14-3-3 and Erlin proteins differentially interact with RIPK2 complexes.

The receptor interacting serine/threonine kinase 2 (RIPK2) is essential for signal transduction induced by the pattern-recognition receptors NOD1 and NOD2. Upon NOD1/2 activation RIPK2 forms complexes in the cytoplasm of human cells. Here, we identified the molecular composition of these complexes. Infection with Shigella flexneri to activate NOD1-RIPK2 revealed that RIPK2 formed dynamic interactions with several cellular proteins, including A20, Erlin-1, Erlin-2 and 14-3-3. Whereas interaction of RIPK2 with 14-3-3 proteins was strongly reduced upon infection with Shigella, Erlin-1 and Erlin-2 specifically bound to RIPK2 complexes. The interaction of these proteins with RIPK2 was validated by protein binding assays and immunofluorescence staining. Beside bacterial activation of NOD1/2, depletion of the E3 ligase XIAP and treatment with RIPK2 inhibitors also leads to the formation of RIPK2 cytosolic complexes. Whereas Erlin-1 and Erlin-2 were recruited to RIPK2 complexes following XIAP inhibition, they did not associate with RIPK2 structures induced by RIPK2 inhibitors. While the specific recruitment of Erlin-1/2 to RIPK2 suggests a role for these proteins in innate immune signaling, the biological response regulated by the Erlin-1/2-RIPK2 association remains to be determined. © 2021. Published by The Company of Biologists Ltd.

Citation

Heidrun Steinle, Kornelia Ellwanger, Nora Mirza, Selina Brise, Ioannis Kienes, Jens Pfannstiel, Thomas A Kufer. 14-3-3 and Erlin proteins differentially interact with RIPK2 complexes. Journal of cell science. 2021 Jun 04

PMID: 34086049

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