resistance to mTOR inhibitors, this prompted the development of dual PI3K/mTOR inhibitors, which target the p110⍺, β, and γ isoforms of PI3K in addition to the catalytic sites of mTORC1/2 [90].

How effective are mTOR inhibitors in cancer treatment?

Many mTOR inhibitors have only modest clinical activity and rapid development of resistance is common. Consequently clinical trials are largely shifting in favour combining mTOR inhibitors with conventional chemotherapy and radiotherapy to improve outcomes and circumvent resistance.