7,086 results match your criteria pkc isoforms


Ethanol inhibition of lateral orbitofrontal cortex neuron excitability is mediated via dopamine D1/D5 receptor-induced release of astrocytic glycine.

Neuropharmacology 2021 May 6:108600. Epub 2021 May 6.

Department of Neuroscience, Addiction Sciences Division Medical University of South Carolina Charleston, SC 29425; Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division Medical University of South Carolina Charleston, SC 29425. Electronic address:

Recent findings from this laboratory demonstrate that ethanol reduces the intrinsic excitability of orbitofrontal cortex (OFC) neurons via activation of strychnine-sensitive glycine receptors. Although the mechanism linking ethanol to the release of glycine is currently unknown, astrocytes are a source of neurotransmitters including glycine and activation of dopamine D1-like receptors has been reported to enhance extracellular levels of glycine via a functional reversal of the astrocytic glycine transporter GlyT1. We recently reported that like ethanol, dopamine or a D1/D5 receptor agonist increases a tonic current in lateral OFC (lOFC) neurons. Read More

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Oxidative stress induced by NOX2 contributes to neuropathic pain via plasma membrane translocation of PKCε in rat dorsal root ganglion neurons.

J Neuroinflammation 2021 May 6;18(1):106. Epub 2021 May 6.

Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Background: Nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-induced oxidative stress, including the production of reactive oxygen species (ROS) and hydrogen peroxide, plays a pivotal role in neuropathic pain. Although the activation and plasma membrane translocation of protein kinase C (PKC) isoforms in dorsal root ganglion (DRG) neurons have been implicated in multiple pain models, the interactions between NOX2-induced oxidative stress and PKC remain unknown.

Methods: A spared nerve injury (SNI) model was established in adult male rats. Read More

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Classical isoforms of protein kinase C (PKC) and Akt regulate the osteogenic differentiation of human dental follicle cells via both β-catenin and NF-κB.

Stem Cell Res Ther 2021 Apr 14;12(1):242. Epub 2021 Apr 14.

Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.

Background: Human dental follicle cells (DFCs) are the precursor cells of the periodontium with a high potential for regenerative therapies of (alveolar) bone. However, the molecular mechanisms of osteogenic differentiation are inadequately understood. Classical isoforms of protein kinase C (PKC) are reported to inhibit osteogenesis of stem/precursor cells. Read More

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Protein kinase C-mediated calcium signaling as the basis for cardiomyocyte plasticity.

Arch Biochem Biophys 2021 04 21;701:108817. Epub 2021 Feb 21.

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Moscow Region, Pushchino, Institutskaya, 3, 142290, Russia.

Protein kinase C is the superfamily of intracellular effector molecules which control crucial cellular functions. Here, we for the first time did the percentage estimation of all known PKC and PKC-related isozymes at the individual cadiomyocyte level. Broad spectrum of PKC transcripts is expressed in the left ventricular myocytes. Read More

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Nanoparticle-Encapsulated Bryostatin-1 Activates α-Secretase and PKC Isoforms In vitro and Facilitates Acquisition and Retention of Spatial Learning in an Alzheimer's Disease Mouse Model.

Curr Alzheimer Res 2020 ;17(14):1302-1310

LSU Health Sciences Center in Shreveport, Shreveport, Louisiana, LA, United States.

Background: Alzheimer's disease (AD) animal models have revealed neuroprotective actions of Bryostatin-1 mediated by activation of novel PKC isoforms, suppression of beta-amyloid and downregulation of inflammatory and angiogenic events, making Bryostatin-1 an attractive candidate for attenuating AD-associated neural, vascular, and cognitive disturbances.

Objective: To further enhance Bryostatin-1 efficacy, nanoparticle-encapsulated Bryostatin-1 formulations were prepared.

Methods: We compared nano-encapsulated and unmodified Bryostatin-1 in in vitro models of neuronal PKC-d, PKC-e isoforms, α-secretase and studied nano-encapsulated Bryostatin-1 in an AD mouse model of spatial memory (BC3-Tg (APPswe, PSEN1 dE9) 85Dbo/J mice). Read More

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January 2020

The Kinase Specificity of Protein Kinase Inhibitor Peptide.

