Signaling via the intracellular pathogen receptors nucleotide‐binding oligomerization domain‐containing proteins NOD1 and NOD2 requires receptor interacting kinase 2 (RIPK2), an adaptor kinase that can be targeted for the treatment of various inflammatory diseases. However, the molecular mechanisms of how RIPK2 contributes to NOD signaling are not completely understood. We generated FLAG‐tagged RIPK2 knock‐in mice using CRISPR/Cas9 technology to study NOD signaling mechanisms at the endogenous level. Using cells from these mice, we were able to generate a detailed map of post‐translational modifications on RIPK2. Similar to other reports, we did not detect ubiquitination of RIPK2 lysine 209 during NOD2 signaling. However, using site‐directed mutagenesis we identified a new regulatory region on RIPK2, which dictates the crucial interaction with the E3 ligase XIAP and downstream signaling outcomes.

中文翻译：

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XIAP 结合和 NOD 信号活性需要 RIPK2 上的调节区。

通过细胞内病原体受体核苷酸结合寡聚结构域的蛋白质 NOD1 和 NOD2 发出信号需要受体相互作用激酶 2 (RIPK2)，这是一种可靶向治疗各种炎症性疾病的衔接激酶。然而，RIPK2 如何参与 NOD 信号传导的分子机制尚不完全清楚。我们使用 CRISPR/Cas9 技术生成了带有 FLAG 标记的 RIPK2 敲入小鼠，以研究内源性水平的 NOD 信号传导机制。使用这些小鼠的细胞，我们能够生成 RIPK2 翻译后修饰的详细图谱。与其他报告类似，我们没有在 NOD2 信号传导过程中检测到 RIPK2 赖氨酸 209 的泛素化。然而，使用定点诱变，我们在 RIPK2 上发现了一个新的调控区域，