Scheme 4.
The cross-talk between FPR2 and EGFR is mediated by NADPH oxidase-dependent superoxide generation and by c-Src activation. Stimulation of CaLu-6 cells with WKYMVm induces p47phox phosphorylation and translocation, NADPH oxidase activation, c-Src kinase activity and EGFR transactivation. Oxidation of the cysteine sulfhydryl group of phosphotyrosine phosphatase (PTPase) by reactive oxygen species tightly controls the activity of EGFR, shifting the equilibrium state of EGFR from non-phosphorylated to phosphorylated. c-Src is also sensitive to intracellular redox conditions and plays a key role in bridging signals from FPR2 to EGFR in these cells. NADPH oxidase-dependent superoxide generation can inactivate PTPases that control the c-Src phosphorylation status.