Front Pharmacol 2021 29;12:632815. Epub 2021 Jan 29.

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, United States.

G-protein-coupled-receptor (GPCR) signaling is exquisitely controlled to achieve spatial and temporal specificity. The endogenous protein kinase inhibitor peptide (PKI) confines the spatial and temporal spread of the activity of protein kinase A (PKA), which integrates inputs from three major types of GPCRs. Despite its wide usage as a pharmaceutical inhibitor of PKA, it was unclear whether PKI only inhibits PKA activity. Read More

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January 2021

Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Front Pharmacol 2020 20;11:553852. Epub 2021 Jan 20.

Drug Research Program and Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

Hypertrophy of cardiomyocytes (CMs) is initially a compensatory mechanism to cardiac overload, but when prolonged, it leads to maladaptive myocardial remodeling, impairing cardiac function and causing heart failure. A key signaling molecule involved in cardiac hypertrophy is protein kinase C (PKC). However, the role of different PKC isoforms in mediating the hypertrophic response remains controversial. Read More

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January 2021

Atypical protein kinase C is essential for embryonic vascular development in mice.

Genesis 2021 Mar 6;59(3):e23412. Epub 2021 Feb 6.

Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China.

The atypical PKC (aPKC) subfamily constitutes PKCζ and PKCλ in mice, and both aPKC isoforms have been proposed to be involved in regulating various endothelial cell (EC) functions. However, the physiological function of aPKC in ECs during embryonic development has not been well understood. To address this question, we utilized Tie2-Cre to delete PKCλ alone (PKCλ-SKO) or both PKCλ and PKCζ (DKO) in ECs, and found that all DKO mice died at around the embryonic day 11. Read More

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Role of Protein Kinase C in Immune Cell Activation and Its Implication Chemical-Induced Immunotoxicity.

Adv Exp Med Biol 2021 ;1275:151-163

Department of Drug Sciences, Università di Pavia, Pavia, Italy.

Protein kinase C (PKCs) isoforms play a key regulatory role in a variety of cellular functions, including cell growth and differentiation, gene expression, hormone secretion, etc. Patterns of expression for each PKC isoform differ among tissues, and it is also clear that different PKCs are often not functionally redundant, for example specific PKCs mediate specific cellular signals required for activation, proliferation, differentiation and survival of immune cells. In the last 20 years, we have been studying the role of PKCs, mainly PKCβ and its anchoring protein RACK1 (Receptor for Activated C Kinase 1), in immune cell activation, and their implication in immunosenescence and immunotoxicity. Read More

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February 2021

Signal Transduction in Immune Cells and Protein Kinases.

Adv Exp Med Biol 2021 ;1275:133-149

Immunology Department, Victor Babes National Institute, Bucharest, Romania.

Immune response relies upon several intracellular signaling events. Among the protein kinases involved in these pathways, members of the protein kinase C (PKC) family are prominent molecules because they have the capacity to acutely and reversibly modulate effector protein functions, controlling both spatial distribution and dynamic properties of the signals. Different PKC isoforms are involved in distinct signaling pathways, with selective functions in a cell-specific manner. Read More

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February 2021

Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes.

Sci Rep 2021 Jan 8;11(1):207. Epub 2021 Jan 8.

School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, 4072, Australia.

The long-standing perception of Protein Kinase C (PKC) as a family of oncoproteins has increasingly been challenged by evidence that some PKC isoforms may act as tumor suppressors. To explore the hypothesis that activation, rather than inhibition, of these isoforms is critical for anticancer activity, we isolated and characterized a family of 16 novel phorboids closely-related to tigilanol tiglate (EBC-46), a PKC-activating epoxytigliane showing promising clinical safety and efficacy for intratumoral treatment of cancers. While alkyl branching features of the C12-ester influenced potency, the 6,7-epoxide structural motif and position was critical to PKC activation in vitro. Read More

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January 2021

Identification of Key Phospholipids That Bind and Activate Atypical PKCs.

Biomedicines 2021 Jan 6;9(1). Epub 2021 Jan 6.

Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.

