Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK
Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK
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DOI：
10.1038/sj.emboj.7600510
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发表时间：
2005-01-26
期刊：
影响因子：
11.4
通讯作者：
Chen, RH
中科院分区：
文献类型：
--
作者：
Chen, CH;Wang, WJ;Chen, RH
死亡相关蛋白激酶（DAPK）是一种含有死亡结构域的丝氨酸/苏氨酸激酶，参与多种凋亡模式。在这里，我们确定细胞外信号调节激酶（ERK）作为DAPK相互作用蛋白。DAPK通过其死亡结构域内的对接序列与ERK相互作用，并且是ERK的底物。ERK在Ser 735处磷酸化DAPK增加了DAPK在体外和体内的催化活性。相反，DAPK促进ERK的细胞质滞留，从而抑制细胞核中的ERK信号传导。DAPK和ERK之间的这种相互调节构成了一个正反馈回路，最终促进DAPK的凋亡活性。在ERK-DAPK相互作用增强的生理性细胞凋亡系统中，ERK或DAPK的下调抑制了这种细胞凋亡。这些结果表明，DAPK和ERK之间的双向信号可能有助于DAPK的死亡结构域的促凋亡功能。
Death-associated protein kinase ( DAPK) is a death domain-containing serine/threonine kinase, and participates in various apoptotic paradigms. Here, we identify the extracellular signal-regulated kinase (ERK) as a DAPK-interacting protein. DAPK interacts with ERK through a docking sequence within its death domain and is a substrate of ERK. Phosphorylation of DAPK at Ser 735 by ERK increases the catalytic activity of DAPK both in vitro and in vivo. Conversely, DAPK promotes the cytoplasmic retention of ERK, thereby inhibiting ERK signaling in the nucleus. This reciprocal regulation between DAPK and ERK constitutes a positive feedback loop that ultimately promotes the apoptotic activity of DAPK. In a physiological apoptosis system where ERK-DAPK interplay is reinforced, downregulation of either ERK or DAPK suppresses such apoptosis. These results indicate that bidirectional signalings between DAPK and ERK may contribute to the apoptosis-promoting function of the death domain of DAPK.