The role of receptor internalization in CD95 signaling

Kyeong Hee Lee, Christine Feig, Vladimir Tchikov, Robert Schickel, Cora Hallas, Stefan Schütze, Marcus E. Peter, Andrew C. Chan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


Activation of the cell surface CD95 receptor triggers a cascade of signaling events, including assembly of the death-inducing signaling complex (DISC), that culminate in cellular apoptosis. In this study, we demonstrate a general requirement of receptor internalization for CD95 ligand-mediated DISC amplification, caspase activation and apoptosis in type I cells. Recruitment of DISC components to the activated receptor predominantly occurs after the receptor has moved into an endosomal compartment and blockade of CD95 internalization impairs DISC formation and apoptosis. In contrast, CD95 ligand stimulation of cells unable to internalize CD95 results in activation of proliferative Erk and NF-κB signaling pathways. Hence, the subcellular localization and internalization pathways of CD95 play important roles in controlling activation of distinct signaling cascades to determine divergent cellular fates.

Original languageEnglish (US)
Pages (from-to)1009-1023
Number of pages15
JournalEMBO Journal
Issue number5
StatePublished - Mar 8 2006


  • Endosomes
  • Signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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