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A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.

ABSTRACT: 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.

SUBMITTER: Heim VJ 

PROVIDER: S-EPMC7645253 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.

Heim Valentin J VJ   Dagley Laura F LF   Stafford Che A CA   Hansen Fynn M FM   Clayer Elise E   Bankovacki Aleksandra A   Webb Andrew I AI   Lucet Isabelle S IS   Silke John J   Nachbur Ueli U  

EMBO reports 20200921 11

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 l  ...[more]

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