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  • The EMBO Journal (2005) 24, 294 - 304
  • doi:10.1038/sj.emboj.7600510

Published online: 16 December 2004

Bidirectional signals transduced by DAPK–ERK interaction promote the apoptotic effect of DAPK

Chun-Hau Chen1, Won-Jing Wang1, Jean-Cheng Kuo1, Hsiao-Chien Tsai1, Jia-Ren Lin1, Zee-Fen Chang2 and Ruey-Hwa Chen1

  1. Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
  2. Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan

Correspondence to:

Ruey-Hwa Chen, Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Tel.: +886 2 231 234 56 Ext. 5700; Fax: +886 2 239 578 01; E-mail: rhchen@ha.mc.ntu.edu.tw

Received 21 June 2004; Accepted 19 November 2004

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.

  • Keywords:

    • anoikis,
    • DAPK,
    • death domain,
    • ERK