PMID- 9830064
OWN - NLM
STAT- MEDLINE
DCOM- 19990108
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 49
DP  - 1998 Dec 4
TI  - TRAIL/Apo2L activates c-Jun NH2-terminal kinase (JNK) via caspase-dependent and 
      caspase-independent pathways.
PG  - 33091-8
AB  - In this study we show that TRAIL (tumor necrosis factor-related 
      apoptosis-inducing ligand), also called Apo2L, activates the c-Jun N-terminal 
      kinase (JNK). Interestingly, TRAIL-induced JNK activation occurs in a cell 
      type-specific manner. In HeLa cells, TRAIL-induced JNK activation can be 
      completely blocked with the cysteine protease inhibitor zVAD-fmk, whereas the 
      same inhibitor has no, or even a stimulatory, effect on JNK activation in Kym-1 
      cells. Hence, TRAIL can engage at least two independent pathways leading to JNK 
      activation, one that is cysteine protease-dependent and one that is cysteine 
      protease-independent. To investigate whether the cysteine protease-dependent 
      signaling of TRAIL leading to JNK activation is related to the apoptotic pathway 
      engaged by this ligand, we investigated HeLa cells stably overexpressing a 
      dominant negative mutant of FADD (Fas-associating protein with death domain) 
      (GFP(green fluorescent protein)DeltaFADD). In these cells, TRAIL-induced cell 
      death and activation of the apoptosis executioner caspase-8 (FLICE/MACH) and 
      caspase-3 (YAMA, CPP-32, Apopain), that belong to caspase subfamily of cysteine 
      proteases, were abrogated, whereas JNK activation remained unaffected and was 
      still sensitive toward z-VAD-fmk. Similar data were found in HeLa cells 
      overexpressing Apo1/Fas and GFPDeltaFADD upon stimulation with agonistic 
      antibodies. These data suggest that cross-linking of the TRAIL receptors and 
      Apo1/Fas, respectively, engages a FADD-dependent pathway leading to the 
      activation of apoptotic caspases and, in parallel, a FADD-independent pathway 
      leading to the stimulation of one or more cysteine proteases capable to activate 
      JNK but not sufficient for the induction of cell death.
FAU - Muhlenbeck, F
AU  - Muhlenbeck F
AD  - Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 
      31, 70569 Stuttgart, Germany.
FAU - Haas, E
AU  - Haas E
FAU - Schwenzer, R
AU  - Schwenzer R
FAU - Schubert, G
AU  - Schubert G
FAU - Grell, M
AU  - Grell M
FAU - Smith, C
AU  - Smith C
FAU - Scheurich, P
AU  - Scheurich P
FAU - Wajant, H
AU  - Wajant H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis Regulatory Proteins
MH  - Base Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Caspase 3
MH  - Caspases/*metabolism
MH  - Cell Line
MH  - DNA Primers
MH  - Enzyme Activation
MH  - HeLa Cells
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Membrane Glycoproteins/*metabolism
MH  - *Mitogen-Activated Protein Kinases
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 1998/11/26 00:00
MHDA- 1998/11/26 00:01
CRDT- 1998/11/26 00:00
PHST- 1998/11/26 00:00 [pubmed]
PHST- 1998/11/26 00:01 [medline]
PHST- 1998/11/26 00:00 [entrez]
AID - S0021-9258(19)58987-6 [pii]
AID - 10.1074/jbc.273.49.33091 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Dec 4;273(49):33091-8. doi: 10.1074/jbc.273.49.33091.