Cellular regulation by hydrogen peroxide.
Substantial evidence suggests that the transient production of H(2)O(2) is an important signaling event triggered by the activation of various cell surface receptors. Understanding the intracellular messenger function of H(2)O(2) calls for studies of how receptor occupation elicits the production of H(2)O(2), what kinds of molecules are targeted by the produced H(2)O(2), and how H(2)O(2) is eliminated after the completion of its mission. Recent studies suggest that growth factor-induced H(2)O(2) production requires the activation of PtdIns 3-kinase. The essential role of PtdIns 3-kinase is likely to provide PI(3,4,5)P(3) that recruits and activates a guanine nucleotide exchange factor of Rac, which is required for the activation of NADPH oxidase. The targets of H(2)O(2) action include proteins that contain a reactive Cys residue. Thus, H(2)O(2) produced in response to growth factor causes inactivation of protein tyrosine phosphatases in various cells by oxidizing specifically the catalytic Cys. These results, together with other observations, indicate that the activation of a receptor tyrosine kinase per se by binding of the corresponding growth factor might not be sufficient to increase the steady-state level of protein tyrosine phosphorylation in cells. Rather, the concurrent inhibition of protein tyrosine phosphatases by H(2)O(2) might also be required. Peroxiredoxins, members of a newly discovered family of peroxidases, efficiently reduced the intracellular level of H(2)O(2) produced in the cells stimulated with various cell surface ligands. Furthermore, the activity of peroxiredoxin enzymes seems to be regulated via protein phosphorylation as in the case of many other intracellular messenger metabolizing enzymes.
Rhee
Sue Goo
SG
Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. sgrhee@nih.gov
Chang
Tong-Shin
TS
Bae
Yun Soo
YS
Lee
Seung-Rock
SR
Kang
Sang Won
SW
D000818:Animals; D002468:Cell Physiological Phenomena; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D010544:Peroxidases / Q000502:physiology; D054464:Peroxiredoxins; D011506:Proteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology
D011506:Proteins; D011956:Receptors, Cell Surface; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins