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- W4385686906 abstract "Developing CD4+CD8+ double-positive (DP) thymocytes with randomly generated T cell receptors (TCRs) undergo positive (maturation) or negative (apoptosis) selection on the basis of the strength of TCR stimulation. Selection fate is determined by engagement of TCR ligands with a subtle difference in affinity, but the molecular details of TCR signaling leading to the different selection outcomes have remained unclear. We performed phosphoproteome analysis of DP thymocytes and found that p90 ribosomal protein kinase (RSK) phosphorylation at Thr562 was induced specifically by high-affinity peptide ligands. Such phosphorylation of RSK triggered its translocation to the nucleus, where it phosphorylated the nuclear receptor Nur77 and thereby promoted its mitochondrial translocation for apoptosis induction. Inhibition of RSK activity protected DP thymocytes from antigen-induced cell death. We propose that RSK phosphorylation constitutes a mechanism by which DP thymocytes generate a stepwise and binary signal in response to exposure to TCR ligands with a graded affinity." @default.
- W4385686906 created "2023-08-10" @default.
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- W4385686906 date "2023-09-01" @default.
- W4385686906 modified "2023-10-17" @default.
- W4385686906 title "A stepwise and digital pattern of RSK phosphorylation determines the outcome of thymic selection" @default.
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- W4385686906 doi "https://doi.org/10.1016/j.isci.2023.107552" @default.
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