Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins.
Hydrogen peroxide (H2O2) accumulates transiently in various cell types stimulated with peptide growth factors and participates in receptor signaling by oxidizing the essential cysteine residues of protein tyrosine phosphatases and the lipid phosphatase PTEN. The reversible inactivation of these phosphatases by H2O2 is likely required to prevent futile cycles of phosphorylation-dephosphorylation of proteins and phosphoinositides. The accumulation of H2O2 is possible even in the presence of large amounts of the antioxidant enzymes peroxiredoxin I and II in the cytosol, probably because of a built-in mechanism of peroxiredoxin inactivation that is mediated by H2O2 and reversed by an ATP-dependent reduction reaction catalyzed by sulfiredoxin.
Rhee
Sue Goo
SG
Laboratory of Cell Signaling, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. sgrhee@nih.gov
Kang
Sang Won
SW
Jeong
Woojin
W
Chang
Tong-Shin
TS
Yang
Kap-Seok
KS
Woo
Hyun Ae
HA
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D051059:PTEN Phosphohydrolase; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D025521:Tumor Suppressor Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human