Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning

Sheng-Li Cai; Andrew R. Tee; John D. Short; Judith M. Bergeron; Jinhee Kim; Jianjun Shen; Ruifeng Guo; Charles L. Johnson; Kaoru Kiguchi; Cheryl Lyn Walker

doi:10.1083/jcb.200507119

Figure 10.

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Model for regulation of tuberin under conditions of mitogenic sufficiency. (A) Tuberin normally functions as a GAP for Rheb within an intracellular membrane compartment, inhibiting Rheb and mTOR signaling, which suppresses cell growth. (B) Upon stimulation by growth factors, AKT is activated, leading to phosphorylation and cytosolic sequestration of tuberin by 14-3-3 proteins. This cytosolic translocation relieves tuberin repression of the Rheb-mTOR signaling, stimulating cell growth.