Control of death-associated protein kinase (DAPK) activity by phosphorylation and proteasomal degradation.
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-beta, 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.
Jin
Yijun
Y
Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, Louisiana 71103, USA.
Blue
Emily K
EK
Gallagher
Patricia J
PJ
D000469:Alkaline Phosphatase / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D064550:Death-Associated Protein Kinases; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D048069:Tumor Necrosis Factors / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D048069:Tumor Necrosis Factors; D012694:Serine; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000469:Alkaline Phosphatase; D020169:Caspases; D046988:Proteasome Endopeptidase Complex