Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes
Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes
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DOI：
10.1016/j.molimm.2007.10.028
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Sakaguchi, Nobuo
中科院分区：
文献类型：
--
作者：
Xing, Yan;Wang, Xiaodan;Sakaguchi, Nobuo
早期T系细胞是通过对胸腺上皮细胞和树突状细胞表面MHC分子呈递的肽组分的特异性识别而在胸腺中被选择的。蛋白磷酸酶2a组分G5PR作为凋亡和存活信号的潜在调节剂，调节b细胞中Bim的磷酸化。在胸腺细胞的选择过程中，我们研究了G5PR是否参与了类似凋亡通路对细胞存活的调控。t细胞特异性G5PR敲除（G5PR(-/-)）小鼠表现出胸腺萎缩，胸腺细胞数量显著减少，特别是CD4和CD8双阳性（DP）胸腺细胞数量减少10倍，成熟的单阳性（SP）细胞数量很少。G5pr（-/-）胸腺细胞在双阴性（DN）期向DP期过渡时增殖分化能力正常，但在DP期凋亡易感性明显增加。G5PR缺失不影响胸腺细胞中Bim的激活，但导致JNK和Caspase-3的超激活，Fas配体（FasL）表达增强，表明G5PR调节胸腺细胞独特的凋亡信号，参与JNK介导的Caspase-3激活，而不参与Bint激活。在胸腺细胞发育过程中，G5PR对DP细胞的存活至关重要。(C) 2007 Elsevier Ltd.版权所有。
Early T lineage cells are selected in the thymus by the specific recognition of peptide components presented by MHC molecules on the surface of thymic epithelial cells and dendritic cells. As a potential regulator of the apoptotic and survival signals, the protein phosphatase 2A-component G5PR regulates Bim phosphorylation in B-cells. Here, we studied whether G5PR is involved in the regulation of the similar apoptotic pathway for cell survival during the selection of thymocytes. T-cell-specific G5PR knockout (G5pr(-/-)) mice displayed thymic atrophy, significant reduction in thymocyte numbers, particularly a 10-fold decrease in the number of CD4 and CD8 double-positive (DP) thymocytes and few mature single-positive (SP) cells. G5pr(-/-) thymocytes exhibited normal potential of proliferation and differentiation during the transition from double-negative (DN) to DP stage, but significantly increased susceptibility to apoptosis at the DP stage. G5PR deficiency did not affect on Bim activation in thymocytes, but caused hyper-activation of JNK and Caspase-3 with augmented Fas ligand (FasL) expression, indicating that G5PR regulates the thymocyte unique apoptotic signal involved in JNK-mediated Caspase-3 activation but not in Bint activation. G5PR is essential for the survival of DP cells during thymocyte development. (C) 2007 Elsevier Ltd. All rights reserved.