Bimodal regulation of Sestrin2
A) Sestrin2 is a leucine sensor and inhibitor of mTORC1 signaling in response to stresses. Sestrin2, leucine, and GATOR2 exist in a equilibrium in the cell that dictates mTORC1 activity in response to both leucine levels and other stresses. Increasing leucine levels pushes the Sestrin2-leucine equilibrium forward such that more GATOR2 is free, leading to increased mTORC1 signaling. Increasing levels of Sestrin2, downstream of ATF4 in response to cellular stresses, pushes the Sestrin2-GATOR2 equilibrium forward, inhibiting mTORC1 signaling.
B) Schematic depicting mTORC1 activity in response to increasing Sestrin2 levels, at constant levels of GATOR2 and leucine.
C) Diagram showing how modulating leucine levels will impact mTORC1 activity at varying cellular levels of Sestrin2.