Dissertations / Theses on the topic 'PKCe'
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Plammootil, Suma Mary. "Herstellung und Etablierung von 4-Hydroxytamoxifen aktivierbaren PKC[alpha]- [PKC alpha]-, PKC[beta]1- [PKC beta1] und PKCd--Fusionsproteinen [PKC delta-Fusionsproteinen]." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971703302.
Full textQueirolo, Valeria <1981>. "Caratterizzazione e ruolo di PKCε e PKCδ in modelli di differenziamento megacariocitario normale e patologico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6757/1/Queirolo_Valeria_tesi.pdf.
Full textProtein kinases C (PKC) are known to be ubiquitously distributed and to have pleiotropic effects. Isoforms epsilon (PKCε) and delta (PKCδ) are involved in the regulation of cell growth, survival and differentiation; in particular, they have been also investigated for their role in the hematopoiesis and in aberrant processes of differentiation along the erythroid and megakaryocytic lineages. In this PhD thesis, the results of an in vitro study about the role of these two kinases in models of megakaryocytic (MK) differentiation, both normal and pathological, are presented. The observations about PKCε and PKCδ kinetics show how these proteins have a specific modulation during the MK differentiation that results in an opposite pattern of expression and, in the murine model if compared with the human model, also a reciprocal one. In particular, in human megakaryocytopoiesis, PKCε results down-modulated, whereas in mouse its levels increase. Instead, PKCδ shows a high and steady expression in maturing CD34+ MK committed, but it is strongly down-modulated during the latest phases of platelet maturation in the murine model. The study also elucidates the different pathways PKCε and PKCδ work through, being an inhibitory action of PKCε on RhoA during proplatelets (ppt) formation in the mouse model while, in the human MK differentiation, platelets production is regulated by PKCδ through Bcl-xL. In this dissertation it is also demonstrated how in an aberrant megakaryocytopoiesis, as in the pathologic model of primary myeloproliferative neoplasm (PMF), PKCε is strongly deregulated and it results in an altered Bcl-xL expression. A forced down-modulation of this kinase restores a normal MK differentiation and ppt maturation. Therefore, the data presented show that PKCε and PKCδ play a key role in proper megakaryocyte maturation and that PKCε could be a potential new therapeutic target for PMF.
Queirolo, Valeria <1981>. "Caratterizzazione e ruolo di PKCε e PKCδ in modelli di differenziamento megacariocitario normale e patologico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6757/.
Full textProtein kinases C (PKC) are known to be ubiquitously distributed and to have pleiotropic effects. Isoforms epsilon (PKCε) and delta (PKCδ) are involved in the regulation of cell growth, survival and differentiation; in particular, they have been also investigated for their role in the hematopoiesis and in aberrant processes of differentiation along the erythroid and megakaryocytic lineages. In this PhD thesis, the results of an in vitro study about the role of these two kinases in models of megakaryocytic (MK) differentiation, both normal and pathological, are presented. The observations about PKCε and PKCδ kinetics show how these proteins have a specific modulation during the MK differentiation that results in an opposite pattern of expression and, in the murine model if compared with the human model, also a reciprocal one. In particular, in human megakaryocytopoiesis, PKCε results down-modulated, whereas in mouse its levels increase. Instead, PKCδ shows a high and steady expression in maturing CD34+ MK committed, but it is strongly down-modulated during the latest phases of platelet maturation in the murine model. The study also elucidates the different pathways PKCε and PKCδ work through, being an inhibitory action of PKCε on RhoA during proplatelets (ppt) formation in the mouse model while, in the human MK differentiation, platelets production is regulated by PKCδ through Bcl-xL. In this dissertation it is also demonstrated how in an aberrant megakaryocytopoiesis, as in the pathologic model of primary myeloproliferative neoplasm (PMF), PKCε is strongly deregulated and it results in an altered Bcl-xL expression. A forced down-modulation of this kinase restores a normal MK differentiation and ppt maturation. Therefore, the data presented show that PKCε and PKCδ play a key role in proper megakaryocyte maturation and that PKCε could be a potential new therapeutic target for PMF.
