Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins.
Biochem Biophys Res Commun
; 464(1): 70-5, 2015 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-26047703
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Apoptose
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Proteínas 14-3-3
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Proteínas Proto-Oncogênicas c-akt
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Exorribonucleases
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Proteínas Quinases Associadas com Morte Celular
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article