Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes.
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 Bim activation. G5PR is essential for the survival of DP cells during thymocyte development.
Xing
Yan
Y
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Wang
Xiaodan
X
Igarashi
Hideya
H
Kawamoto
Hiroshi
H
Sakaguchi
Nobuo
N
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000201:enzymology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology*
D053222:Fas Ligand Protein; D021122:Protein Subunits; D048031:JNK Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D053148:Caspase 3