BONALUME, VERONICA. "GABAA RECEPTOR AS A NOVEL REGULATOR OF PERIPHERAL PAIN SENSITIVITY AND LOCAL NEURON-GLIA INTERACTION." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/699522.
Full textLe, Good Jessie Ann. "Regulation of atypical PKCs." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313738.
Full textKerai, Preeti. "Structural and functional characterisation of PKCI." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325029.
Full textCrossland, V. M. "Cell cycle specific recruitment of PKCε." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1352790/.
Full textPena, Darlene Aparecida. "Anticorpos conformacionais para PKCs clássicas e suas aplicações." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-17082016-074719/.
Full textThe protein kinase C family (PKC) is composed of ten isoenzymes, which are capable of phosphorylating serine and threonine amino acid residues. PKC activation involves conformational changes, such as removing the pseudo-substrate from the active site and binding of the enzyme to lipids in biological membranes. In addition, PKC undergoes three phosphorylations that are important for the maturation/ folding of the enzyme and are not linked with activation status. Despite the fact that these kinases are involved in various pathological processes, such as carcinogenesis and cardiovascular disease, a relationship between PKC activation status with these diseases has not yet been established. This is partly due to the lack of tools to detect active PKC in tissue samples. In this thesis, based on conformational changes suffered by PKC during its activation, two antibodies against active cPKCs were rationally developed; a polyclonal antibody (anti-C2Cat) and a monoclonal (4.8E). Anti-C2Cat was produced after immunization of rabbits with a peptide located at the interface between the C2 and catalytic domains of cPKCs in an inactive PKC. The monoclonal antibody 4.8E was produced after immunization of Balb/C mice with total lysates from HEK293T cells overexpressing constitutively active forms of PKCβI. The anti-C2Cat and 4.8E specificity by active cPKCs was demonstrated by ELISA and immunoprecipitation assays, where the antibodies always showed higher affinity to active cPKCs. Anti-C2Cat was able to detect the temporal and spatial dynamics of cPKC activation upon receptor (morphine, ATP or glutamate) or phorbol ester stimulation in neuroblastoma lines (Neuro-2A and SK-N-SH). Futhermore, anti-C2Cat is able to detect active PKC in human tissues. Higher levels of active cPKC were observed in the more aggressive triple negative breast cancer tumors as compared to the less aggressive estrogen receptor positive tumors. Also, both antibodies were applied to study signaling pathways that lead to carcinogenesis in MDA-MB-231 cells by performing co-immunoprecipitation and mass spectrometry. Using this approach, the results suggest that active cPKCs may be involved in translation of proteins involved in cell migration, such as actin. Taken together, the results obtained in this thesis showed two rational ways to develop antibodies against active cPKCs and some applications for these tools were demonstrated. Strategies based on conformational changes, similar to those presented herein may be used for rational production of antibodies against other kinases and proteins.
McCarthy, Joy. "PKCε and cardioprotection : an exploration of putative mechanisms." Doctoral thesis, University of Cape Town, 2006. http://hdl.handle.net/11427/3429.
Full textRecent studies have investigated the underlying regulatory mechanisms that may explain the cardioprotective role of PKCε. Sub-proteome analysis has identified interactions between activated PKCε and various mitochondrial proteins, which orchestrate mitochondrial homeostasis, including proteins governing mitochondrial oxidative phosphorylation, electron transfer, ion transport and control of mitochondrial permeability transition (MPT). MPT disruption is regarded as a key step in the initiation of an apoptotic cascade. However, brief pore opening may be beneficial in triggering the generation of small amounts of protective reactive oxygen species (ROS) and restoring calcium homeostasis. PKCε also interacts with adenine nucleotide translocases (ANTs), inner mitochondrial membrane proteins essential for ATP production and an integral component of the permeability transition pore. An augmented capacity to generate ATP would fundamentally enhance resilience to ischemia.
Snider, Adam K. "PKC gamma regulates connexin 57." Thesis, Manhattan, Kan. : Kansas State University, 2010. http://hdl.handle.net/2097/4128.
Full textBahte, Svenja-Katharina Paula. "Identifikation neuer Bindungspartner von PKC- d [PKC-delta] mit Hilfe des Yeast-two-hybrid-Screens." [S.l.] : [s.n.], 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=013081490&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Full textQuittau-Prévostel, Corinne. "Mutant D294G de la PKC[alpha] tumorigénèse humaine : la PKC[alpha], un nouveau suppresseur de tumeur." Montpellier 1, 1997. http://www.theses.fr/1997MON1T005.
