Dissertations / Theses: 'Protein kinase c gamma'

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Das, Satyabrata. "Role of protein kinase C-gamma in the regulation of lens gap junctions." Diss., Manhattan, Kan. : Kansas State University, 2009. http://hdl.handle.net/2097/2330.

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Snider, Adam K. "PKC gamma regulates connexin 57." Thesis, Manhattan, Kan. : Kansas State University, 2010. http://hdl.handle.net/2097/4128.

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Abeliovich, Asa 1964. "The role of protein kinase C[gamma] in mammalian central nervous system function : a genetic approach." Thesis, Massachusetts Institute of Technology, 1994. http://hdl.handle.net/1721.1/33488.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1994.
On t.p., "[gamma]" appears as the lower case Greek letter.
Includes bibliographical references.
by Asa Abeliovich.
Ph.D.

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CAZAUBON, SYLVIE. "Etude structurale et fonctionnelle de la proteine kinase c-gamma : approche immunochimique." Paris 7, 1990. http://www.theses.fr/1990PA077184.

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Une approche immunochimique a ete envisagee pour caracteriser la proteine kinase c (pkc), mediateur intracellulaire dont l'activite est regulee par le second messager diacylglycerol ou par les promoteurs de tumeurs de la classe des esters de phorbol. Nous avons produit et caracterise quatre anticorps monoclonaux diriges contre l'isotype gamma de la pkc: 3g12, 5a2, 15g4 et 36g9. Ces quatre anticorps monoclonaux reconnaissent specifiquement le domaine de regulation de la pkc-gamma provenant de differents mammiferes et deux d'entre eux (5a2 et 36g9) inhibent l'activite catalytique de l'enzyme dependante des effecteurs: ester de phorbol, phospholipides et calcium. Reciproquement, la liaison de 5a2 et de 36g9 est bloquee respectivement en presence des phospholipides et des phospholipides plus ester de phorbol. A l'aide de molecules de pkc-gamma deletees, nous avons determine que les residus essentiels a la structure des epitopes sont distincts des sites de liaison des effecteurs. Ces resultats suggerent que la liaison des phospholipides et de l'ester de phorbol induit des changements de conformation qui sont responsables de la perte de l'immunoreactivite de l'enzyme. Nous proposons donc que l'activation de la pkc par ses effecteurs est le resultat de modifications conformationnelles qui permettent a l'enzyme de lier le substrat exogene

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Yevseyenkov, Vladimir. "PKC gamma senses/protects from stress in retina through regulation of gap junctions." Diss., Kansas State University, 2010. http://hdl.handle.net/2097/6306.

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Doctor of Philosophy
Department of Biochemistry
Dolores J. Takemoto
Exposure to oxidative stress leads to accumulation of reactive oxygen species and this stimulates protective cellular functions as a compensatory response to prevent the spread of apoptotic signal and prevent cell death. The purpose of this dissertation is to understand the importance of PKCγ activation and regulation of the retinal gap junction protein Cx50, and what role PKCγ plays in this neuro-protective effect. Through electron microscopy we were able to show that PKCγ knockout mice retinas had incomplete cellular organization in the outer plexiform layer (OPL) of the retina, the layer of retina where Cx50 plays an important role in retinal cellular synapses. Electroretinograms confirmed that this structural disorganization also led to loss of functional response to light stimuli in PKCγ knockout mice retinas. In vivo exposure to 100% hyperbaric oxygen (HBO) caused significant degradation of the retina in knockout mice compared to control mice. Thicknesses of the inner and nuclear and ganglion cell layers were increased, with complete disruption of OPL in PKCγ KO mice retinas. Damage to the outer segments of the photoreceptor layer and ganglion cell layer was significantly more apparent in the central retinas of HBO-treated knockout mice. Cx50 immunolabeling showed significant reduction to HBO treatment of PKCγ control mice retinas, HBO treatment failed to produce reduction of Cx50 immunolabeling in KO mice retinas. In the R28 retinal cell line, PKCγ enzyme was shown to be activated by phorbol ester (TPA) and hydrogen peroxide. This resulted in translocation to the cellular membrane as confirmed by western blot and confocal microscopy. Suppression of PKCγ by siRNA rendered R28 cells more sensitive to oxidative stress-induced cell apoptosis, the process of apoptosis started earlier, and this resulted in cell death. R28 treatment with phorbol esters and hydrogen peroxide led to reduction in gap junction activity and Cx50 gap junction cell disassembly. This dissertation shows that PKCγ plays an important role in structural organization of retina and has a neuro-protective effect in response to oxidative stress, in part because of its control of Cx50.

