期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 17, 页码 17371-17379出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M412449200
关键词
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Monocytes are central components of the innate immune response and normally circulate for a short period of time before undergoing spontaneous apoptosis. During inflammation, differentiation, or oncogenic transformation, the life span of monocytes is prolonged by preventing the activation of the apoptotic program. Here we showed that caspase-3, a cysteine protease required for monocyte apoptosis, is a phosphoprotein. We identified protein kinase C delta (PKC delta) as a member of the protein kinase C family that associates with and phosphorylates caspase-3. The PKC delta-dependent phosphorylation of caspase-3 resulted in an increase in the activity of caspase-3. This effect of PKC delta is specific to caspase-3, as evidenced by the absence of similar effects on caspase-9. The activity of PKC delta precedes the activation of caspase-3 during spontaneous monocyte apoptosis and in monocyte-induced apoptosis. We found that the overexpression of PKC delta resulted in an increase of apoptosis, whereas its inhibition blocked caspase-3 activity and decreased apoptosis. Our results provided evidence that the PKC delta-dependent phosphorylation of caspase-3 provided a novel pro-apoptotic mechanism involved in the regulation of monocyte life span.
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