Sharif Ariane, Canton Brigitte, Junier Marie-Pierre, Chneiweiss Hervé
INSERM U114, Department de Neuropharmacologie, Collège de France, 75231 Paris Cedex 05, France.
Ann N Y Acad Sci. 2003 Dec;1010:43-50. doi: 10.1196/annals.1299.006.
PEA-15 is a small protein (15 kDa) that was first identified as an abundant phosphoprotein in brain astrocytes and subsequently shown to be widely expressed in different tissues and highly conserved among mammals. It is composed of an N-terminal death effector domain (DED) and a C-terminal tail of irregular structure. PEA-15 is regulated by multiple calcium-dependent phosphorylation pathways. PEA-15 is ideally positioned to play a major role in signal integration. Accordingly, it has been demonstrated that PEA-15 diverts astrocytes from TNFalpha-triggered apoptosis and regulates the actions of the ERK MAP kinase cascade by binding to ERK and altering its subcellular localization. Expression of PEA-15 directs TNFalpha outcomes toward survival, whereas its absence allows the development of the cytokine-induced cell death.
PEA - 15是一种小蛋白（15千道尔顿），最初被鉴定为脑星形胶质细胞中一种丰富的磷蛋白，随后发现它在不同组织中广泛表达，且在哺乳动物中高度保守。它由一个N端死亡效应结构域（DED）和一个结构不规则的C端尾部组成。PEA - 15受多种钙依赖性磷酸化途径调控。PEA - 15在信号整合中具有发挥主要作用的理想定位。因此，已证明PEA - 15通过与ERK结合并改变其亚细胞定位，使星形胶质细胞从肿瘤坏死因子α（TNFα）触发的凋亡中转向，并调节ERK丝裂原活化蛋白激酶级联反应的作用。PEA - 15的表达使TNFα的作用导向细胞存活，而其缺失则会导致细胞因子诱导的细胞死亡。