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Viard, Patricia. "Régulation des canaux calciques vasculaires de type L par les sous-unités Beta-Gamma de protéines G." Bordeaux 2, 1999. http://www.theses.fr/1999BOR28696.

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Thérier, Julien. "Régulation de la voie des Mitogen-Activated Protein Kinase ERK1/2 par la phospholipase C gamma dans le signal du Macrophage-Colony Stimulating Factor." Lyon 1, 2005. http://www.theses.fr/2005LYO10121.

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Le M-CSF régule l'établissement du lignage monocytaire/macrophagique en assurant la survie, la prolifération mais aussi la différenciation des progéniteurs myéloïdes en cellules très spécialisées : les macrophages. Ce contrôle nécessite la transduction d'un signal intracellulaire impliquant de nombreuses molécules. Parmi celles-ci, les MAPK ERK1/2 présentent une cinétique d'activation caractéristique : une première vague de phosphorylation rapide et transitoire puis une seconde vague tardive et soutenue essentielle à la différenciation macrophagique. J'ai montré au cours de cette étude que la phospholipase C régule spécifiquement cette seconde vague d'activation des kinases ERK1/2 par l'intermédiaire de Ras. Ce processus, indépendant du diacylglycérol, fait intervenir de façon prépondérante l'augmentation du taux de calcium intracellulaire. Ces résultats constituent un mécanisme d'activation original faisant potentiellement intervenir les kinases Src ou les complexes Gab2/SHP2

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Zamani, Marzieh. "The role of the JNK/AP-1 pathway in the induction of iNOS and CATs in vascular cells." Thesis, University of Hertfordshire, 2013. http://hdl.handle.net/2299/10626.

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Nitric oxide (NO) is an important biological molecule within the body, which over production of this molecule in response to different stimulations can cause various inflammatory diseases. Over production of this molecule is caused by the induction of the inducible nitric oxide synthase (iNOS) enzyme. This enzyme uses L-arginine as a substrate and therefore the presence and transport of this amino acid into the cells can be a key factor in regulating NO over production. Different signalling mechanisms have been implicated in the regulation of this pathway and one of which involves the Mitogen Activated Protein Kinases (MAPK). This family of proteins respond to inflammatory conditions and may mediate effects induced by inflammatory mediators. Of the MAPKs, the role of the c-Jun-N-terminal kinase (JNK) pathway in the induction of iNOS is still controversial. JNK and its downstream target, the transcription factor Activator Protein-1 (AP-1), have shown contradictory effects on iNOS induction leading to controversies over their role in regulating iNOS expression in different cell systems or with various stimuli. The studies described in this thesis have determined the role of JNK/AP-1 on iNOS expression, NO production, L-arginine uptake and also on the transporters responsible for L-arginine transport into the cells. The studies were carried out in two different cell types: rat aortic smooth muscle cells (RASMCs) and J774 macrophages which are both critically associated with the over production of NO in vascular inflammatory disease states. The first approach was to block the expression of the inducible L-arginine-NO pathway using SP600125 and JNK Inhibitor VIII which are both pharmacological inhibitors of JNK. The results from these studies showed that the pharmacological intervention was without effect in RASMCs, but inhibited iNOS, NO and L-arginine transport in J774 macrophages. In contrast, the molecular approach employed using two dominant negative constructs of AP-1 (TAM-67 and a-Fos) revealed a different profile of effects in RASMCs, where a-Fos caused an induction in iNOS and NO while TAM-67 had an inhibitory effect on iNOS, NO, L-arginine transport and CAT-2B mRNA expression. The latter was unaffected in RASMCs but suppressed in J774 macrophages by SP600125. Examination of JNK isoforms expression showed the presence of JNK1 and 2 in both cell systems. Moreover, stimulation with LPS/IFN- or LPS alone resulted in JNK phosphorylation which did not reveal any difference between smooth muscle cells and macrophages. In contrast, expression and activation of AP-1 subunits revealed differences between the two cell systems. Activation of cells with LPS and IFN- (RASMCs) or LPS alone (J774 macrophages) resulted in changes in the activated status of the different AP-1 subunit which was different for the two cell systems. In both cell types c-Jun, JunD and Fra-1 were increased and in macrophages, FosB activity was also enhanced. Inhibition of JNK with SP600125 caused down-regulation in c-Jun in both cell types. Interestingly this down-regulation was in parallel with increases in the subunits JunB, JunD, c-Fos and Fra-1 in RASMCs or JunB and Fra-1 in J774 macrophages. Since, SP600125 was able to exert inhibitory effects in the latter cell type but not in RASMCs, it is possible that the compensatory up-regulation of certain AP-1 subunits in the smooth muscle cells may compensate for c-Jun inhibition thereby preventing suppression of iNOS expression. This notion clearly needs to be confirmed but it is potentially likely that hetero-dimers formed between JunB, JunD, c-Fos and Fra-1 could sustain gene transcription in the absence of c-Jun. The precise dimer required has not been addressed but unlikely to exclusively involve JunB and Fra-1 as these are up-regulated in macrophages but did not sustain iNOS, NO or induced L-arginine transport in the presence of SP600125. To further support the argument above, the dominant negatives caused varied effects on the activation of the different subunits. a-Fos down-regulated c-Jun, c-Fos, FosB, Fra-1 whereas TAM-67 reduced c-Jun and c-Fos but marginally induced Fra-1 activity. Associated with these changes was an up-regulation of iNOS-NO by a-Fos and inhibition by TAM-67. Taken together, the data proposes a complex mechanism(s) that regulate the expression of the inducible L-arginine-NO pathway in different cell systems and the complexity may reflect diverse intracellular changes that may be different in each cell type and not always be apparent using one experimental approach especially where this is pharmacological. Moreover, these findings strongly suggest exercising caution when interpreting pure pharmacological findings in cell-based systems particularly where these are inconsistent or contradictory.

