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

Bingnan N. Kang, Abdullah S. Ahmad, Sofiyan Saleem, Randen L. Patterson, Lynda Hester, Sylvain Doré, Solomon H. Snyder

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalJournal of Neuroscience
Volume30
Issue number1
DOIs
StatePublished - Jan 6 2010

ASJC Scopus subject areas

  • Neuroscience(all)

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