Full textGobbi, Giuliana <1971>. "Il ruolo della PKCε nel differenziamento eritroide e megacariocitario." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/313/1/TESI_GOBBI_.pdf.
Full textGobbi, Giuliana <1971>. "Il ruolo della PKCε nel differenziamento eritroide e megacariocitario." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/313/.
Full textGaboardi, Gian Carlo <1978>. "Ruolo della PLCγ1 e della PKCε nel differenziamento miogenico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/1076/1/Tesi_Gaboardi_Gian_Carlo.pdf.
Full textGaboardi, Gian Carlo <1978>. "Ruolo della PLCγ1 e della PKCε nel differenziamento miogenico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/1076/.
Full textZINI, SILVIA. "PKC: Paffard Keatinge-Clay architetto itinerante." Doctoral thesis, Università IUAV di Venezia, 2015. http://hdl.handle.net/11578/278352.
Full textBurguière, Eric. "Rôle de la DLT cérébelleuse hétérosynaptique des fibres parallèles dans la navigation." Paris 6, 2006. https://tel.archives-ouvertes.fr/tel-00129346.
Full textGresham, Rebecca. "The role of PKCι in cell polarity, mitosis and cancer." Thesis, University of Bath, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.545318.
Full textWorthmann, Kirstin [Verfasser]. "Die Rolle der atypischen Protein Kinase C Isoformen PKC[lambda]/[iota] und PKC[zeta] in Podozyten / Kirstin Worthmann." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover, 2011. http://d-nb.info/1012625508/34.
Full textCabrerizo, Benito Yolanda. "Studies on a PKC-PLD-MAPK pathway." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399767.
Full textKostelecky, B. D. "An investigation of PKC isoform functional specificity." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18705/.
Full textRoberts, Sarah Anne. "An investigation of protein kinase C in Swiss 3T3 cells using phorbol esters." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369190.
Full textDovas, Athanassios. "Regulation of RhoA by PKCa during syndecan-4-mediated cell adhesion." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434916.
Full textLamy, Carole. "Synthèse de fluoroalcènes et disaccharides comme peptidomimétiques visant l'interaction PKCε-RACK." Lyon 1, 2008. http://www.theses.fr/2008LYO10049.
Full textThe protein kinase C family has been implicated in the transduction of a large variety of cellular signals between the receptor and the intracellular machinery that will be responsible for the desired action. This has led to a considerable interest in the inhibition of PKC, in particular in the inhibition of single isoforms of PKC. A novel approach consists of targeting the localization of PKC on the cytoplasmic membrane, rather than the enzyme itself, by inhibiting the interaction of PKC with its receptor, RACK-2. The objective of this work is the design and synthesis of fluoroalkene and disaccharide-based peptidomimetics of the octapeptide EAVSLKPT, an inhibitor of the PKCε-RACK interaction reported by Mochly Rosen et al. The fluoroalkene peptidomimetics were synthesized by a route inspired by Waelchli’s synthesis of unfunctionalized peptidomimetics of the parathyroïd hormone. The second family of peptidomimetics was designed based on a disaccharide scaffold. This skeleton offers a semi-rigid backbone with several well defined conformations around the aglyconic bond, ten functionaliseable positions, and a sufficient size to mimic a relatively linear peptide chain. Pharmacophore modeling and conformational analysis allowed us to identify a particular saccharide, a D-glucose β(1-3) L-Glucose substituted at the 4 position with a tetrahydropyran and the 3’ position with a carboxy-bearing chain, which matched the peptide pharmacophores in a favorable solution conformation
ZECCHINI, Erika. "Oxidative stress in health and disease: role of PKCζ and p66Shc." Doctoral thesis, Università degli studi di Ferrara, 2010. http://hdl.handle.net/11392/2389327.
Full textPeel, N. R. "Dissecting compartmentalised atypical PKC controls in cell migration." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1419046/.