PKCζ and PKCι/λ form the atypical protein kinase C subgroup, characterised by a lack of regulation by calcium and the neutral lipid diacylglycerol. To better understand the regulation of these kinases, we systematically explored their interactions with various purified phospholipids using the lipid overlay assays, followed by kinase activity assays to evaluate the lipid effects on their enzymatic activity. We observed that both PKCζ and PKCι interact with phosphatidic acid and phosphatidylserine. Read More

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January 2021

Evaluating the current status of protein kinase C (PKC)-protein kinase D (PKD) signalling axis as a novel therapeutic target in ovarian cancer.

Biochim Biophys Acta Rev Cancer 2021 01 28;1875(1):188496. Epub 2020 Dec 28.

Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Sector-125, Noida, Uttar Pradesh 201303, India. Electronic address:

Ovarian cancer, especially high grade serous ovarian cancer is one of the most lethal gynaecological malignancies with high relapse rate and patient death. Notwithstanding development of several targeted treatment and immunotherapeutic approaches, researchers fail to turn ovarian cancer into a manageable disease. Protein kinase C (PKC) and protein kinase D (PKD) are families of evolutionarily conserved serine/threonine kinases that can be activated by a plethora of extracellular stimuli such as hormones, growth factors and G-protein coupled receptor agonists. Read More

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January 2021

PKC downregulation upon rapamycin treatment attenuates mitochondrial disease.

Nat Metab 2020 12 14;2(12):1472-1481. Epub 2020 Dec 14.

Department of Genome Sciences, University of Washington, Seattle, WA, USA.

Leigh syndrome is a fatal neurometabolic disorder caused by defects in mitochondrial function. Mechanistic target of rapamycin (mTOR) inhibition with rapamycin attenuates disease progression in a mouse model of Leigh syndrome (Ndufs4 knock-out (KO) mouse); however, the mechanism of rescue is unknown. Here we identify protein kinase C (PKC) downregulation as a key event mediating the beneficial effects of rapamycin treatment of Ndufs4 KO mice. Read More

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December 2020

Alternative AKT2 splicing produces protein lacking the hydrophobic motif regulatory region.

PLoS One 2020 30;15(11):e0242819. Epub 2020 Nov 30.

Biomedizinisches Forschungslabor, Medizinische Klinik 1, Universitätsklinik Frankfurt, Frankfurt, Germany.

Three AKT serine/threonine kinase isoforms (AKT1/AKT2/AKT3) mediate proliferation, metabolism, differentiation and anti-apoptotic signals. AKT isoforms are activated downstream of PI3-kinase and also by PI3-kinase independent mechanisms. Mutations in the lipid phosphatase PTEN and PI3-kinase that increase PIP3 levels increase AKT signaling in a large proportion of human cancers. Read More

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January 2021

Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications.

Redox Biol 2020 10 13;37:101799. Epub 2020 Nov 13.

Department of Pathology, The University of Hong Kong, Hong Kong SAR, 999077, China. Electronic address:

Oxidative stress, a cytopathic outcome of excessive generation of ROS and the repression of antioxidant defense system for ROS elimination, is involved in the pathogenesis of multiple diseases, including diabetes and its complications. Retinopathy, a microvascular complication of diabetes, is the primary cause of acquired blindness in diabetic patients. Oxidative stress has been verified as one critical contributor to the pathogenesis of diabetic retinopathy. Read More

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October 2020

Distinct Regulation of Cardiac Fibroblast Proliferation and Transdifferentiation by Classical and Novel Protein Kinase C Isoforms: Possible Implications for New Antifibrotic Therapies.

Mol Pharmacol 2021 02 25;99(2):104-113. Epub 2020 Nov 25.

Drug Research Program and Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland

Cardiac fibrosis is characterized by accumulation and activation of fibroblasts and excessive production of extracellular matrix, which results in myocardial stiffening and eventually leads to heart failure. Although previous work suggests that protein kinase C (PKC) isoforms play a role in cardiac fibrosis and remodeling, the results are conflicting. Moreover, the potential of targeting PKC with pharmacological tools to inhibit pathologic fibrosis has not been fully evaluated. Read More

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February 2021

Function-Oriented Synthesis: Design, Synthesis, and Evaluation of Highly Simplified Bryostatin Analogues.

J Org Chem 2020 12 17;85(23):15116-15128. Epub 2020 Nov 17.