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9

Robinson, Karen Ann. "Protein regulators of kinase C." Thesis, University College London (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282756.

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10

Oliva, Rossella Norma. "Characterization of the isoform gamma 2 ([gamma] 2) of the serinethreonine protein kinase Casein Kinase I (CKI-[gamma] 2)." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81369.

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Casein Kinase I (CKI) is one of the first serine/threonine protein kinase activities to be isolated and characterized. In vertebrates, CKI represent a multigene family with seven isoforms, alpha, beta, delta, ε, gamma1-3 for which, very little is known with respect to their biological functions. This study reports that stable overexpression of CKI-gamma2 into fibroblasts impairs cell morphology and the organization of the actin cytoskeleton in a kinase-dependent mechanism and cell proliferation through a kinase-independent mechanism. In addition, by immunofluorescence we determined the subcellular distribution of CKI-gamma2 to perinuclear vesicles. Furthermore, we established that a putative prenylation motif present in the C-terminal extension of CKI-gamma2 determines its proper subcellular localization.

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11

Chen, Dan. "Regulation of protein kinase C by protein-protein interactions /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3112821.

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12

Stafford, Margaret Jackson. "Protein kinase C in platelet signalling." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275204.

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13

Murphy, John Anthony. "The protein kinase C of glia." Thesis, University of York, 1989. http://etheses.whiterose.ac.uk/9762/.

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14

Edwards, Amelia S. "Interdomain regulation of protein kinase C /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9901441.

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15

Hocevar, Barbara Ann. "Characterization of nuclear protein kinase C." Case Western Reserve University School of Graduate Studies / OhioLINK, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=case1057177248.

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16

Kumar, Varun. "Protein Kinase C Signaling in Neurodegeneration." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051.

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17

Kirwan, Angie F. "Inhibitory properties of the regulatory domains of human protein kinase C Ã and protein kinase C [epsillon]." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0005/MQ31443.pdf.

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Wang, Jingwei. "Alterations in protein kinase A and protein kinase C activities and protein levels in cardiomyopathy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0001/MQ32280.pdf.

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19

Dutil, Erica M. "Phosphorylation of protein kinase C by the phosphoinositide-dependent kinase /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9961757.

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20

Marach, Jaime A. "Processing of protein kinase C by phosphorylation /." Diss., Connect to a 24 p. preview or request complete full text in PDF formate. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3236626.

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21

Durgan, Joanne. "Protein Kinase C-binding partners & phosphorylation." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444645/.

