RIPK2 上的一个调控区域对于 XIAP 的结合和 NOD 信号活性是必需的。
A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.
机构信息
The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia.
Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
出版信息
EMBO Rep. 2020 Nov 5;21(11):e50400. doi: 10.15252/embr.202050400. Epub 2020 Sep 21.
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.
通过细胞内病原体受体核苷酸结合寡聚化结构域蛋白 NOD1 和 NOD2 进行信号转导需要受体相互作用激酶 2（RIPK2），它是一种衔接激酶，可以作为治疗各种炎症性疾病的靶点。然而，RIPK2 如何促进 NOD 信号转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 标签的 RIPK2 敲入小鼠，以在体内水平研究 NOD 信号转导机制。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。与其他报道一样，我们在 NOD2 信号转导过程中没有检测到 RIPK2 赖氨酸 209 的泛素化。然而，通过定点突变，我们确定了 RIPK2 上的一个新的调节区域，该区域决定了与 E3 连接酶 XIAP 的关键相互作用以及下游信号转导结果。
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