c-Jun NH2-terminal kinase activation leads to a FADD-dependent but Fas ligand-independent cell death in Jurkat T cells.

Abstract

Persistent c-Jun NH2-terminal kinase (JNK) activation induces cell death. Different mechanisms are ascribed to JNK-induced cell death. Most of the JNK-apoptosis studies employ stress stimuli known to activate kinases other than JNK. Here we used overexpression of mitogen-activated protein kinase kinase 7 (MKK7) to activate selectively JNK in T lymphoma Jurkat cells. Similar to that reported previously, Fas ligand (FasL) expression was up-regulated by JNK activation. Dominant negative-FADD and caspase-8 inhibitor benzyloxycarbonyl-Ile-Glu-Thr-Asp effectively inhibited MKK7-induced cell death, supporting a major involvement of FADD cascade. However, MKK7-induced cell death was not prevented by antagonist antibody ZB4 and Fas-Fc, indicating that Fas-FasL interaction is minimally involved. Confocal microscopy revealed that persistent JNK activation led to clustering of Fas. Our results suggest that, in contrast to that reported previously, JNK alone-induced death in Jurkat cells is FADD-dependent but is not triggered by Fas-FasL interaction.

• Authors: Y Chen, M Z Lai
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 11 Pg. 8350-7 (Mar 16 2001) ISSN: 0021-9258 [Print] United States
• PMID: 11106658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Carrier Proteins
• Caspase Inhibitors
• FADD protein, human
• FASLG protein, human
• Fas Ligand Protein
• Fas-Associated Death Domain Protein
• Membrane Glycoproteins
• Protein Serine-Threonine Kinases
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinase 1
• MAP3K1 protein, human
• MAP Kinase Kinase 7
• MAP2K7 protein, human
• Mitogen-Activated Protein Kinase Kinases
• CASP8 protein, human
• CASP9 protein, human
• Caspase 8
• Caspase 9

Topics

• Adaptor Proteins, Signal Transducing
• Apoptosis
• Carrier Proteins (physiology)
• Caspase 8
• Caspase 9
• Caspase Inhibitors
• Enzyme Activation
• Fas Ligand Protein
• Fas-Associated Death Domain Protein
• Humans
• JNK Mitogen-Activated Protein Kinases
• Jurkat Cells
• MAP Kinase Kinase 7
• MAP Kinase Kinase Kinase 1
• Membrane Glycoproteins (physiology)
• Mitogen-Activated Protein Kinase Kinases (physiology)
• Mitogen-Activated Protein Kinases (physiology)
• Protein Serine-Threonine Kinases (physiology)