CD95 stimulation results in the formation of a novel death effector domain protein-containing complex.
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.
Lavrik
Inna N
IN
Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Mock
Thomas
T
Golks
Alexander
A
Hoffmann
Julia C
JC
Baumann
Simone
S
Krammer
Peter H
PH
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism* / Q000494:pharmacology; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D019014:fas Receptor / Q000819:agonists / Q000378:metabolism*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; C505533:FADD protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D046912:Multiprotein Complexes; D020033:Protein Isoforms; D019014:fas Receptor; D053181:Caspase 8