Glucose withdrawal activates a positive feedback loop resulting in supra‐physiological phospho‐tyrosine signaling and ROS‐mediated cell death. Glucose.

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Glucose withdrawal activates a positive feedback loop resulting in supra‐physiological phospho‐tyrosine signaling and ROS‐mediated cell death. Glucose withdrawal activates a positive feedback loop resulting in supra‐physiological phospho‐tyrosine signaling and ROS‐mediated cell death. In cells dependent on glucose for survival, glucose and pyruvate deprivation induces oxidative stress driven by NOX and mitochondria. This oxidative stress provokes a positive feedback loop in which NOX and mitochondria generate superoxide anion (O2−), which dismutes to hydrogen peroxide (H2O2) and inhibits PTPs by oxidation (e.g., PTP‐1B and PTEN). Without the negative regulation of PTPs, TKs including EGFR and Src activate NOX at focal adhesions, further amplifying ROS generation. This glucose withdrawal‐induced positive feedback loop results in supra‐physiological levels of tyrosine phosphorylation and ROS‐mediated cell death. Nicholas A Graham et al. Mol Syst Biol 2012;8:589 © as stated in the article, figure or figure legend