Fas ligand-induced c-Jun kinase activation in lymphoid cells requires extensive receptor aggregation but is independent of DAXX, and Fas-mediated cell death does not involve DAXX, RIP, or RAIDD

Jun kinase signaling can be elicited by death receptor activation, but the mechanism and significance of this event are still unclear. It has been rep orted that cross-linking Abs to Fas trigger c-Jun N-terminal kinase (JNK) s ignaling via caspase-mediated activation of MEKK1 (JNK kinase kinase), elev ation of ceramide levels or by recruitment of death domain associated prote in (DAXX) to Fas. The effect of physiological ligand for Fas on JNK signali ng was never investigated, although evidence is accumulating that Fas ligan d is able to induce cellular responses distinct from those evoked by Ab-med iated cross-linking of Fas, Therefore, we investigated the effect of Fas li gand on JNK signaling, Like its ability to induce cell death, Fas ligand re liably activated JNK only upon extensive aggregation of the receptor. Altho ugh this was partially dependent on caspase activation, DAXX was not requir ed. DAXX and other death receptor-associated proteins, which have been repo rted to bind directly or indirectly to Fas, such as receptor interacting pr otein (RIP) and RIP-associated ICH-1/CED-3-homologous protein with a death domain (RAIDD), were shown to be dispensable for Fas ligand-induced apoptos is.