Laurien, Lucie, Nagata, Masahiro, Schuenke, Hannah, Delanghe, Tom, Wiederstein, Janica L., Kumari, Snehlata, Schwarzer, Robin, Corona, Teresa, Krueger, Marcus, Bertrand, Mathieu J. M., Kondylis, Vangelis and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2020). Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 and other receptors, and has been implicated in the pathogenesis of inflammatory and degenerative diseases. RIPK1 kinase activity induces apoptosis and necroptosis, however the mechanisms and phosphorylation events regulating RIPK1-dependent cell death signaling remain poorly understood. Here we show that RIPK1 autophosphorylation at serine 166 plays a critical role for the activation of RIPK1 kinase-dependent apoptosis and necroptosis. Moreover, we show that S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis of inflammatory pathologies in vivo in four relevant mouse models. Mechanistically, we provide evidence that trans autophosphorylation at S166 modulates RIPK1 kinase activation but is not by itself sufficient to induce cell death. These results show that S166 autophosphorylation licenses RIPK1 kinase activity to induce downstream cell death signaling and inflammation, suggesting that S166 phosphorylation can serve as a reliable biomarker for RIPK1 kinase-dependent pathologies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Laurien, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nagata, MasahiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuenke, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delanghe, TomUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiederstein, Janica L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kumari, SnehlataUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarzer, RobinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corona, TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertrand, Mathieu J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kondylis, VangelisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
URN: urn:nbn:de:hbz:38-337367
DOI: 10.1038/s41467-020-15466-8
Journal or Publication Title: Nat. Commun.
Volume: 11
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEPATOCELLULAR-CARCINOMA; NEMO/IKK-GAMMA; NECROPTOSIS; ACTIVATION; MICE; PHOSPHORYLATION; EXPRESSION; STEATOHEPATITIS; HOMEOSTASIS; APOPTOSISMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33736

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