Full textGumpert, Nicolas Maximilian. "Funktionale Bedeutung der Protein Kinase C - d [C - delta] (PKC - d) [(PKC - delta)] in der Reorganisation der zytoskelettären Architektur humaner Keratinozyten." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=964885824.
Full textMartín, Flix Marta. "Inestabilitat cromosòmica i radiosensibilitat en cèl·lules defectives en ATM i DNA-PKcs." Doctoral thesis, Universitat Autònoma de Barcelona, 2008. http://hdl.handle.net/10803/3817.
Full textL'objectiu d'aquesta tesi doctoral és determinar quins factors contribueixen de manera específica a la radiosensibilitat i a la inestabilitat cromosòmica de les cèl·lules deficients en ATM i en DNA-PKcs. Per assolir aquest objectiu es va analitzar: (1) l'espectre d'aberracions radio-induïdes en ambdós tipus cel·lulars; (2) l'evolució i resolució d'aquestes aberracions al llarg del temps; (3) la possible implicació del metabolisme telomèric en aquestes aberracions i (4) la cinètica de reunió de DSBs de les cèl·lules deficients en ATM i la de les cèl·lules deficients en DNA-PKcs.
Després de ser irradiats, ambdós tipus cel·lulars acumulen un nombre significativament elevat d'aberracions cromosòmiques. El metabolisme telomèric només contribueix de manera marginal a la inestabilitat cromosòmica en cèl·lules deficients en DNA-PKcs i no té repercussions en la línia cel·lular deficient en ATM emprada en aquest estudi. En analitzar la cinètica de reunió dels DSBs radio-induïts es va fer palès que la deficiència en DNA-PKcs indueix un alentiment de la mateixa. Una reparació més lenta de les lesions en el DNA afavoreix (1) l'acumulació de fragments cromosòmics i, alhora, (2) la reunió il·legítima dels mateixos. La cinètica alentida explica l'ampli espectre d'aberracions radio-induïdes obtingut en aquestes cèl·lules així com la seva persistència en el temps, esdevenint el principal factor responsable de la radiosensibilitat i inestabilitat cromosòmica en cèl·lules deficients en DNA-PKcs. En canvi les cèl·lules deficients en ATM reparen la majoria dels DSBs radio-induïts amb una cinètica comparable a la de les cèl·lules normals, però una fracció dels trencaments roman sense reparar inclús a llargs temps post-irradiació. Per tant, l'acumulació de trencaments pendents de ser reparats a llargs temps post-irradiació (48 i 72 h) apareix com el principal factor responsable de la radiosensibilitat i inestabilitat cromosòmica d'aquestes cèl·lules. Però com s'explica la persistència d'aquests trencaments durant vàries divisions post-irradiació? Un cop descartat un alentiment de la cinètica de reparació ens varem plantejar la possibilitat de que l'absència d'ATM impedís la correcta detecció d'aquests DSBs. Per tal d'avaluar aquesta hipòtesi es va realitzar un anàlisi de la presència de γH2AX i Mre11 en els extrems cromosòmics trencats. La majoria de les delecions cromosòmiques presents en les cèl·lules deficients en ATM presenten marcatge amb les dues proteïnes en el punt de trencament, però una fracció considerable de les mateixes (25%) no presenta cap tipus de marcatge. El resultat obtingut suggereix que els trencaments no senyalitzats no estan essent correctament detectats i que la maquinària de reparació no és activa en ells. Proposem que l'acumulació de trencaments pendents de reparar són una característica de les cèl·lules deficients en ATM, i que aquesta acumulació contribueix de manera important a la seva radiosensibilitat i inestabilitat cromosòmica. Mentre que la fracció de trencaments correctament senyalitzats per γH2AX i Mre11 podrà ser reparada al llarg del temps, la fracció de trencaments sense senyalitzar podria romandre sense reparar durant temps indefinit, contribuint especialment a la inestabilitat cromosòmica d'aquestes cèl·lules.
