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 (Ca2+), 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. Antioxid. Redox Signal. 13, 1051–1085. Introduction The PKC family: Members, structure, and activators ROS regulating pathways in the cell and relationship with PKC and disease The intracellular distribution of PKC is sensitive to redox changes Involvement of PKCs in Neoplastic Transformation Altered PKC expression in cancer PKCs and cell-cycle regulation PKC Family as Key Player in the Apoptotic Process Role of PKC in the Autophagy Process PKC Isoforms as Aging Actors PKCs as a Rheostat in Neurosurvival and Death PKCɛ and δ: Role in Ischemic Preconditioning and Ischemia/Reperfusion Injury PKC in Diabetes PKC and Calcium The PKC–ROS Interplay in the Hormone-Signaling Pathway Angiotensin II Thyroid hormones Leptin Mesenchymal Stem Cell Differentiation: PKCs and Oxidative Stress Adipocyte differentiation Osteogenic differentiation Conclusions