JNK Phosphorylation and Activation of BAD Couples the Stress-activated Signaling Pathway to the Cell Death Machinery

The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in mediating apoptosis in the developing and mature organism. The JNK signaling pathway is thought to induce apoptosis via transcription-dependent and transcription-independent mechanisms that remain to be elucidated. In this...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-10, Vol.277 (43), p.40944-40949
Main Authors: Donovan, Nicole, Becker, Esther B E, Konishi, Yoshiyuki, Bonni, Azad
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Apoptosis
bcl-Associated Death Protein
Carrier Proteins - chemistry
Carrier Proteins - metabolism
Cell Line
JNK Mitogen-Activated Protein Kinases
Mice
Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
Serine - metabolism
Signal Transduction
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Summary:The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in mediating apoptosis in the developing and mature organism. The JNK signaling pathway is thought to induce apoptosis via transcription-dependent and transcription-independent mechanisms that remain to be elucidated. In this study, we report a novel mechanism by which the JNK signaling pathway directly activates a component of the cell death machinery. We have found that JNK catalyzes the phosphorylation of the BH3-only protein BAD at the distinct site of serine 128 in vitro . Activation of the JNK signaling pathway induces the BAD serine 128 phosphorylation in vivo , including in primary granule neurons of the developing rat cerebellum. The JNK-induced BAD serine 128 phosphorylation promotes the apoptotic effect of BAD in primary neurons by antagonizing the ability of growth factors to inhibit BAD-mediated apoptosis. These findings indicate that BAD is a novel substrate of JNK that links the stress-activated signaling pathway to the cell death machinery.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M206113200