Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins.
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Yuasa K, Ota R, Matsuda S, Isshiki K, Inoue M, Tsuji A
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. Epub 2015 Jun 3.
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- 26047703 [ View in PubMed]
- 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.