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

Figure 2

The signaling network of mTORC2. (a) Schematic representation of AGC kinases downstream of mTORC2. The major positions for phosphorylation are indicated. (b) As ligands, growth factors bind to the membrane receptor, receptor tyrosine kinase (RTK), which activates PI3K to phosphorylate PIP2 to PIP3 at the plasma membrane. PTEN (phosphatase and tensin homolog) dephosphorylates PIP3 and is a key negative regulator of PI3K signaling. PIP3 or other unknown factors activate mTORC2 in distinct manners to promote the phosphorylation of conserved motifs in several AGC kinases (Akt, PKC, and SGK1). For maximal activation, Akt is phosphorylated at T308 and S473 by PDK1 and mTORC2, respectively, and subsequently promotes the activation of mTORC1, which is characterized by phosphorylation of several downstream effectors, including S6K, 4E-BP1, and ULK1. There are several other upstream regulators which can also regulate mTORC2 activity, including amino acids, ROS, ribosome, TSC complex, and GTPases, through distinct mechanisms. Description of the abbreviations listed is contained within this review.

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