title: Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling.
abstract: Despite its toxicity, H(2)O(2) is produced as a signaling molecule that oxidizes critical cysteine residues of effectors such as protein tyrosine phosphatases in response to activation of cell surface receptors. It has remained unclear, however, how H(2)O(2) concentrations above the threshold required to modify effectors are achieved in the presence of the abundant detoxification enzymes peroxiredoxin (Prx) I and II. We now show that PrxI associated with membranes is transiently phosphorylated on tyrosine-194 and thereby inactivated both in cells stimulated via growth factor or immune receptors in vitro and in those at the margin of healing cutaneous wounds in mice. The localized inactivation of PrxI allows for the transient accumulation of H(2)O(2) around membranes, where signaling components are concentrated, while preventing the toxic accumulation of H(2)O(2) elsewhere. In contrast, PrxII was inactivated not by phosphorylation but rather by hyperoxidation of its catalytic cysteine during sustained oxidative stress.
authors.affiliation: Ewha Womans University, Seoul, Korea. hawoo@ewha.ac.kr
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Yim
authors.forename: Dong Hae
authors.initials: DH
authors.lastname: Shin
authors.forename: Dongmin
authors.initials: D
authors.lastname: Kang
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D041681:NIH 3T3 Cells; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014945:Wound Healing
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D014443:Tyrosine; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D020794:Receptor Protein-Tyrosine Kinases