Department of Physiology and Centro Singular de Medicina Molecular y Enfermedades Crónicas (CIMUS), University of Santiago de Compostela, Spain.
J Biol Chem. 2012 Mar 30;287(14):11556-65. doi: 10.1074/jbc.M111.320259. Epub 2012 Jan 30.
While studying the functions of CCM3/PDCD10, a gene encoding an adaptor protein whose mutation results in vascular malformations, we have found that it is involved in a novel response to oxidative stress that results in phosphorylation and activation of the ezrin/radixin/moesin (ERM) family of proteins. This phosphorylation protects cells from accidental cell death induced by oxidative stress. We also present evidence that ERM phosphorylation is performed by the GCKIII kinase Mst4, which is activated and relocated to the cell periphery after oxidative stress. The cellular levels of Mst4 and its activation after oxidative stress depend on the presence of CCM3, as absence of the latter impairs the phosphorylation of ERM proteins and enhances death of cells exposed to reactive oxygen species. These findings shed new light on the response of cells to oxidative stress and identify an important pathophysiological situation in which ERM proteins and their phosphorylation play a significant role.
在研究 CCM3/PDCD10 基因（一种编码衔接蛋白的基因，其突变导致血管畸形）的功能时，我们发现它参与了一种新的应对氧化应激的反应，导致 ezrin/radixin/moesin（ERM）蛋白家族的磷酸化和激活。这种磷酸化可保护细胞免受氧化应激引起的意外细胞死亡。我们还提供了证据表明，ERM 磷酸化是由 GCKIII 激酶 Mst4 完成的，该激酶在氧化应激后被激活并转移到细胞外周。氧化应激后细胞内 Mst4 的水平及其激活取决于 CCM3 的存在，因为后者的缺失会损害 ERM 蛋白的磷酸化并增强暴露于活性氧的细胞的死亡。这些发现为细胞对氧化应激的反应提供了新的视角，并确定了一种重要的病理生理情况，其中 ERM 蛋白及其磷酸化起着重要作用。
