Hydrogen peroxide as intracellular messenger production, target, and elimination

Engagement of peptide growth-factor receptors induces a transient production of low levels of H2O2 in various cells. The H₂O ₂ response to platelet-derived growth factor requires the intrinsic tyrosine kinase activity of the receptor as well as the activation of phosphatidylinositol 3-kinase (PI 3-kinase). It appears that PtdIns(3,4,5)P3, a product of PI 3-kinase, is necessary to activate an isoform of NADPH oxidase through the small GTP-binding protein Rac. H₂O₂ thus produced propagates its signal by specifically acting on protein tyrosine phosphatases. And enhancement of protein tyrosine phosphorylation in growth factor-stimulated cells depends on the H₂O₂ production. This is probably because the activation of a receptor tyrosine kinase is not sufficient to increase the steady-state level of protein tyrosine phosphorylation in cells, and that concurrent inhibition of protein tyrosine phosphatase by H2O2 might be needed as well. Elimination of H₂O ₂ appears to be an extensively regulated process. Peroxiredoxin I (Prx I) and Prx II, two cytosolic thioredoxin-dependent peroxidases, are inactivated at the G2-M transition through Cdc2 kinase-dependent phosphorylation.