Death-associated protein kinase-mediated cell death modulated by interaction with DANGER.
Death-associated protein kinase-mediated cell death modulated by interaction with DANGER.
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DOI：
10.1523/jneurosci.3974-09.2010
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发表时间：
2010-01-06
期刊：
影响因子：
--
通讯作者：
Snyder SH
中科院分区：
文献类型：
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作者：
Kang BN;Ahmad AS;Saleem S;Patterson RL;Hester L;Doré S;Snyder SH
死亡相关蛋白激酶（DAPK）是多种细胞死亡信号通路中的关键参与者。我们报告说，DAPK的调节危险，部分MAB-21域含有蛋白质。DANGER直接与DAPK结合并抑制DAPK催化活性。与野生型对照细胞相比，DANGER缺陷小鼠胚胎成纤维细胞和神经元表现出更大的DAPK活性和对细胞死亡刺激的敏感性增加。此外，DANGER缺陷小鼠在急性兴奋毒性和短暂脑缺血后表现出比对照小鼠更严重的脑损伤。因此，DANGER可能在生理上调节神经元的活力，并代表中风和神经退行性疾病的潜在治疗靶点。
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 exitotoxicity 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.