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Induction of Apoptosis by Protein Kinase Cδ Is Independent of Its Kinase Activity

2002; Elsevier BV; Volume: 277; Issue: 35 Linguagem: Inglês

10.1074/jbc.m203734200

1083-351X

Axel Goerke, Norio Sakai, Elisabeth Gutjahr, Walter A. Schlapkohl, J. Frederic Mushinski, Hermann Haller, Walter Kölch, Naoaki Saito, Harald Mischak,

NF-κB Signaling Pathways

Protein kinase C, a multigene family of phospholipid-dependent and diacylglycerol-activated Ser/Thr protein kinases, is a key component in many signal transduction pathways. The kinase activity was thought to be essential for a plethora of biological processes attributed to these enzymes. Here we show that at least one protein kinase C function, the induction of apoptosis by protein kinase Cδ, is independent of the kinase activity. Stimulation of green fluorescent protein-protein kinase Cδ fusion protein with phorbol ester or diacylglycerol led to its redistribution within seconds after the stimulus. Membrane blebbing, an early hallmark of apoptosis, was visible as early as 20 min after stimulation, and nuclear condensation was visible after 3–5 h. Apoptosis could be inhibited by expression of Bcl-2 but not by specific protein kinase C inhibitors. In addition, a kinase-negative mutant of protein kinase Cδ also induced apoptosis to the same extent as the wild type enzyme. Apoptosis was confined to the protein kinase Cδ-overexpressing cells. Stimulation of overexpressed protein kinase Cε did not result in increased apoptosis. Our results indicate that distinct protein kinase C isozymes induce apoptosis in vascular smooth muscle cells. More importantly, they show that some protein kinase C effector functions are independent of the catalytic activity.