Universität zu Köln

Laurien, Lucie, Nagata, Masahiro, Schuenke, Hannah, Delanghe, Tom, Wiederstein, Janica L., Kumari, Snehlata, Schwarzer, Robin, Corona, Teresa, Krueger, Marcus ORCID: 0000-0003-2008-4582, 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

Full text not available from this repository.

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:	Creators Email ORCID ORCID Put Code Laurien, Lucie UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagata, Masahiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuenke, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Delanghe, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiederstein, Janica L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kumari, Snehlata UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarzer, Robin UNSPECIFIED UNSPECIFIED UNSPECIFIED Corona, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Bertrand, Mathieu J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kondylis, Vangelis UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATOCELLULAR-CARCINOMA; NEMO/IKK-GAMMA; NECROPTOSIS; ACTIVATION; MICE; PHOSPHORYLATION; EXPRESSION; STEATOHEPATITIS; HOMEOSTASIS; APOPTOSIS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/33736