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Related Experiment Video

Updated: Jul 18, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

CD95 tyrosine phosphorylation is required for CD95 oligomerization.

Andrea Eberle¹, Roland Reinehr, Stephan Becker

¹Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, D-40225 Düsseldorf, Germany.

Apoptosis : an International Journal on Programmed Cell Death

|December 30, 2006

Summary

Proapoptotic stimuli trigger epidermal growth factor receptor (EGFR)-catalyzed CD95 tyrosine phosphorylation, which is essential for CD95 receptor oligomerization and subsequent apoptosis. This phosphorylation event is critical for CD95 receptor translocation and death-inducing signaling complex formation.

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Area of Science:

Cell Biology
Molecular Biology
Biochemistry

Background:

Proapoptotic stimuli like CD95 ligand and bile acids induce epidermal growth factor receptor (EGFR)-catalyzed tyrosine phosphorylation of the CD95 death receptor in hepatocytes.
This phosphorylation is a prerequisite for CD95 translocation, death-inducing signaling complex formation, and apoptotic cell death.
The precise molecular role of CD95 tyrosine phosphorylation in these processes remained unclear.

Purpose of the Study:

To elucidate the molecular role of CD95 tyrosine phosphorylation in the context of apoptosis.
To investigate the requirement of CD95 tyrosine phosphorylation for CD95 receptor oligomerization and translocation.

Main Methods:

Fluorescence resonance energy transfer (FRET) analysis in Huh7 hepatoma cells and mouse embryonic fibroblasts.
Co-transfection with CD95-YFP/CD95-CFP constructs and CD95 mutant variants (CD95(Y232,291F)).
Stimulation with CD95 ligand, proapoptotic bile acids, hyperosmolarity, and epidermal growth factor (EGF).
Inhibition studies using AG1478 and JNK-inhibitory peptide.

Main Results:

CD95 tyrosine phosphorylation is required for CD95 receptor oligomerization, as demonstrated by FRET analysis.
EGFR-catalyzed CD95 tyrosine phosphorylation precedes CD95 oligomerization and translocation to the plasma membrane.
EGFR and CD95 receptor interactions differ depending on the stimulus: EGF induces EGFR homodimerization, while CD95 ligand induces EGFR/CD95 heterodimerization.

Conclusions:

EGFR-catalyzed CD95 tyrosine phosphorylation is a critical step for CD95 receptor oligomerization.
This oligomerization is essential for the translocation of the CD95 receptor complex to the plasma membrane and the subsequent induction of apoptosis.
The findings highlight a novel mechanism linking EGFR signaling to CD95-mediated apoptosis.