Figure 10.

Model for Foxo3 regulation of hematopoietic progenitor cell activity. In hematopoietic progenitors, cytokine receptor signalling generates ROS that further activate receptor signalling (AKT/mTOR), leading to cell proliferation, increased production of ROS and ultimate induction of Foxo3 nuclear localization once ROS are accumulated above certain threshold. Signalling is modulated by cytokine receptor regulators including Lnk, a negative regulator. In Foxo3^−/− hematopoietic progenitors, decreased expression of Lnk, associated with significant increase in ROS accumulation, enhance cytokine-mediated signalling, leading to myeloproliferation.