EMBO J. 2006 Mar 8;25(5):1009-23. Epub 2006 Feb 23.

The role of receptor internalization in CD95 signaling.External

Lee, K. H., Feig, C., Tchikov, V., Schickel, R., Hallas, C., Schutze, S., Peter, M. E., Chan, A. C.,
--- - Department of Immunology, Genentech Inc., South San Francisco, CA 94080, USA.
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.
PMID: 16498403External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link Fas Co-Immunofluorescence staining BJAB Not specified Not specified Not specified Not specified 16498403
DD FADD Link Fas Co-immunoprecipitation SKW6.4 16498403
(Link: click this icon to show interactions only between the two corresponding DDs)