Role of Proteolytic Activation of Protein Kinase Cδ in Oxidative Stress-Induced Apoptosis

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Abstract
Protein kinase Cδ (PKCδ), a member of the novel PKC family, is emerging as a redox-sensitive kinase in various cell types. Oxidative stress activates the PKCδ kinase by translocation, tyrosine phosphorylation, or proteolysis. During proteolysis, caspase-3 cleaves the native PKCδ (72-74 kDa) into 41-kDa catalytically active and 38-kDa regulatory fragments to persistently activate the kinase. The proteolytic activation of PKCδ plays a key role in promoting apoptotic cell death in various cell types, including neuronal cells. Attenuation of PKCδ proteolytic activation by antioxidants suggests that the cellular redox status can influence activation of the proapoptotic kinase. PKCδ may also amplify apoptotic signaling via positive feedback activation of the caspase cascade. Thus, the dual role of PKCδ as a mediator and amplifier of apoptosis may be important in the pathogenesis of major neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, and Huntington disease.