Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation.

Alanine Transaminase / metabolism Animals Apoptosis Bone Marrow Cells / cytology Colitis / pathology Genotype Hepatitis / pathology Inflammation / metabolism Intracellular Signaling Peptides and Proteins / metabolism Macrophages / metabolism Mice, Inbred C57BL Mutation / genetics Neoplasms / pathology Phosphorylation Phosphoserine / metabolism Receptor-Interacting Protein Serine-Threonine Kinases / metabolism Sepsis / pathology Skin / pathology Tumor Necrosis Factor-alpha

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
08 04 2020
Historique:
received: 22 07 2019
accepted: 12 03 2020
entrez: 10 4 2020
pubmed: 10 4 2020
medline: 28 7 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-15466-8 PMID: 32269263 PMC: PMC7142081
pubmed: 32269263
doi: 10.1038/s41467-020-15466-8
pii: 10.1038/s41467-020-15466-8
pmc: PMC7142081
doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0
NEMO protein, mouse 0
Tumor Necrosis Factor-alpha 0
Phosphoserine 17885-08-4
Alanine Transaminase EC 2.6.1.2
Receptor-Interacting Protein Serine-Threonine Kinases EC 2.7.11.1
Ripk1 protein, mouse EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1747

Références

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Auteurs

Lucie Laurien (L)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Masahiro Nagata (M)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Hannah Schünke (H)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Tom Delanghe (T)

VIB Center for Inflammation Research, Technologiepark-Zwinjaarde 71, 9052, Zwinjaarde-Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Technologiepark-Zwinjaarde 71, 9052, Zwinaarde-Ghent, Belgium.

Janica L Wiederstein (JL)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Snehlata Kumari (S)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
ORCID: 0000-0002-4971-3162

Robin Schwarzer (R)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Teresa Corona (T)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Marcus Krüger (M)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
ORCID: 0000-0002-5846-6941

Mathieu J M Bertrand (MJM)

VIB Center for Inflammation Research, Technologiepark-Zwinjaarde 71, 9052, Zwinjaarde-Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Technologiepark-Zwinjaarde 71, 9052, Zwinaarde-Ghent, Belgium.
ORCID: 0000-0001-9000-0626

Vangelis Kondylis (V)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
ORCID: 0000-0002-6970-8731

Manolis Pasparakis (M)

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. pasparakis@uni-koeln.de.
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany. pasparakis@uni-koeln.de.
ORCID: 0000-0002-9870-0966

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Nitrogenous group transferases › Transaminases › Alanine transaminase › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Eucaryotes › Animaux › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du côlon › Colite › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Hépatite › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Tumeurs › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Métabolisme › Phosphorylation › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides phosphoaminés › Phosphosérine › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Receptor-Interacting Protein Serine-Threonine Kinases › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Sepsie › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Système tégumentaire › Peau › Autophosphorylation at serine 166 regulates...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Autophosphorylation at serine 166 regulates...