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- Title
Death-Associated Protein Kinase-Mediated Cell Death Modulated by Interaction with DANGER.
- Authors
Kang, Bingnan N.; Ahmad, Abdullah S.; Saleem, Sofiyan; Patterson, Randen L.; Hester, Lynda; Doré, Sylvain; Snyder, Solomon H.
- Abstract
Death-associated protein kinase (DAPK) is a key player in multiple cell death signaling pathways. We report that DAPK is regulated by DANGER, a partial MAB-21 domain-containing protein.DANGERbinds directly toDAPKand inhibitsDAPKcatalytic activity. DANGERdeficient mouse embryonic fibroblasts and neurons exhibit greater DAPK activity and increased sensitivity to cell death stimuli than do wild-type control cells. In addition, DANGER-deficient mice manifest more severe brain damage after acute excitotoxicity and transient cerebral ischemia than do control mice. Accordingly, DANGER may physiologically regulate the viability of neurons and represent a potential therapeutic target for stroke and neurodegenerative diseases.
- Subjects
PROTEIN kinases; CELL death; PROTEIN-protein interactions; NEURAL pathways; NEURAL transmission; FIBROBLASTS; BRAIN damage; NEURODEGENERATION
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 1, p93
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3974-09.2010