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Bidirectional signals transduced by DAPK–ERK interaction promote the apoptotic effect of DAPK
Author(s) -
Chen ChunHau,
Wang WonJing,
Kuo JeanCheng,
Tsai HsiaoChien,
Lin JiaRen,
Chang ZeeFen,
Chen RueyHwa
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600510
Subject(s) - traditional chinese medicine , library science , medicine , traditional medicine , alternative medicine , pathology , computer science
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.