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Death-associated protein kinase-mediated cell death modulated by interaction with DANGER.

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. DANGER binds directly to DAPK and inhibits DAPK catalytic activity. DANGER-deficient 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.

SUBMITTER: Kang BN

PROVIDER: S-EPMC2840720 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Death-associated protein kinase-mediated cell death modulated by interaction with DANGER.

Kang Bingnan N BN Ahmad Abdullah S AS Saleem Sofiyan S Patterson Randen L RL Hester Lynda L Doré Sylvain S Snyder Solomon H SH

The Journal of neuroscience : the official journal of the Society for Neuroscience 20100101 1

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. DANGER binds directly to DAPK and inhibits DAPK catalytic activity. DANGER-deficient 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 acu ...[more]

PMID: 20053891

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