Redox control of protein kinase C: cell- and disease-specific aspects.
Hormones, growth factors, electrical stimulation, and cell-cell interactions regulate numerous cellular processes by altering the levels of second messengers, thus influencing biochemical reactions inside the cells. The Protein Kinase C family (PKCs) is a group of serine/threonine kinases that are dependent on calcium (Ca(2+)), diacylglycerol, and phospholipids. Signaling pathways that induce variations on the levels of PKC activators have been implicated in the regulation of diverse cellular functions and, in turn, PKCs are key regulators of a plethora of cellular processes, including proliferation, differentiation, and tumorigenesis. Importantly, PKCs contain regions, both in the N-terminal regulatory domain and in the C-terminal catalytic domain, that are susceptible to redox modifications. In several pathophysiological conditions when the balance between oxidants, antioxidants, and alkylants is compromised, cells undergo redox stress. PKCs are cell-signaling proteins that are particularly sensitive to redox stress because modification of their redox-sensitive regions interferes with their activity and, thus, with their biological effects. In this review, we summarize the involvement of PKCs in health and disease and the importance of redox signaling in the regulation of this family of kinases.
Giorgi
Carlotta
C
Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation (ICSI), BioPharmaNet, University of Ferrara, Ferrara, Italy.
Agnoletto
Chiara
C
Baldini
Claudio
C
Bononi
Angela
A
Bonora
Massimo
M
Marchi
Saverio
S
Missiroli
Sonia
S
Patergnani
Simone
S
Poletti
Federica
F
Rimessi
Alessandro
A
Zavan
Barbara
B
Pinton
Paolo
P
D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D003920:Diabetes Mellitus / Q000201:enzymology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D009369:Neoplasms / Q000201:enzymology* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D011493:Protein Kinase C; D002118:Calcium