ATM (Ataxia-Telangiectasia Mutated) and DNA-PKcs (DNA-dependent Protein Kinase, catalytic subunit) belong to the PIKKs (PhosphatidylInositol 3-Kinase-related Kinase) family, and both proteins develop important functions in the DNA damage response pathway (DDR). ATM and DNA-PKcs are activated by the presence of DNA double strand breaks (DSBs), which are produced by multiple factors, ionizing radiations among these. Once activated, both kinases display different -but significantly complementary- functions in the DDR: ATM is able to: (1) halt the cell cycle; (2) activate several proteins implicated in the homologous repair pathway (HR) and (3) if the cell harbours massive and/or irreparable damage, ATM can initiate the apoptosis pathway. Meanwhile, DNA-PKcs is a master protein belonging to the non homologous end joining repair pathway (NHEJ), where it activates and regulates the remaining factors implied in this repair pathway. Finally, if the cell carries extensive damage DNA-PKcs can also induce the apoptosis pathway. Individuals affected by the absence of either kinase develop chromosomal instability syndromes, which are characterized by a special cancer predisposition. Cells obtained from the affected individuals are extremely radiosensitive and accumulate chromosomal aberrations.
The main goal of this doctoral thesis is to determine which factors specifically contribute to the radiosensitivity and chromosomal instability of ATM and DNA-PKcs deficient cells. In order to attain this goal we analyzed: (1) the spectrum of radio-induced aberrations in both cell types; (2) the evolution and resolution of these aberrations over time; (3) the possible implication of telomeric metabolism in these aberrations and (4) the DSBs joining kinetics of ATM and DNA-PKcs deficient cells.
After irradiation both cellular types accumulate a significant number of chromosomal aberrations. While telomeric metabolism contributes -although only marginally- to the chromosomal instability in DNA-PKcs deficient cells, it has no influence on the ATM deficient cell line employed in this study. Analysis of the DSBs joining kinetics demonstrates that DNA-PKcs deficiency induces a delay in the repair kinetics of radio-induced lesions. Slower DNA repair favours the accumulation of chromosomal fragments as well as their illegitimate joining displayed by DNA-PKcs deficient cells. Thus, the slower repair kinetics explain the broad aberration spectrum obtained in these cells, as well as their persistence in time, revealed to be the main factor responsible for radiosensitivity and chromosomal instability in DNA-PKcs deficient cells. On the other hand, ATM deficient cells are able to repair the majority of the radio-induced DSBs with normal joining kinetics except for a fraction of breaks, which remain unrepaired even at long post-irradiation times. Therefore, the accumulation of unrepaired breaks at long post-irradiation times (48 and 72 hr) is revealed to be the main factor responsible for the radiosensitivity and chromosomal instability of AT cells. But how can the persistence of these breaks in an unrepaired state during several cell divisions be explained? After discarding a delayed DSBs joining kinetic, we reflected upon the possibility of the absence of ATM preventing proper detection of unrepaired DSBs. In order to evaluate this hypothesis we analysed the presence of γH2AX and Mre11 signalling in the broken chromosome ends scored in AT cells. The majority of the chromosome deletions displayed both γH2AX and Mre11 labelling at the break point, but a significant fraction (25%) was devoid of any labelling. The results obtained suggest that unlabelled breaks are not being correctly detected and that the cell repair machinery is not active on them. We propose that the accumulation of breaks waiting for efficient repair is a hallmark of ATM deficient cells, and that this accumulation makes a major contribution to their radiosensitivity and chromosomal instability. While the fraction of correctly γH2AX and Mre11-labelled breaks will eventually be repaired, the fraction of unlabelled breaks remains invisible to the DNA damage repair machinery, thus especially contributing to the chromosomal instability of these cells.
Meng, Zhigang [Verfasser]. "Identification of PKCα as a CK1δ C-terminal targeting kinase / Zhigang Meng." Ulm : Universität Ulm, 2016. http://d-nb.info/1106329945/34.
Full textQian, Yu. "Analyser le gène PKC-2 chez Caernorhabditis elegans et crible les mutants contre sérotonine chez le C. elegans souche pkc-2 (ok328)." Phd thesis, Université Claude Bernard - Lyon I, 2009. http://tel.archives-ouvertes.fr/tel-00712129.
Full textAaltonen, V. (Vesa). "PKC and neurofibromin in the molecular pathology of urinary bladder carcinoma:the effect of PKC inhibitors on carcinoma cell junctions, movement and death." Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514285899.
