CD95 stimulation results in the formation of a novel death effector domain protein-containing complex |
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Authors: | Lavrik Inna N Mock Thomas Golks Alexander Hoffmann Julia C Baumann Simone Krammer Peter H |
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Institution: | Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. |
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Abstract: | Stimulation of CD95 (APO-1/Fas) by its natural ligand CD95L (APO-1L/FasL) leads to the formation of the death-inducing signaling complex. Here we report that upon CD95 stimulation in several T and B cell lines, a novel signaling complex is formed, which we term complex II. Complex II is composed of the death effector domain proteins as follows: procaspase-8a/b, three isoforms of c-FLIP (c-FLIP(L), c-FLIP(S), c-FLIP(R)), and FADD. Notably, complex II does not contain CD95. Based on our findings we suggest that CD95 signaling includes two steps. The first step involves formation of the death-inducing signaling complex at the cell membrane. The second step involves formation of the cytosolic death effector domain protein-containing complex that may play an important role in amplification of caspase activation. |
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