Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes

Yan Xing; Xiaodan Wang; Hideya Igarashi; Hiroshi Kawamoto; Nobuo Sakaguchi

doi:10.1016/j.molimm.2007.10.028

Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes

Yan Xing, Xiaodan Wang, Hideya Igarashi, Hiroshi Kawamoto, Nobuo Sakaguchi

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Pages (from-to)	2028-2037
Number of pages	10
Journal	Molecular Immunology
Volume	45
Issue number	7
DOIs	https://doi.org/10.1016/j.molimm.2007.10.028
State	Published - Apr 2008

Bibliographical note

Funding Information:
This work was supported by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency. This work was also supported, in part, by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases launched as a project commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by Japan–China Cooperative Life Science Program and JSPS Asia and Africa Science Platform Program, and by JSPS KAKENHI (17590440). Y.X. was supported by a Postdoctoral Fellowship from the Japan Society for the Promotion of Science (JSPS). X.W. was supported by Japanese Government (Monbusho) Scholarship.

Keywords

Apoptosis
Bim
JNK
T cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes",

abstract = "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.",

keywords = "Apoptosis, Bim, JNK, T cells",

author = "Yan Xing and Xiaodan Wang and Hideya Igarashi and Hiroshi Kawamoto and Nobuo Sakaguchi",

note = "Funding Information: This work was supported by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency. This work was also supported, in part, by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases launched as a project commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by Japan–China Cooperative Life Science Program and JSPS Asia and Africa Science Platform Program, and by JSPS KAKENHI (17590440). Y.X. was supported by a Postdoctoral Fellowship from the Japan Society for the Promotion of Science (JSPS). X.W. was supported by Japanese Government (Monbusho) Scholarship.",

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AU - Kawamoto, Hiroshi

AU - Sakaguchi, Nobuo

N1 - Funding Information: This work was supported by Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency. This work was also supported, in part, by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases launched as a project commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by Japan–China Cooperative Life Science Program and JSPS Asia and Africa Science Platform Program, and by JSPS KAKENHI (17590440). Y.X. was supported by a Postdoctoral Fellowship from the Japan Society for the Promotion of Science (JSPS). X.W. was supported by Japanese Government (Monbusho) Scholarship.

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N2 - 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.

AB - 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.

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Protein phosphatase subunit G5PR that regulates the JNK-mediated apoptosis signal is essential for the survival of CD4 and CD8 double-positive thymocytes

Abstract

Bibliographical note

Keywords

UN SDGs

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