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Protein Kinase C (PKC) comprises a family of phospholipid-dependent Ser/Thr kinases, implicated in a broad array of cellular processes. PKC activity is subject to a complex network of regulatory inputs, including co-factor binding, phosphorylation and protein-protein interaction. In addition, the chronic activation of PKC frequently leads to its down-regulation this process may be intrinsic to the tumour promoting activity of the phorbol esters. The aim of this work was to investigate the regulation of the novel PKC-e isoform by binding partners and phosphorylation, with a particular focus on the process of agonist-induced degradation. A yeast 2-hybrid screen was performed using a PKC-e bait and two novel binding partners were identified, both with associations to the ubiquitin/proteasome system VHL Binding Protein 1 (VBP1) and F-box WD40 protein 7 (Fbw7). Interactions were verified in mammalian cells and mapped to the catalytic domain of PKC-e. Extensive studies revealed that neither partner influenced the process of PKC-e down-regulation. However, Fbw7a was demonstrated to represent an in vitro PKC substrate. The site of phosphorylation was mapped to Ser-18 and, using phospho-specific antibodies, was shown to be phosphorylated in the cell. PKC-e activity is required for its agonist-induced degradation. Studies were therefore undertaken to investigate autophosphorylation, which may be implicated in this process. Serine residues 234, 316 and 368 were identified as novel PKC-e autophosphorylation sites. Using phospho- specific antibodies, all three sites were shown to be occupied in response to PKC-e activation. Phosphorylation at these sites was found not to influence agonist-induced PKC-e down-regulation. However, a critical role was established for phosphorylated Ser-368, in the recruitment of the PKC-e binding partner, 14-3-3(3. Together these findings provide insight into the mechanisms controlling PKC-e activity and demonstrate a relationship between regulation through phosphorylation and protein-protein interaction.

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22

Srivastava, Jyoti. "Regulation of protein kinase C delta degradation." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252381.

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Violin, Jonathan D. "Spatiotemporal dynamics of Protein Kinase C signaling /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3094617.

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Marais, Richard Malcol. "Comparative studies on protein kinase C isotypes." Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47556.

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Rainey, Paul. "Studies into the antiapoptotic signalling of protein kinase B#gamma#." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342643.

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Hamza, Muhammad Sabry. "Transcription profile and protein kinase of lymphotropic gamma-2 herpesviruses /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2004. http://uclibs.org/PID/11984.

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Hermelink, Antje. "Phosphatidylinositol 3-kinase [gamma] characterization of a protein-lipid interaction." Berlin dissertation.de, 2008. http://d-nb.info/994112912/04.

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Ratnayake, Wishrawana Sarathi Bandara. "Role of Oncogenic Protein Kinase C-iota in Melanoma Progression; A Study Based on Atypical Protein Kinase-C Inhibitors." Scholar Commons, 2019. https://scholarcommons.usf.edu/etd/7895.

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Irrespective of plentiful efforts to enhance primary prevention and early detection, the number of melanoma cases in the United States has increased steadily over the past 30 years, thus greatly affecting public health and the economy. We have investigated the effects of five novel aPKC inhibitors; 2-acetyl-1,3-cyclopentanedione (ACPD), 3,4-Diaminonaphthalene-2,7-disulfonic acid (DNDA), [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1T) along with its nucleoside analog 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S) and 8-hydroxy-1,3,6-naphthalenetrisulfonic acid (ζ-Stat) on cell proliferation, apoptosis, migration and invasion of two malignant melanoma cell lines compared to normal melanocyte cell lines. Molecular docking data suggested that both ACPD and DNDA specifically bind to protein kinase C-zeta (PKC-ζ) and PKC-iota (PKC-ι) while both ICA-1 compounds specifically bind to PKC-ι, and ζ-Stat showed a high affinity towards PKC-ζ. Kinase activity assays were carried out to confirm these observations. Results suggest that PKC-ι is involved in melanoma malignancy than PKC-ζ. Both isoforms promote the activation of nuclear factor (NF)-κB and protein kinase B (AKT) thereby supporting survival and progression. In addition, we demonstrated that PKC-ι induced the metastasis of melanoma cells by activating Vimentin, and PKC-ι inhibition downregulated epithilial-mesencymal transition (EMT), while inducing apoptosis. Of note, PKC-ἱ specific inhibitors downregulated the expression of both PKC-ι and phosphorylated PKC-ι, suggesting that PKC-ι plays a role in regulating its own expression in melanoma. We also report the underlaying mechanisms of the transcriptional regulation of PKC-ι (PRKCI gene) expression in melanoma. c-Jun, interferon-stimulated gene factor 3 (ISGF3), paired box gene 3 (PAX3), early growth response protein 1 (EGR1) and forkhead box protein O1 (FOXO1), which bind on or near the promoter sequence of the PRKCI gene, were analyzed for their role in PKC-ι regulation in SK-MEL-2 and MeWo cell lines. We silenced selected transcription factors using siRNA, and the results revealed that the silencing of c-Jun and FOXO1 significantly altered the expression of PRKCI. The levels of both phosphorylated and total PKC-ι increased upon FOXO1 silencing and decreased upon c-Jun silencing, suggesting that c-Jun acts as an upregulator, while FOXO1 acts as a downregulator of PRKCI expression. We also used a multiplex ELISA to analyze multiple pathways other than NF-κB that were affected by treatment with PKC-ι inhibitor. The silencing of NF-κB p65 and PKC-ι by siRNA suggested that the regulation of PKC-ι expression was strongly associated with FOXO1. In addition, we observed a significant decrease in the mRNA levels of both interleukin (IL)-6 and IL-8, with a significant increase in the levels of IL-17E and intercellular adhesion molecule 1 (ICAM-1) upon the knockdown of expression of PKC-ι in both cell lines. This suggested that PKC-ι expression was affected by these cytokines in an autocrine manner. Overall, the findings of this study suggest that PKC-ι inhibition suppresses its own expression, diminishing oncogenic signaling, while upregulating anti-tumor signaling, thus rendering it an effective novel biomarker for use in the design of novel targeted therapeutics for melanoma.

