Control of death-associated protein kinase (DAPK) activity by phosphorylation and proteasomal degradation

Yijun Jin, Emily K. Blue, Patricia J. Gallagher

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Activation of death-associated protein kinase (DAPK) occurs via dephosphorylation of Ser-308 and subsequent association of calcium/calmodulin. In this study, we confirmed the existence of the alternatively spliced human DAPK-β, and we examined the levels of DAPK autophosphorylation and DAPK catalytic activity in response to tumor necrosis factor or ceramide. It was found that DAPK is rapidly dephosphorylated in response to tumor necrosis factor or ceramide and then subsequently degraded via proteasome activity. Dephosphorylation and activation of DAPK are shown to temporally precede its subsequent degradation. This results in an initial increase in kinase activity followed by a decrease in DAPK expression and activity. The decline in DAPK expression is paralleled with increased caspase activity and cell apoptosis. These results suggest that the apoptosis regulatory activities mediated by DAPK are controlled both by phosphorylation status and protein stability.

Original languageEnglish (US)
Pages (from-to)39033-39040
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number51
DOIs
StatePublished - Dec 22 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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