Death-associated protein kinase-mediated cell death modulated by interaction with DANGER.
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.
Kang
Bingnan N
BN
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Ahmad
Abdullah S
AS
Saleem
Sofiyan
S
Patterson
Randen L
RL
Hester
Lynda
L
Doré
Sylvain
S
Snyder
Solomon H
SH
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D064550:Death-Associated Protein Kinases; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C516570:ITPRIP protein, human; D008565:Membrane Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases