T cell receptor-mediated signaling induces GRP78 expression in T cells: the implications in maintaining T cell viability |
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Authors: | Takano Shinichi Ando Takashi Hiramatsu Nobuhiko Kanayama Asuka Maekawa Shinya Ohnuma Yuko Enomoto Nobuyuki Ogawa Hideoki Paton Adrienne W Paton James C Kitamura Masanori Nakao Atsuhito |
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Institution: | a Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan b Department of Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan c Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan d Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan e School of Molecular and Biomedical Science, University of Adelaide, SA 5005, Australia |
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Abstract: | The 78-kDa glucose-regulated protein (GRP78) is an important molecular chaperone in the endoplasmic reticulum (ER) induced by various stresses. This study showed that stimulation with anti-CD3 mAb, PMA plus ionomycin, or an antigen increased the levels of GRP78 mRNA in primary T cells, which was inhibited by Ca2+ chelators EGTA and BAPTA-AM and by an inhibitor of calcineurin FK506. In addition, the specific knockdown of GRP78 protein expression induced apoptosis in mouse EL-4 T cell line associated with CHOP induction and caspase-3 activation. Furthermore, overexpression of GRP78 inhibited PMA/ionomycin-induced cell death in EL-4 cells. Collectively, GRP78 expression is induced by TCR activation via a Ca2+-dependent pathway and may play a critical role in maintaining T cell viability in the steady and TCR-activated states. These results suggest a novel regulatory mechanism and an essential function of GRP78 in T cells. |
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Keywords: | GRP78 the 78-kDa glucose-regulated protein ER endoplasmic reticulum TCR T cell receptor AICD activation induced cell death mAb monoclonal antibody |
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