2. Academic Validation
  3. Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins

Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins

  • Biochem Biophys Res Commun. 2015 Aug 14;464(1):70-5. doi: 10.1016/j.bbrc.2015.05.105.
Keizo Yuasa 1,  Reina Ota 2,  Shinya Matsuda 2,  Kinuka Isshiki 2,  Masahiro Inoue 3,  Akihiko Tsuji 2
Affiliations

Affiliations

  • 1 Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan. Electronic address: kyuasa@tokushima-u.ac.jp.
  • 2 Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan.
  • 3 Department of Infectious Medicine, Division of Eukaryotic Microbiology, Kurume University School of Medicine, Kurume, Japan.
PMID: 26047703 DOI: 10.1016/j.bbrc.2015.05.105
Abstract

Death-associated protein kinase 2 (DAPK2), a CA(2+)/calmodulin-regulated serine/threonine kinase, induces Apoptosis. However, the signaling mechanisms involved in this process are unknown. Using a proteomic approach, we identified 14-3-3 proteins as novel DAPK2-interacting proteins. The 14-3-3 family has the ability to bind to phosphorylated proteins via recognition of three conserved amino acid motifs (mode 1-3 motifs), and DAPK2 contains the mode 3 motif ((pS/pT)X1-2-COOH). The interaction of 14-3-3 proteins with DAPK2 was dependent on the phosphorylation of Thr(369), and effectively suppressed DAPK2 kinase activity and DAPK2-induced Apoptosis. Furthermore, we revealed that the 14-3-3 binding site Thr(369) of DAPK2 was phosphorylated by the survival kinase Akt. Our findings suggest that DAPK2-induced Apoptosis is negatively regulated by Akt and 14-3-3 proteins.

Keywords

14-3-3; Akt; Apoptosis; DAPK2.

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