Dynamics and Membrane Interactions of Protein Kinase C

Igumenova, Tatyana I.

doi:10.1021/acs.biochem.5b00565

Cited by 69 publications

(52 citation statements)

References 143 publications

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“…Binding of Ca 2+ to an Asp-lined binding pocket localizes the domain to the plasma membrane via 1] bridging of the C2-bound Ca 2+ to anionic phospholipids and 2] interaction of a basic face in the C2 domain with phosphatidylinositol-4,5-bisphosphate (PIP 2 ), a lipid localized to plasma membrane (Nalefski E. A. et al 2001; Kohout et al 2002; Corbalan-Garcia et al 2003; Sanchez-Bautista et al 2006; Igumenova 2015; Morales et al 2016). Novel PKC isozymes have a ‘novel’ C2 domain that does not serve as a Ca 2+ or plasma membrane sensor: it lacks acidic residues that coordinate Ca 2+ and basic residues that bind PIP 2 .…”

Section: Pkc Family and Regulationmentioning

confidence: 99%

Protein kinase C: perfectly balanced

Newton

2018

Critical Reviews in Biochemistry and Molecular Biology

238

216

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Protein kinase C (PKC) isozymes belong to a family of Ser/Thr kinases whose activity is governed by reversible release of an autoinhibitory pseudosubstrate. For conventional and novel isozymes, this is effected by binding the lipid second messenger, diacylglycerol, but for atypical PKC isozymes, this is effected by binding protein scaffolds. PKC shot into the limelight following the discovery in the 1980s that the diacylglycerol-sensitive isozymes are ‘receptors’ for the potent tumor-promoting phorbol esters. This set in place a concept that PKC isozymes are oncoproteins. Yet three decades of cancer clinical trials targeting PKC with inhibitors failed and, in some cases, worsened patient outcome. Emerging evidence from cancer-associated mutations and protein expression levels provide a reason: protein kinase C isozymes generally function as tumor suppressors and their activity should be restored, not inhibited, in cancer therapies. And whereas not enough activity is associated with cancer, variants with enhanced activity are associated with degenerative diseases such as Alzheimer’s disease. This review describes the tightly controlled mechanisms that ensure PKC activity is perfectly balanced and what happens when these controls are deregulated. PKC isozymes serve as a paradigm for the wisdom of Confucius: “to go beyond is as wrong as to fall short.”

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Section: Pkc Family and Regulationmentioning

confidence: 99%

Protein kinase C: perfectly balanced

Newton

2018

Critical Reviews in Biochemistry and Molecular Biology

238

216

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“…5,6,8,9) PKC is a family of serine/threonine kinases that regulate a multitude of cellular processes, including proliferation, differentiation, apoptosis, inflammation, and migration. 20,21) The PKC family comprises ten distinct isozymes that can be divided into three subfamilies such as conventional PKC isozymes (α, βI, βII, and γ), novel PKC isozymes (δ, ε, η, and θ), and atypical PKC isozymes (ζ and ι/λ), based on their structural properties and co-factor requirements for activation (see review by Igumenova).…”

Section: Involvement Of Protein Kinase C-depen-dent Activation Of Nadmentioning

confidence: 99%

Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties

Horinouchi

Higashi

Mazaki

et al. 2016

Biological & Pharmaceutical Bulletin

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Cigarette mainstream smoke is composed of gas and tar phases and contains >4000 chemical constituents, including nicotine and tar. The substances in the gas phase but not in the tar phase can pass through the airway epithelial barrier, enter the systemic circulation via the pulmonary circulation, and increase systemic oxidative damage, leading to the development of cigarette smoking-related diseases such as atherosclerosis. Recently, we identified some stable carbonyl compounds, including acrolein (ACR) and methyl vinyl ketone (MVK), as major cytotoxic factors in nicotine-and tar-free cigarette smoke extract (CSE) of the gas phase. CSE, ACR, and MVK induce protein kinase C (PKC)-dependent activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and subsequent generation of reactive oxygen species (ROS) via NOX, causing plasma membrane damage and cell apoptosis. CSE, ACR, and MVK also trigger carbonylation of PKC, which is an irreversible oxidative modification. Cell damage and PKC carbonylation in response to treatment with CSE, ACR, or MVK are abolished by thiol-containing antioxidants such as N-acetyl-L-cysteine and reduced glutathione. Thus pharmacological modulation of PKC and NOX activities and the trapping of ROS are potential strategies for the prevention of diseases related to cigarette smoking.

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“…Within these subgroups are 10 kinases that play distinct roles in the regulation of gene expression and cell proliferation. The activation of PKCs modifies them from a quiescent cytosolic form, to an active, membrane-associated form (64). Beyond their role as cytoplasmic signal transduction molecules, there is also evidence to suggest they can serve as nuclear kinases as well.…”

Section: Introduction Of Cell Signaling Pathwaysmentioning

confidence: 99%

Cell Signaling Pathways That Regulate Antigen Presentation

Brutkiewicz

2016

The Journal of Immunology

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Cell signaling pathways regulate much in the life of a cell: from shuttling cargo through intracellular compartments and onto the cell surface, how it should respond to stress, protecting itself from harm (environmental insults or infections), to ultimately, death by apoptosis. These signaling pathways are important for various aspects of the immune response as well. However, not much is known in terms of the participation of cell signaling pathways in Ag presentation--a necessary first step in the activation of innate and adaptive T cells. In this brief review, I will discuss the known signaling molecules (and pathways) that regulate how Ags are presented to T cells and the mechanism(s) if identified. Studies in this area have important implications in vaccine development and new treatment paradigms against infectious diseases, autoimmunity and cancer.

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Dynamics and Membrane Interactions of Protein Kinase C

Cited by 69 publications

References 143 publications

Protein kinase C: perfectly balanced

Protein kinase C: perfectly balanced

Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties

Cell Signaling Pathways That Regulate Antigen Presentation

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