Universität zu Köln

Polykratis, Apostolos ORCID: 0000-0001-6720-3302, Hermance, Nicole, Zelic, Matija, Roderick, Justine, Kim, Chun ORCID: 0000-0001-9497-708X, Lee, Thomas H., Chan, Francis K. M., Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Kelliher, Michelle A. (2014). Cutting Edge: RIPK1 Kinase Inactive Mice Are Viable and Protected from TNF-Induced Necroptosis In Vivo. J. Immunol., 193 (4). S. 1539 - 1544. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

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Abstract

The serine/threonine kinase RIPK1 is recruited to TNFR1 to mediate proinflammatory signaling and to regulate TNF-induced cell death. A RIPK1 deficiency results in perinatal lethality, impaired NF kappa B and MAPK signaling, and sensitivity to TNF-induced apoptosis. Chemical inhibitor and in vitro-reconstitution studies suggested that RIPK1 displays distinct kinase activity-dependent and -independent functions. To determine the contribution of RIPK1 kinase to inflammation in vivo, we generated knock-in mice endogenously expressing catalytically inactive RIPK1 D138N. Unlike Ripk1(-/-) mice, which die shortly after birth, Ripk1(D138N/D138N) mice are viable. Cells expressing RIPK1 D138N are resistant to TNF- and polyinosinic-polycytidylic acid-induced necroptosis in vitro, and Ripk1(D138N/D138N) mice are protected from TNF-induced shock in vivo. Moreover, Ripk1(D138N/D138N) mice fail to control vaccinia virus replication in vivo. This study provides genetic evidence that the kinase activity of RIPK1 is not required for survival but is essential for TNF-, TRIF-, and viral-initiated necroptosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Polykratis, Apostolos UNSPECIFIED orcid.org/0000-0001-6720-3302 UNSPECIFIED Hermance, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Zelic, Matija UNSPECIFIED UNSPECIFIED UNSPECIFIED Roderick, Justine UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Chun UNSPECIFIED orcid.org/0000-0001-9497-708X UNSPECIFIED Lee, Thomas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chan, Francis K. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Kelliher, Michelle A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-431967
DOI:	10.4049/jimmunol.1400590
Journal or Publication Title:	J. Immunol.
Volume:	193
Number:	4
Page Range:	S. 1539 - 1544
Date:	2014
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	1550-6606
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 PROGRAMMED NECROSIS; ACTIVATION; DOMAIN; UBIQUITINATION; APOPTOSIS; CLEAVAGE Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/43196