Ewha Womans University, Seoul, Korea.
Cell. 2010 Feb 19;140(4):517-28. doi: 10.1016/j.cell.2010.01.009.
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.
尽管 H(2)O(2) 具有毒性，但它作为一种信号分子被产生，以响应细胞表面受体的激活，氧化效应物（如蛋白酪氨酸磷酸酶）中的关键半胱氨酸残基。然而，在丰富的解毒酶过氧化物酶（Prx）I 和 II 存在的情况下，如何达到超过修饰效应物所需的 H(2)O(2) 浓度，这一点仍不清楚。我们现在表明，与膜结合的 PrxI 会在酪氨酸-194 上发生瞬时磷酸化，从而在体外通过生长因子或免疫受体刺激的细胞中和在小鼠愈合性皮肤创伤边缘的细胞中失活。PrxI 的局部失活允许 H(2)O(2) 在膜周围短暂积累，信号成分在此处浓缩，同时防止 H(2)O(2) 在其他地方积累。相比之下，PrxII 的失活不是通过磷酸化，而是通过其催化半胱氨酸在持续氧化应激期间的过度氧化。
