JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery

被引:214
作者
Donovan, N [1 ]
Becker, EBE [1 ]
Konishi, Y [1 ]
Bonni, A [1 ]
机构
[1] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Dept Pathol, Boston, MA 02115 USA
关键词
D O I
10.1074/jbc.M206113200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:40944 / 40949
页数:6
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