Department of Chemistry, Stanford University, Stanford, California 94305, United States.

Using a function-oriented synthesis strategy, we designed, synthesized, and evaluated the simplest bryostatin 1 analogues reported to date, in which bryostatin's A- and B-rings are replaced by a glutarate linker. These analogues, one without and one with a C26-methyl group, exhibit remarkably different protein kinase C (PKC) isoform affinities. The former exhibited bryostatin-like binding to several PKC isoforms with 's < 5 nM, while the latter exhibited PKC affinities that were up to ∼180-fold less potent. Read More

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December 2020

Equivocal, explicit and emergent actions of PKC isoforms in cancer.

Nat Rev Cancer 2021 01 11;21(1):51-63. Epub 2020 Nov 11.

Protein Phosphorylation Laboratory, Francis Crick Institute, London, UK.

The maturing mutational landscape of cancer genomes, the development and application of clinical interventions and evolving insights into tumour-associated functions reveal unexpected features of the protein kinase C (PKC) family of serine/threonine protein kinases. These advances include recent work showing gain or loss-of-function mutations relating to driver or bystander roles, how conformational constraints and plasticity impact this class of proteins and how emergent cancer-associated properties may offer opportunities for intervention. The profound impact of the tumour microenvironment, reflected in the efficacy of immune checkpoint interventions, further prompts to incorporate PKC family actions and interventions in this ecosystem, informed by insights into the control of stromal and immune cell functions. Read More

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January 2021

Protein Kinase C-Gamma Knockout Mice Show Impaired Hippocampal Short-Term Memory While Preserved Long-Term Memory.

Mol Neurobiol 2021 Feb 30;58(2):617-630. Epub 2020 Sep 30.

Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Pompeu Fabra University, 08003, Barcelona, Spain.

The brain encodes, stores, and retrieves relevant information in the form of memories that are classified as short-term (STM) and long-term memories (LTM) depending on the interval between acquisition and retrieval. It is classically accepted that STM undergo a consolidation process to form LTM, but the molecular determinants involved are not well understood. Among the molecular components relevant for memory formation, we focused our attention on the protein kinase C (PKC) family of enzymes since they control key aspects of the synaptic plasticity and memory. Read More

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February 2021

Actin reorganization at the centrosomal area and the immune synapse regulates polarized secretory traffic of multivesicular bodies in T lymphocytes.

J Extracell Vesicles 2020 Jun 19;9(1):1759926. Epub 2020 Jun 19.

Department of Metabolism and Cell Signaling, Instituto De Investigaciones Biomédicas Alberto Sols. CSIC-UAM, Madrid, Spain.

T-cell receptor stimulation induces the convergence of multivesicular bodies towards the microtubule-organizing centre (MTOC) and the polarization of the MTOC to the immune synapse (IS). These events lead to exosome secretion at the IS. We describe here that upon IS formation centrosomal area F-actin decreased concomitantly with MTOC polarization to the IS. Read More

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Protein and mRNA expression of protein kinase C (PKC) in the postmortem brain of bipolar and schizophrenic subjects.

J Psychiatr Res 2020 11 9;130:362-371. Epub 2020 Aug 9.

University of Illinois at Chicago, Department of Psychiatry, Chicago, IL, 60612, USA.

Abnormalities of protein kinase C (PKC) have been implicated in the pathophysiology of bipolar (BP) illness. This is primarily based on studies of PKC in platelets of BP patients. Whether such abnormalities of PKC activity and isoforms exist in the brain is unclear. Read More

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November 2020

The auxiliary subunit KCNE1 regulates KCNQ1 channel response to sustained calcium-dependent PKC activation.

PLoS One 2020 24;15(8):e0237591. Epub 2020 Aug 24.

Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States of America.

The slow cardiac delayed rectifier current (IKs) is formed by KCNQ1 and KCNE1 subunits and is one of the major repolarizing currents in the heart. Decrease of IKs currents either due to inherited mutations or pathological remodeling is associated with increased risk for cardiac arrhythmias and sudden death. Ca2+-dependent PKC isoforms (cPKC) are chronically activated in heart disease and diabetes. Read More

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October 2020

Involvement of protein kinase C beta1-serotonin transporter system dysfunction in emotional behaviors in stressed mice.

