1. Academic Validation
  2. 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

  • EMBO J. 2005 Jan 26;24(2):294-304. doi: 10.1038/sj.emboj.7600510.
Chun-Hau Chen 1 Won-Jing Wang Jean-Cheng Kuo Hsiao-Chien Tsai Jia-Ren Lin Zee-Fen Chang Ruey-Hwa Chen
Affiliations

Affiliation

  • 1 Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract

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.

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