The mTORC2 signaling network: targets and cross-talks The mechanistic target of rapamycin (mTOR) controls cell metabolism in response to growth signals and stress. mTOR functions through two complexes, mTORC1 and mTORC2. While mTORC1 is inhibited by rapamycin, mTORC2 is not. mTORC2 is activated by anabolic signals and stress and mediates signals from growth factor and G-protein coupled receptors. It regulates Akt, PKC, and SGK, which are members of the AGC kinase family. mTORC2 is regulated by cellular stimuli, including compartmentalization and modulation of its components. Phosphorylation of its substrates, particularly AGC kinases, mediates its functions in growth, proliferation, survival, and differentiation. mTORC2 also interacts with other signaling and metabolic components, and its activity is crucial for metabolic reprogramming and cell survival. The review discusses the regulation and targets of mTORC2, how it intersects with other pathways, and how to target mTORC2 for disease treatment. mTORC2 is composed of mTOR, rictor, and SIN1. It is a dimer of multi-subunit complexes and has a rhombus-like shape. mTOR is a PI3K-related kinase with specific domains that modulate its function. mTORC2 is regulated by post-translational modifications, including phosphorylation, acetylation, ubiquitination, and malonylation. These modifications affect mTORC2's expression, localization, and activity. mTORC2 also interacts with other proteins such as DEPTOR, Sestrin2, and Protor, which modulate its activity. The expression of mTORC2 components is regulated at the transcriptional level by various transcription factors, including SIRT1, MZF1, and Nrf2. mTORC2's activity is also regulated by microRNAs, which can modulate its expression in different tissues. mTORC2 localizes to various membrane compartments, including the plasma membrane, endoplasmic reticulum, mitochondria-associated ER membranes, lysosomes, endosomes, and the nucleus. Its localization to these compartments allows it to phosphorylate its substrates. mTORC2 is activated by growth factors, hormones, nutrients, and stress conditions. It is also regulated by G-protein coupled receptor signaling. mTORC2 is activated by insulin, growth factors, and PI3K. The binding of insulin to the insulin receptor promotes the autophosphorylation of the receptor, leading to the recruitment of signaling molecules that bind to its phosphorylated residues. PI3K generates PIP3 by phosphorylating PtdIns(4,5)P2, which activates mTORC2. The intensity of receptor stimulation modulates mTORC2 signaling. mTORC2The mTORC2 signaling network: targets and cross-talks The mechanistic target of rapamycin (mTOR) controls cell metabolism in response to growth signals and stress. mTOR functions through two complexes, mTORC1 and mTORC2. While mTORC1 is inhibited by rapamycin, mTORC2 is not. mTORC2 is activated by anabolic signals and stress and mediates signals from growth factor and G-protein coupled receptors. It regulates Akt, PKC, and SGK, which are members of the AGC kinase family. mTORC2 is regulated by cellular stimuli, including compartmentalization and modulation of its components. Phosphorylation of its substrates, particularly AGC kinases, mediates its functions in growth, proliferation, survival, and differentiation. mTORC2 also interacts with other signaling and metabolic components, and its activity is crucial for metabolic reprogramming and cell survival. The review discusses the regulation and targets of mTORC2, how it intersects with other pathways, and how to target mTORC2 for disease treatment. mTORC2 is composed of mTOR, rictor, and SIN1. It is a dimer of multi-subunit complexes and has a rhombus-like shape. mTOR is a PI3K-related kinase with specific domains that modulate its function. mTORC2 is regulated by post-translational modifications, including phosphorylation, acetylation, ubiquitination, and malonylation. These modifications affect mTORC2's expression, localization, and activity. mTORC2 also interacts with other proteins such as DEPTOR, Sestrin2, and Protor, which modulate its activity. The expression of mTORC2 components is regulated at the transcriptional level by various transcription factors, including SIRT1, MZF1, and Nrf2. mTORC2's activity is also regulated by microRNAs, which can modulate its expression in different tissues. mTORC2 localizes to various membrane compartments, including the plasma membrane, endoplasmic reticulum, mitochondria-associated ER membranes, lysosomes, endosomes, and the nucleus. Its localization to these compartments allows it to phosphorylate its substrates. mTORC2 is activated by growth factors, hormones, nutrients, and stress conditions. It is also regulated by G-protein coupled receptor signaling. mTORC2 is activated by insulin, growth factors, and PI3K. The binding of insulin to the insulin receptor promotes the autophosphorylation of the receptor, leading to the recruitment of signaling molecules that bind to its phosphorylated residues. PI3K generates PIP3 by phosphorylating PtdIns(4,5)P2, which activates mTORC2. The intensity of receptor stimulation modulates mTORC2 signaling. mTORC2