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Hynes, Andrews Mark. "Rx-kinase and protein kinase C in superoxide production from neutrophils." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267858.

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30

Cheng, Kwan-wai. "Regulation of equilibrative nucleoside transporter-1 by protein kinase C and mitogen-activating protein kinase /." View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31494912.

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Desai, Shraddha R. "Role of Protein Kinase C-iota in Glioblastoma." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3070.

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The focus of this research was to investigate the role of protein kinase C-iota (PKC-é) in the regulation of Bad function, a pro-apoptotic member of the Bcl-2 family and Cdk7 function, a master cell cycle regulator in glioblastoma. The results were obtained from the human glial tumor derived cell lines, T98G and U87MG. In these cells, PKC-é co-localized and directly associated with Bad as shown by immunofluorescence, immunoprecipitation, and Western blotting. Furthermore, in-vitro kinase activity assay showed that PKC-é directly phosphorylated Bad at phospho specific residues, S112, S136 and S155 which in turn induced inactivation of Bad and disruption of the Bad/Bcl-XL dimer. Knockdown of PKC-é by siRNA exhibited a corresponding reduction in Bad phosphorylation suggesting that PKC-é may be a Bad kinase. Since, PKC-é is an essential downstream mediator of the PI (3)-kinase, we hypothesize that glioma cell survival is mediated via a PI (3)-kinase/PDK1/PKC-é/Bad pathway. Treatment with PI(3)-kinase inhibitors Wortmannin and LY294002, as well as PDK1 siRNA, inhibited PKC-é activity and subsequent phosphorylation of Bad suggesting that PKC-é regulates the activity of Bad in a PI (3)-kinase dependent manner. Robust expression of PKC-é is a hallmark of human glioma and benign and malignant meningiomas, however, little is understood about its role in glioma cell proliferation. The cyclin dependent kinase activating kinase complex (CAK), comprises of cyclin dependent kinase 7 (Cdk7), cyclin H and MAT1, is the master cell regulator. Cdk7 phosphorylates its downstream cyclin dependent kinases (cdks) and promotes cell proliferation. Results show that PKC-é directly associated and phosphorylated Cdk7 at T170. Furthermore, Cdk7 phosphorylated its downstream target, cyclin dependent kinase 2 (cdk2) at T160. Purified PKC-é was also observed to phosphorylate endogenous as well as exogenous Cdk7. PKC-é knockdown with siRNA, PDK1 siRNA and (PI) 3-kinase inhibitors, Wortmannin and LY294002 treatment exhibited corresponding reduction in phosphorylation of Cdk7 and subsequently cdk2. In addition, PKC-é knockdown reduced cell proliferation; led to cell cycle arrest and also induced apoptosis. Thus, these findings suggest the presence of a novel PI (3)-kinase/PKC-é/BAD mediated cell survival and PI (3)-kinase/PKC-é/Cdk7 mediated cell proliferation pathway.

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Gordge, Philip Charles. "Potential agonists and inhibitors of protein kinase C." Thesis, University College London (University of London), 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285430.

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Hong, Ying. "Regulation of megakaryocytic differentiation by protein kinase C." Thesis, King's College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286361.

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Mills, Julia. "Regulation of amyloid precursor protein catabolism in vitro, the role of mitogen-activated protein kinase and protein kinase C." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/nq27201.pdf.