Full textHessabi, Tarik. "Über die Rolle von PKC epsilon während der Wundheilung." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=977243265.
Full textGarratt-Lalonde, Michelle. "The role of atypical PKC iota in glioblastoma multiforme." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26484.
Full textEttinger, Susan Lorraine. "Cytokine-induced activation of PKC isoenzymes in hemopoietic cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ27139.pdf.
Full textNakagawa, Rinako. "Role of PKC during B cell development and transformation." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/9056/.
Full textCourtellemont, Thibault. "Septin regulation by the Protein Kinase C in the budding yeast, Saccharomyces cerevisiae." Thesis, Montpellier 2, 2014. http://www.theses.fr/2014MON20007/document.
Full textCytokinesis is the last step of mitosis and is the fundamental process leading to the physical separation of two daughter cells. Defects in cytokinesis generate polyploid cells that are prone to chromosome missegregation and cancer development. In animal cells and fungi, cytokinesis requires the formation and contraction of an actomyosin ring that drives ingression of the cleavage furrow. Additional cytoskeletal proteins called septins contribute to cytokinesis. In the budding yeast Saccharomyces cerevisiae, five different septins are expressed during the mitotic cell cycle (Cdc3, Cdc10, Cdc11, Cdc12 and Shs1). All septins, except for Shs1, are essential for cell viability. Yeast septins form filaments that in turn organize into a ring at the bud neck, which is the constriction between the mother and the future daughter cell where cytokinesis takes place. The septin ring then expands into a rigid septin collar that acts as scaffold for cytokinesis by recruiting most cytokinetic proteins to the bud neck. Cell cycle-regulated changes in septin ring dynamics are thought to be important for its cytokinetic functions and formation of the rigid septin collar is accompanied by septin phosphorylation. However, the kinases responsible for these modifications have not been fully characterized. Unpublished data from our laboratory indicate that the Rho1 GTPase, which is essential for actomyosin ring formation and contraction, and its target protein kinase C (Pkc1) contribute to deposition and stabilization of the septin ring. Here, we have addressed how Pkc1 regulates septin ring deposition and/or stability. To this end, septin complexes were purified from yeast and analyzed by mass spectrometry, comparing wild type and pkc1Δ mutant cells. This mass spectrometry analysis clearly showed that phosphorylation of a cluster of residues in Shs1 decreased in the absence of Pkc1. Interestingly, we found that this cluster is conserved in the septin Cdc11, which together with Shs1 is known to play an important role in the assembly of high-order structures like filaments and rings. Phosphomimetic mutations of the phosphorylatable cluster in Shs1 have been previously shown to disrupt filament formation in-vitro. We therefore proceeded to mutagenise the same cluster in Cdc11, generating a phosphomimetic (CDC11-9D) and in a non-phosphorylatable mutant (CDC11-9A). Strikingly, the phosphomimetic CDC11-9D caused cytokinesis defects in cells lacking Shs1, whereas the non-phosphorylatable CDC11-9A allele partially rescued the sickness of shs1∆ mutant cells. These observations are in agreement with the notion that Cdc11 and Shs1 share overlapping functions and highlight an important role of the phosphorylatable cluster of Cdc11 for cytokinesis. We also found that Pkc1 does not phosphorylate septins directly, but rather regulates the activity of septin kinases and phosphatases. Consistently, we show that Pkc1 affects the interaction between septins and the bud neck kinase Gin4, which is known to interact with septins and to phosphorylate them. In addition, Pkc1 impacts on the phosphorylation of two additional bud neck kinases, Hsl1 and Kcc4, which are part of the same family of Nim1-related kinases as Gin4. In addition, PKC1 deletion leads to a dramatic decrease in the levels of Kcc4 , so that it is barely detected at the bud neck.Deletion of PKC1 affects also the interaction between septins and the Bni4 protein, which is a regulatory subunit for the PP1 phosphatase at the bud neck. In turn, we found that Bni4-PP1 modulates Cdc11 phosphorylation, thereby explaining how the latter is decreased in the absence of Pkc1. Altogether, our data strongly suggest that Pkc1 is a novel major regulator of septins in yeast
Mermet-Joret, Noëmie. "Etude du développement postnatal des interneurones de la couche II interne dans le sous-noyau caudal du trijumeau chez le rat." Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1DD02.
