Related Experiment Video

Updated: Dec 24, 2025

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

761

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

Lucie Laurien1, Masahiro Nagata1, Hannah Schünke1

  • 1Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

Nature Communications
|April 10, 2020
PubMed

Insights

Receptor interacting protein kinase 1 (RIPK1) autophosphorylation at serine 166 is crucial for RIPK1 kinase-dependent apoptosis, necroptosis, and inflammatory diseases. This S166 phosphorylation acts as a biomarker for RIPK1-driven pathologies.

Area of Science:

  • Molecular biology
  • Cellular signaling
  • Immunology

Background:

  • Receptor interacting protein kinase 1 (RIPK1) is a key regulator of cell death and inflammation.
  • RIPK1 kinase activity is implicated in inflammatory and degenerative diseases.
  • Mechanisms of RIPK1-dependent cell death signaling are not fully understood.

Purpose of the Study:

  • To investigate the role of RIPK1 autophosphorylation in regulating RIPK1 kinase activity.
  • To determine the impact of RIPK1 phosphorylation on apoptosis and necroptosis.
  • To assess the in vivo relevance of RIPK1 phosphorylation in inflammatory pathologies.

Main Methods:

  • Site-directed mutagenesis to study RIPK1 phosphorylation at serine 166 (S166).
  • In vitro kinase assays to measure RIPK1 activity.
  • In vivo mouse models of inflammatory diseases.

Main Results:

  • RIPK1 autophosphorylation at S166 is critical for RIPK1 kinase-dependent apoptosis and necroptosis.
  • S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis in vivo.
  • S166 phosphorylation modulates RIPK1 kinase activation but is insufficient to induce cell death alone.

Conclusions:

  • S166 autophosphorylation licenses RIPK1 kinase activity to induce cell death and inflammation.
  • RIPK1 S166 phosphorylation is a critical event in RIPK1-dependent pathologies.
  • S166 phosphorylation serves as a potential biomarker for RIPK1 kinase-dependent diseases.

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