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Almami, I. "Modulation of transglutaminase 2 activity in H9c2 cells by protein kinase A and protein kinase C signalling." Thesis, Nottingham Trent University, 2014. http://irep.ntu.ac.uk/id/eprint/34659/.

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Transglutaminase 2 (TG2; EC 2.3.2.13) has been shown to protect cardiomyocytes against ischaemia and reperfusion-induced cell death and to mediate cell survival in many cell types. Given the prominent role of PKA and PKC in cardioprotection, this study investigated whether TG2 was involved in the cytoprotection induced by activation of these two kinases in cardiomyocyte-like H9c2 cells. Cultured H9c2 cells were extracted following stimulation with activators of PKC (phorbol-12-myristate-13-acetate; PMA) and PKA (forskolin; FK). Transglutaminase 2 activity was determined using an amine incorporating (in vitro and in situ) and a protein crosslinking assays. Different protein kinase inhibitors were used to determine the involvement of PKC and PKA in the activation of TG2 in H9c2 cells. To confirm the involvement of TG2 activity via PKC and PKA, TG2 specific (Z-DON and R283) inhibitors were used. Western blot analysis revealed the presence of TG2 and TG1 (TG2 >> TG1) protein, but not TG3. Since the H2O2, a major contributor to reactive oxygen species following damage was used to induce oxidative stress. The role of TG2 in PMA- and forskolin-induced cytoprotection was investigated by monitoring H2O2-induced oxidative stress in H9c2 cells. The identification of TG2 substrates in H9c2 cells was investigated using pull down assay coupled with proteomic analysis techniques. The PMA and FK-induced time and concentration-dependent increases in TG2 catalysed biotin cadaverine incorporation in H9c2 cells. Forskolin but not PMA also increased TG2 catalysed protein crosslinking. The PKC (Ro-31 8220) and PKA (KT 5720 and Rp-8-Cl-cAMPS) inhibitors, blocked PMA and FK-induced TG2 activity. Immunocytochemistry using ExtrAvidin®-FITC revealed in situ TG2-mediated biotin cadaverine incorporation into protein substrates following stimulation of PMA, FK and their receptor agonists. The TG2 inhibitors Z-DON and R283 attenuated the PMA- and FK-induced increases in TG2 activity. Pre-treatment with PMA and FK reversed H2O2-induced cell death as judged by a MTT reduction assay and the release of cellular LDH. The TG2 inhibitors R283 and Z-DON blocked PMA and FK-induced cytoprotection. Proteomic analysis identified more than 25 proteins that serve as intracellular substrates for TG2 following PMA and FK stimulation. Some of these identified proteins have already been reported as TG2 substrates, but not in H9c2 cells e.g. tubulin while others e.g. α-actinin have not been identified before. In summary, these data have shown TG2 activity to be stimulated via PKA and PKC-dependent signalling pathways in H9c2 cells and suggest a role for TG2 in cytoprotection-induced via these two protein kinases.

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Thibault, Ginette. "Characterization of the phosphorylation of protein kinase C by phosphoinositide-dependent kinase 1." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79145.

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Phosphorylation of protein kinase Cs (PKCs) by phosphoinositide-dependent kinase I (PDK) is critical for PKC activity. In the nervous system of the marine mollusk Aplysia, there are only two major PKC isoforms, the calcium-activated PKC Apl I and the calcium-independent PKC Apl II, and both PKCs are persistently activated during intermediate memory. We monitored the PDK-dependent phosphorylation of PKC Apl I and PKC Apl II using phosphopeptide antibodies. PDK phosphorylation of PKCs was not sensitive to inhibitors of PI-3 kinase, PKC, nor to expression of a kinase-inactive PDK. Phosphorylation of a kinase inactive PKC was reduced, likely due to dephosphorylation. Localization of PDK-phosphorylated PKC Apl II using immunocytochemistry revealed an enrichment of phosphorylated PKC Apl II at the plasma membrane. These data suggest that increased PDK phosphorylation of PKC Apl II is important for persistent kinase activation. PKC phosphorylation at the PDK site is not affected by the presence of a kinase-inactive form of PDK. Using GFP (green fluorescent protein)-tagged PKC, which was microinjected into neurons, we determined that PKC was translocated to the juxta-membrane region by the PKC activator 4beta-phorbol ester 12,13-dibutyrate (PDBu).

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Roberts, Richard Edwards. "Protein kinase C, protein phosporylation, and nerve regeneration in experimental diabetic neuropathy." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295836.

