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• W2026123712 endingPage "359" @default.
• W2026123712 startingPage "347" @default.
• W2026123712 abstract "Activation of T lymphocytes requires protein kinase C theta (PKC-θ) and an appropriately elevated free intracellular Ca2+ concentration ([Ca2+]i). Here, we show that phorbol 12 myristate 13-acetate (PMA) inhibited Ca2+ influx in wild-type but not PKC-θ−/− T cells, suggesting that PKC-θ plays a role in PMA-mediated inhibition of Ca2+ influx. In contrast, T cell receptor (TCR) crosslinking in the same PKC-θ−/− T cells did result in significantly decreased [Ca2+]i compared to wild-type T cells, suggesting a positive role for PKC-θ in TCR-mediated Ca2+ mobilization. In PKC-θ−/− mice, peripheral mature T cells, but not developing thymocytes, displayed significantly decreased TCR-induced Ca2+ influx and nuclear factor of activated T cells (NFAT) translocation upon sub-optimal TCR crosslinking. The decreased intracellular free Ca2+ was due to changes in Ca2+ influx but not efflux, as observed in extracellular and intracellular Ca2+ mobilization studies. However, these differences in Ca2+ influx and nuclear factor of activated T cells (NFAT) translocation disappeared with increasing intensity of TCR crosslinking. The enhancing effect of PKC-θ on Ca2+ influx is not only dependent on the strength of TCR crosslinking but also on the developmental stage of T cells. The underlying mechanism involved phospholipase Cγ1 activation and inositol triphosphate production. Furthermore, knockdown of endogenous PKC-θ expression in Jurkat cells resulted in significant inhibition of TCR-induced activation of NFAT, as evidenced from NFAT reporter studies. Forced expression of a constitutively active form of calcineurin in PKC-θ−/− Jurkat cells could readily overcome the above inhibition. Thus, PKC-θ can both positively and negatively regulate the Ca2+ influx that is critical for NFAT activity." @default.
• W2026123712 created "2016-06-24" @default.
• W2026123712 creator A5004672379 @default.
• W2026123712 creator A5042509710 @default.
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• W2026123712 date "2006-01-01" @default.
• W2026123712 modified "2023-09-26" @default.
• W2026123712 title "Differential Roles of PKC-θ in the Regulation of Intracellular Calcium Concentration in Primary T Cells" @default.
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• W2026123712 doi "https://doi.org/10.1016/j.jmb.2005.10.043" @default.
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