[6] The complex also plays a role as an important regulator in the organization of the actin cytoskeleton through its stimulation of F-actin stress fibers, paxillin, RhoA, Rac1, Cdc42, and protein kinase C α (PKCα).
Some findings based on its activity point to cellular endomembranes, such as of mitochondria, as a possible site of mTORC2,[6] whereas other suggest that the complex could be additionally located at the plasma membrane; however, this may be due to its association with Akt.
[16] It is not clear if these membranes display mTORC2 activity in the cellular context, or if these pools contribute to phosphorylation of mTORC2 substrates.
[22] Originally, mTORC2 was identified as a rapamycin-insensitive entity, as acute exposure to rapamycin did not affect mTORC2 activity or Akt phosphorylation.
[30][31][32] mTORC2 controls cell survival and proliferation mainly through phosphorylation of several members of the AGC (PKA/PKG/PKC) protein kinase family.
mTORC2 regulates actin cytoskeleton through PKCα [33] but is able to phosphorylate other members of the PKC family that have various regulatory functions in cell migration and cytoskeletal remodeling.
[39] In many types of human cancer, hyperactivation of mTORC2 caused by mutations and aberrant amplifications of mTORC2 core components is frequently observed.
[46] Chronic mTORC2 activity may play a role in systemic lupus erythematosus by impairing lysosome function.
[47] Studies using mice with tissue-specific loss of Rictor, and thus inactive mTORC2, have found that mTORC2 plays a critical role in the regulation of glucose homeostasis.
[54] The role of mTORC2 in skeletal muscle has taken time to uncover, but genetic loss of mTORC2/Rictor in skeletal muscle results in decreased insulin-stimulated glucose uptake, and resistance to the effects of an mTOR kinase inhibitor on insulin resistance, highlighting a critical role for mTOR in the regulation of glucose homeostasis in this tissue.