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Baltuch, Gordon Hirsh. "Protein kinase C and growth regulation in malignant gliomas." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28984.

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Malignant gliomas represent over 50% of the tumours which originate within the central nervous system. Current treatment modalities are in large part unsuccessful, and less than 10% of patients with high grade glioblastomas survive beyond 2 years. Understanding the cause of the rapid growth rate of malignant gliomas would be useful in devising new therapeutic strategies to treat this disorder. Previous work from this laboratory suggested that the enzyme protein kinase C (PKC) was a critical regulator of the hyperproliferative state of glioma cells. The results presented in this thesis demonstrate that (1) PKC activity was differentially increased in glioma cell lines when compared to other fast growing cell types of non-glial origin, (2) inhibitors of PKC (staurosporine, tamoxifen, CGP 41 251) block the proliferation rate of glioma cells at IC50 values that correspond to their respective IC50's for inhibition of PKC activity, (3) of the PKC isoforms, rat astrocytes and rat glioma cells contain $ alpha, beta, delta, varepsilon$ and $ zeta$, but not $ gamma$, (4) of the expressed isoforms, the activity and amounts of PKC$ alpha$ correlate with cellular growth and (5) an anti-sense oligonucleotide directed against PKC$ alpha$ decreases the proliferation rate of glioma cells. These observations suggest that aberrations in PKC signal transduction (particularly PKC$ alpha$) are important factors in the growth of glioma and have led to clinical trials utilizing PKC inhibitors as adjuncts in the therapy of patients harbouring these incurable neoplams.

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Tian, Ya-Min. "The involvement of protein kinase C in insulin secretion." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337551.

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Toker, I. Alex. "Purification and characterisation of protein kinase C inhibitor proteins." Thesis, University College London (University of London), 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277909.

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Win, Hla Yee. "Role of protein kinase C-iota in prostate cancer." [Tampa, Fla.] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002322.

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Haughian, James M. "Defining protein kinase C function in endometrial cancer cells /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008. http://proquest.umi.com/pqdweb?did=1545964851&sid=2&Fmt=6&clientId=18952&RQT=309&VName=PQD.

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Thesis (Ph.D. in Reproductive Sciences) -- University of Colorado Denver, 2008.
Typescript. Includes bibliographical references (leaves 150-183). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

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43

Unsworth, Amanda J. "The role of protein kinase C in platelet activation." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:114582b8-185a-41f5-958c-77038fb185df.

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The Protein kinase C (PKC) superfamily is a key regulator in platelet activation with individual isoforms playing distinct roles. This thesis focuses on the role of the novel PKC isoforms downstream of several agonists using both pharmacological and genetic approaches and human and mouse platelets. Quantification of the protein levels of PKC isoforms identified different levels of the five major PKC isoforms expressed in human platelets and also differences between levels of the same isoform in human and mouse platelets. Use of a selection of broad spectrum and isoform-specific inhibitors, identified both positive and negative novel roles for PKC in the regulation of human and mouse platelets. A net positive role for PKC was found in GPVI, Clec-2, and PAR receptor signalling, with classical isoforms of PKC playing a major role in aggregation and dense granule secretion. A novel negative regulatory role was also identified in the regulation of ADP-induced platelet activation for PKC~, and both PKCE and PKC~ in human and mouse platelets respectively. Gene knock-out mouse models confirmed a positive regulatory role for PKCe in allb~3 outside-in signalling but identified no other regulatory role for PKCe in agonist induced platelet activation. Despite this relatively minor role, functional redundancy was identified between PKCe and PKCE isoforms in haemostasis, as tail bleeding was significantly increased in mice deficient in both novel isoforms. The work presented here identifies key roles for the PKC superfamily in the complex regulation of platelet activation, with different isoforms supporting and limiting the process of thrombus formation and haemostasis.

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Kang, Chen. "ION CHANNELS, PROTEIN KINASE C AND CAVEOLAE IN CARDIOPROTECTION." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1449158171.

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45

Bullenkamp, Jessica Isabell. "Tumour-specific regulation of apoptin by protein kinase C." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/tumourspecific-regulation-of-apoptin-by-protein-kinase-c(2e7dd4a3-e361-4ad1-8cf3-92d36f43b58e).html.

