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The role of receptor internalization in CD95 signaling.

ABSTRACT: 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-kappaB 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.

SUBMITTER: Lee KH

PROVIDER: S-EPMC1409734 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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The role of receptor internalization in CD95 signaling.

Lee Kyeong-Hee KH Feig Christine C Tchikov Vladimir V Schickel Robert R Hallas Cora C Schütze Stefan S Peter Marcus E ME Chan Andrew C AC

The EMBO journal 20060223 5

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 compartmen ...[more]

PMID: 16498403

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