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• W1906673334 endingPage "7406" @default.
• W1906673334 startingPage "7398" @default.
• W1906673334 abstract "The Src family kinase Lck is essential for T cell Ag receptor-mediated signaling. In this study, we report the effects of acute elimination of Lck in Jurkat TAg and primary T cells using RNA interference mediated by short-interfering RNAs. In cells with Lck knockdown (kd), proximal TCR signaling was strongly suppressed as indicated by reduced zeta-chain phosphorylation and intracellular calcium mobilization. However, we observed sustained and elevated phosphorylation of ERK1/2 in Lck kd cells 30 min to 2 h after stimulation. Downstream effects on immune function as determined by activation of a NFAT-AP-1 reporter, and TCR/CD28-stimulated IL-2 secretion were strongly augmented in Jurkat and primary T cells, respectively. As expected, overexpression of SHP-1 in Jurkat cells inhibited TCR-induced NFAT-AP-1 activation, but this effect could be overcome by simultaneous kd of Lck. Furthermore, acute elimination of Lck also suppressed TCR-mediated activation of SHP-1, suggesting the possible role of SHP-1 in a negative feedback loop originating from Lck. This report underscores Lck as an important mediator of proximal TCR signaling, but also indicates a suppressive role on downstream immune function." @default.
• W1906673334 created "2016-06-24" @default.
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• W1906673334 date "2005-12-01" @default.
• W1906673334 modified "2023-10-02" @default.
• W1906673334 title "Short-Interfering RNA-Mediated Lck Knockdown Results in Augmented Downstream T Cell Responses" @default.
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• W1906673334 doi "https://doi.org/10.4049/jimmunol.175.11.7398" @default.
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• W1906673334 hasPublicationYear "2005" @default.
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