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Apoptin, the VP3 protein derived from chicken anaemia virus (CAV), induces tumour cell-specific apoptosis and therefore represents a potential anti-cancer therapeutic agent of the future. In human tumour cells, but not in normal cells, Apoptin is phosphorylated and subsequently translocates to the nucleus, which are essential important steps for its cytotoxic activity. Recently, the β isozyme of protein kinase C (PKCβ) was identified as a kinase phosphorylating Apoptin in multiple myeloma cells. However, the exact mechanism and nature of interaction between PKCβ and Apoptin as well as its importance for Apoptin-induced cell death remain to be characterised. This project aimed to further investigate the physical and functional interaction between PKC isoforms, in particular PKCβ, and Apoptin. Recently, the first human Gyrovirus (HGyV) was isolated which shows significant structural and organisational resemblance to CAV and encodes a homologue of CAV-Apoptin. Using a synthetic HGyV-Apoptin construct the subcellular distribution and apoptotic function of this novel Apoptin protein in several human cancer cell lines was analysed and compared to CAV-Apoptin. The results demonstrated a comparable tumour-specific nuclear translocation and cytotoxic effect between the two proteins. A model of colon carcinoma and normal mucosa cell lines was used to investigate the functional link between PKC and Apoptin in other cancer types. Immunoprecipitation and proximity ligation assay studies confirmed the binding of both CAV- and HGyV-Apoptin to PKCβI in HCT116 colorectal cancer cells and identified the N-terminal region of Apoptin to be important for the interaction with PKC. In contrast to HCT116 cells two normal colon mucosa cell lines tested expressed low levels of PKCβI. This differential expression pattern of PKCβI correlated with reduced Apoptin activation in normal cells, as evident by its localisation to the cytoplasm, decreased phosphorylation and lack of cytotoxic activity. Further studies revealed that PKCβI knockdown in HCT116 cells resulted in reduced Apoptin phosphorylation but did not impair Apoptin cytotoxicity. Additionally, overexpression of PKCβI was not sufficient to activate Apoptin in normal cell lines, indicating that other kinases or processes may contribute to the tumour-specific function of Apoptin. Using the FRET-based PKC activity reporter CKAR and fluorescence lifetime imaging microscopy (FLIM) the effect of Apoptin or other stimuli on PKC activity was analysed. Similar to treatment with the phorbol ester TPA, Apoptin expression in HCT116 cancer cells resulted in a significant increase in PKC activity, correlating with the expression and increased phosphorylation levels of Apoptin. In contrast, normal colon mucosa cell lines with low PKCβI expression showed a delayed and reduced induction of PKC activation in response to Apoptin. Overexpression and knockdown studies in combination with FLIM provided some evidence that Apoptin predominantly activates the PKCβI isoform in HCT116 cells. Another tumour-selective cytotoxic agent, TRAIL, was tested on a panel of head and neck cancer cell lines associated with human papillomavirus (HPV) infection. Addition of the proteasome inhibitor Bortezomib sensitised TRAIL-resistant HPV positive head and neck cancer cells to TRAIL. This seemed to involve activation of caspases, the anti-apoptotic protein XIAP as well as stabilisation of functional p53, but the precise mechanism has so far not yet been established. In conclusion, the results of this study propose an important link between Apoptin and PKCβI in cancer cells, involving their interaction and co-localisation, Apoptin-induced activation of PKC and PKCβI-mediated phosphorylation of Apoptin to promote its nuclear translocation and cytotoxic function. In addition, the novel HGyV-Apoptin was shown to function in a similar manner to CAV-Apoptin, providing a further tumourspecific protein for future studies.

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Karavana, Vassiliki. "Involvement of protein kinase C-epsilon in prostate malignancy." Thesis, University of Liverpool, 2008. http://livrepository.liverpool.ac.uk/3006348/.

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Young, Stephen W. "The insulin receptor tyrosine kinase and the activation of the map kinase cascade : interactions with the protein kinase C and protein kinase A signalling pathways." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238958.

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Fagerström, Sofia. "The expression and function of protein kinase C isoforms in differentiating neuroblastoma cells." Lund : Lund University, 1998. http://catalog.hathitrust.org/api/volumes/oclc/40342967.html.

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Cross, Timothy George. "Protein kinase C-#delta# is an apoptotic lamin kinase in myeloid leukaemic HL60 cells." Thesis, University of Birmingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368416.

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Dettori, Rosalia Angela [Verfasser], and Albrecht [Akademischer Betreuer] Piiper. "Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) / Rosalia Angela Dettori. Betreuer: Albrecht Piiper." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2011. http://d-nb.info/1051285267/34.

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Dissertations / Theses on the topic 'Protein kinase c gamma'

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