Neurochem Int 2020 11 18;140:104826. Epub 2020 Aug 18.

Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan; Department of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan. Electronic address:

Selective serotonin reuptake inhibitors are the first-line antidepressants for treating major depressive and post-traumatic stress disorders. These inhibitors directly bind to the serotonin transporter (SERT). Protein kinase C (PKC) is a key regulator of SERT functions as it can attenuate SERT activity through phosphorylation and its subsequent internalization. Read More

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November 2020

The role of PKC in CXCL8 and CXCL10 directed prostate, breast and leukemic cancer cell migration.

Eur J Pharmacol 2020 Nov 7;886:173453. Epub 2020 Aug 7.

School of Pharmacy, University of East Anglia, Norwich, NR4 7TJ, UK. Electronic address:

Migration of tumour cells is a fundamental process for the formation and progression of metastasis in malignant diseases. Chemokines binding to their cognate receptors induce the migration of cancer cells, however, the molecular signalling pathways involved in this process are not fully understood. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. Read More

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November 2020

Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models.

Mol Cell Biochem 2020 Oct 14;473(1-2):263-279. Epub 2020 Jul 14.

Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5246, ICBMS, 69622, Lyon, France.

Prostate cancer (PCa) is the most frequent cancer among men and the first cause of death over 65. Approximately 90% of patients with advanced disease will develop bone metastasis, which dramatically reduces long-term survival. Therefore, effective therapies need to be developed, especially when disease is still well-localized. Read More

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October 2020

Obligatory role for PKCδ in PIP -mediated activation of store-operated TRPC1 channels in vascular smooth muscle cells.

J Physiol 2020 09 21;598(18):3911-3925. Epub 2020 Jul 21.

Vascular Biology Research Centre, Molecular and Clinical Research Institute, St George's, University of London, Cranmer Terrace, London, UK.

Key Points: In vascular smooth muscle cells (VSMCs), activation of Ca -permeable store-operated channels (SOCs) composed of canonical transient receptor potential channel 1 (TRPC1) subunits mediates Ca entry pathways that regulate contraction, proliferation and migration, which are processes associated with vascular disease. Activation of TRPC1-based SOCs requires protein kinase C (PKC) activity, which is proposed to phosphorylate TRPC1 proteins to promote channel opening by phosphatidylinositol 4,5-bisphosphate (PIP ). We investigated the identity of the PKC isoform involved in activating TRPC1-based SOCs in rat mesenteric artery VSMCs. Read More

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September 2020

PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression.

Cancer Cell 2020 08 25;38(2):247-262.e11. Epub 2020 Jun 25.

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address:

Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during reactive oxygen species (ROS) generation, and how ROS promote tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) λ/ι loss in hepatocytes promotes autophagy and oxidative phosphorylation. Read More

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S92 phosphorylation induces structural changes in the N-terminus domain of human mitochondrial calcium uniporter.

Sci Rep 2020 06 4;10(1):9131. Epub 2020 Jun 4.

School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Buk-gu, Gwangju, 61005, Republic of Korea.

The mitochondrial calcium uniporter (MCU) plays essential roles in mitochondrial calcium homeostasis and regulates cellular functions, such as energy synthesis, cell growth, and development. Thus, MCU activity is tightly controlled by its regulators as well as post-translational modification, including phosphorylation by protein kinases such as proline-rich tyrosine kinase 2 (Pyk2) and AMP-activated protein kinase (AMPK). In our in vitro kinase assay, the MCU N-terminal domain (NTD) was phosphorylated by protein kinase C isoforms (PKC, PKC, and PKC) localized in the mitochondrial matrix. Read More

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Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.

Lipids Health Dis 2020 May 28;19(1):113. Epub 2020 May 28.

Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warszawa, Poland.

Protein kinase C (PKC) and Protein kinase D (PKD) isoforms can sense diacylglycerol (DAG) generated in the different cellular compartments in various physiological processes. DAG accumulates in multiple organs of the obese subjects, which leads to the disruption of metabolic homeostasis and the development of diabetes as well as associated diseases. Multiple studies proved that aberrant activation of PKCs and PKDs contributes to the development of metabolic diseases. Read More

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