A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity
- Heim, VJ; Dagley, LF; Stafford, CA; Hansen, FM; Clayer, E; Bankovacki, A; Webb, AI; Lucet, IS; Silke, J; Nachbur, U;
- Journal Title
- EMBO Reports
- 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.
- WEHI Research Division(s)
- Inflammation; Advanced Technology And Biology; Chemical Biology; Ubiquitin Signalling
- PubMed ID
- Publisher's Version
- ARC Grants
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- Refer to copyright notice on published article.
Creation Date: 2020-10-02 10:28:04Last Modified: 2021-03-18 11:46:38