Mitogen-activated protein kinase-mediated Fas apoptotic signaling pathway
Open Access
- 1 April 1997
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 94 (7), 3302-3307
- https://doi.org/10.1073/pnas.94.7.3302
Abstract
Ligation of the cell surface receptor Fas/APO-1 (CD95) by its specific ligand or by anti-Fas antibodies rapidly induces apoptosis in susceptible cells. To characterize the molecular events involved in Fas-induced apoptosis, we examined the contribution of two subgroups of the mitogen-activated protein (MAP) kinase family, the Jun kinases or stress-activated protein kinases (JNKs/SAPKs) and the extracellular signal-regulated kinases (ERKs), in a Fas-sensitive neuroblastoma cell line. Here we show that both JNK and ERK protein kinases were activated upon Fas crosslinking through a Ras-dependent mechanism. Interference with either the JNK or ERK pathway by ectopic expression of dominant-interfering mutant proteins blocked Fas-mediated apoptosis. ERK activation was transient and associated with induced expression of the Fas receptor. In contrast, JNK activation was sustained and correlated with the onset of apoptosis. These data indicate that the ERK and the JNK groups of MAP kinases cooperate in the induction of cell death by Fas. Inhibition of Fas killing by an interleukin 1β-converting enzyme (ICE)-like protease inhibitor peptide did not modify Fas-induced JNK activation upon Fas ligation. In contrast, changes in Bcl-2 level due to expression of sense and antisense vectors influenced the sensitivity to Fas killing and Fas-induced JNK activation.Keywords
This publication has 69 references indexed in Scilit:
- Persistent Activation of c-Jun N-terminal Kinase 1 (JNK1) in γ Radiation-induced ApoptosisJournal of Biological Chemistry, 1996
- Fas(CD95)/FasL interactions required for programmed cell death after T-cell activationNature, 1995
- Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomasNature, 1995
- MAPKs: new JNK expands the groupTrends in Biochemical Sciences, 1994
- Transformation of Mammalian Cells by Constitutively Active MAP Kinase KinaseScience, 1994
- Fas and Perforin Pathways as Major Mechanisms of T Cell-Mediated CytotoxicityScience, 1994
- Oncogenes and cell deathCurrent Opinion in Genetics & Development, 1994
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993
- Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3Cell, 1993
- Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around Jh on chromosome 14 and near a transcriptional unit on 18Cell, 1985