Publikation: Fas-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway
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Fas receptor-induced apoptosis plays critical roles in immune homeostasis. However, most of the signal transduction events distal to Fas ligatlon have not been elucidated. Here, we show that Ras is activated following ligation of Fas on lymphoid lines. The activation of Ras is a critical component of this apoptotic pathway, since Inhibition of Ras by neutralizing antibody or a dominant-negative Ras mutant interfered with Fas-induced apoptosis. Furthermore, ligatlon of Fas also resulted in stimulation of the sphingomyelin signaling pathway to produce ceramides, which, in turn, are capable of inducing both Ras activation and apoptosis. This suggests that ceramides acts as second messengers in Fas signaling via Ras. Thus, ligation of the Fas molecule on lymphocyte lines induces activation of Ras via the action of ceramide, and this activation is necessary, but not sufficient, for subsequent apoptosis.
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GULBINS, Erich, Reid BISSONNETTE, Artin MAHBOUBI, Seamus MARTIN, Walter NISHLOKA, Thomas BRUNNER, Gottfried BAIER, Gabriele BALER-BLTTERLICH, Cynthia BYRD, Florian LANG, Richard KOLESNICK, Amnon ALTMAN, Douglas GREEN, 1995. Fas-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway. In: Immunity. 1995, 2(4), pp. 341-351. ISSN 1074-7613. Available under: doi: 10.1016/1074-7613(95)90142-6BibTex
@article{Gulbins1995Fasin-14325, year={1995}, doi={10.1016/1074-7613(95)90142-6}, title={Fas-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway}, number={4}, volume={2}, issn={1074-7613}, journal={Immunity}, pages={341--351}, author={Gulbins, Erich and Bissonnette, Reid and Mahboubi, Artin and Martin, Seamus and Nishloka, Walter and Brunner, Thomas and Baier, Gottfried and Baler-Bltterlich, Gabriele and Byrd, Cynthia and Lang, Florian and Kolesnick, Richard and Altman, Amnon and Green, Douglas} }
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