DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress.

Article Details

Citation

Eisenberg-Lerner A, Kimchi A

DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress.

Cell Death Differ. 2007 Nov;14(11):1908-15. Epub 2007 Aug 17.

PubMed ID
17703233 [ View in PubMed
]
Abstract

The stress-activated kinase JNK mediates key cellular responses to oxidative stress. Here we show that DAP kinase (DAPk), a cell death promoting Ser/Thr protein kinase, plays a main role in oxidative stress-induced JNK signaling. We identify protein kinase D (PKD) as a novel substrate of DAPk and demonstrate that DAPk physically interacts with PKD in response to oxidative stress. We further show that DAPk activates PKD in cells and that induction of JNK phosphorylation by ectopically expressed DAPk can be attenuated by knocking down PKD expression or by inhibiting its catalytic activity. Moreover, knockdown of DAPk expression caused a marked reduction in JNK activation under oxidative stress, indicating that DAPk is indispensable for the activation of JNK signaling under these conditions. Finally, DAPk is shown to be required for cell death under oxidative stress in a process that displays the characteristics of caspase-independent necrotic cell death. Taken together, these findings establish a major role for DAPk and its specific interaction with PKD in regulating the JNK signaling network under oxidative stress.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Death-associated protein kinase 1P53355Details
Serine/threonine-protein kinase D1Q15139Details