Role of proteolytic activation of protein kinase Cdelta in oxidative stress-induced apoptosis.
Protein kinase Cdelta (PKCdelta), a member of the novel PKC family, is emerging as a redox-sensitive kinase in various cell types. Oxidative stress activates the PKCdelta kinase by translocation, tyrosine phosphorylation, or proteolysis. During proteolysis, caspase-3 cleaves the native PKCdelta (72-74 kDa) into 41-kDa catalytically active and 38-kDa regulatory fragments to persistently activate the kinase. The proteolytic activation of PKCdelta plays a key role in promoting apoptotic cell death in various cell types, including neuronal cells. Attenuation of PKCdelta proteolytic activation by antioxidants suggests that the cellular redox status can influence activation of the proapoptotic kinase. PKCdelta may also amplify apoptotic signaling via positive feedback activation of the caspase cascade. Thus, the dual role of PKCdelta 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.
Parkinson's Disorders Research Program, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA. akanthas@iastate.edu
Anumantha G
AG
Kanthasamy
Masashi
M
Kitazawa
Arthi
A
Kanthasamy
Vellareddy
V
Anantharam
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000201:enzymology / Q000503:physiopathology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D021381:Protein Transport / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000502:physiology
C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D017027:Protein Tyrosine Phosphatases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases