Figure 9.

Altered mTORC1 and mTORC2 signaling in AS mice. Schematic representation showing the essential elements in mTORC1 and mTORC2 signaling pathways and their alterations in AS mice. TSC2 is a negative regulator of mTORC1 and is generally degraded in an Ube3A-dependent manner. Ube3A deficiency results in increased TSC2 levels and its inhibitory phosphorylation, which produces an overactivation of mTORC1. mTORC1–S6K1 overactivation suppresses mTORC2 by phosphorylating rictor and potentially (dash line) inhibits TSC1/2 activity by phosphorylating TSC2. Red line, Increased activity in AS mice; gray line, decreased activity in AS mice. PIP2, Phosphatidylinositol-4,5-biphosphate; PIP3, phosphatidylinositol-3,4,5-triphosphate; PTEN, phosphatase and tensin homolog; PDK1, pyruvate dehydrogenase lipoamide kinase isozyme 1; 4EBP1, 4E-binding protein 1.