Figure 5. Model of compartmentalized NOX-ROS downstream signaling. Constellation of intracellular mechanisms channeling NOX-derived H₂O₂ to kinase targets and various phenotype shifts.

Diagrammatic representation of how oxidative and phosphorylative mechanisms in the vicinity of the NOX2 source in lipid rafts can theoretically channel NOX-derived H₂O₂ for redox signaling. In this scenario, growth factor receptor (GFR) transactivates and stimulates NOX2 assembly and H₂O₂ production which, in turn, activates a target kinase. GFR’s phosphorylation and inhibition of peroxiredoxin I (Prx I) prevent its degradation of NOX2-derived H₂O₂. Simultaneously, NOX2 H₂O₂ oxidatively inactivates Prx II further augmenting steady-state H₂O₂ in the vicinity of NOX2 and its target kinase. Additionally, H₂O₂ via cysteine oxidation of phosphatases inhibits phosphatase activity which is permissive of target kinase activity and feedforward signaling. Away from NOX2, Prx I and II remain active and scavenge H₂O₂ from other potentially interfering sources. Collectively, these effects protect and allow localized H₂O₂ to rise close to target kinase(s) and propagate downstream signaling leading to an array of phenotypic shifts. In sum, these reactions restrict and direct NOX- H₂O₂ while, in other areas of the cell, active Prxs degrade H₂O₂ preventing interference with signaling (see section 2.4).