title: Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins.
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.
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan. Electronic address: kyuasa@tokushima-u.ac.jp.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yuasa
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Ota
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Kinuka
authors.initials: K
authors.lastname: Isshiki
authors.affiliation: Department of Infectious Medicine, Division of Eukaryotic Microbiology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Biological Science and Technology, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D019556:COS Cells; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D064550:Death-Associated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D013912:Threonine; D064550:Death-Associated Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; C579103:dapk2 protein, mouse; D005095:Exoribonucleases; C413442:SFN protein, human; D019703:Calcineurin
keywords: 14-3-3; Akt; Apoptosis; DAPK2