Full textThe first postnatal weeks are pivotal for the development of pain sensitivity and are associated with structural and functional reorganization of sensory systems. Interneurons located in the inner part of lamina II(IIi) of the caudal trigeminal subnucleus (Sp5C), the first central node in orofacial tactile and nociceptive pathways, are key elements in circuits underlying the orofacial mechanical allodynia. The aim of this thesis is to study the morphological (by using immunohistochemistry and tridimensional morphological analysis) and functional (by using whole-cell patch-clamp recordings) postnatal development of these interneurons. First, we looked at a very specific population of lamina IIi interneurons expressing the gamma isoform of the protein kinase C (PKCγ). At the earliest stage of our study (3 postnatal days, P3), PKCγ interneurons are present in all superficial layers but PKCγ interneurons can be observed in lamina IIi only at P6. The number of PKCγ interneurons within this lamina then increases gradually up to P11-15. At this age, the number of PKCγ interneurons in lamina IIi is almost the same as that at later ages. Interestingly, we show that neither cell proliferation nor the gradual projection of nociceptive fibers within the Sp5C accounts for such increase. We also studied the development of the whole population of lamina IIi interneurons. These interneurons undergo a large number of morphological changes, in their soma (increased volume) as well as neurites (concomitant increase in length and decrease in number and branching). Furthermore, according to electrophysiological properties, lamina IIi interneurons, at birth, are more depolarized, have a lower rheobase – suggesting that they are more excitable – and exhibit more frequently a single action potential discharge profile compared with mature ones. All these structural and functional changes of lamina IIi interneurons might contribute to the development of orofacial sensitivity
Palmer, Romy [Verfasser]. "Untersuchung von PKCα als Schlüsselprotein der β-Arrestin2 vermittelten Nephrin-Endozytose / Romy Palmer." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1053761619/34.
Full textDuarte, Mariana Lemos. "Identificação e validação funcional de novos alvos das PKCs em célula tronco embrionária." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-16012014-105728/.
Full textSome of the strategies used to understand stem cell biology are based on the identification of signalling cascades that lead to differentiation and self-renewal of embryonic stem cells (ESC) by selective interference of specific signalling processes. The protein kinase C (PKC) family is known to participate in ESC self-renewal and differentiation, however, the specific role of the different PKC isoenzymes in these cells remains to be determined. Therefore, we investigated the role of atypical PKCs (aPKC) in undifferntiated ESC using a specific inhibitor for these serine/ threonine kinases, pseudo-substrate peptide of aPKCs, and phosphoproteomics. The majority of proteins whose phosphorylation decreased upon aPKC inhibition, are proteins involved in metabolism in particular with the glycolytic pathway. Besides that, inhibiton of aPKCs led to a decrease in glucose uptake and lactate secretion, followed by a decrease in lactate dehydrogenase activity, and an increase in mitochondrial activity as measured by oxygen consumption after treatment with olygomycin and a chemical uncoupler. We also verified that aPKCs are able to directly phosphorylated pyruvate kinase. Aerobic glicolysis seems to be fundamental for the maintainance of undifferentiated ESC, and we demonstrated that aPKCs participte in these processes helping to maintain self-renewal of undifferentiated ESC. We also observed that aPKCs as PKCβI modulate the phosphorylation of α-tubulin, however, while aPKCs interact with α-tubulin during interfase PKCβI interacts with α-tubulin only during mitosis. These results lead to the second part of this thesis. We investigated the role of α-tubulina phosphorylation by PKCβI. Indentifying threonine 253, a conserved residue in several vertebrate species, of localized at the polymerization interface between α- and β-tubulin, as a phosphorylation site of α-tubulin by PKCβI. This site is not in a linear consensus for PKC, however, it is in a structuraly formed consensus, where basic aminoacids distant in the linear sequence are juxtaposed in the three dimentional protein structure. Simulation studies by molecular dynamics show that the interaction between α and β-tubulin increases upon this phosphorylation, once, phosphorylated T253 interacts with com K105, a conserved residue in β-tubulin. The in vitro phosphorylation of α-tubulin increased tubulin polymerization rate and inhibiton of PKCβI in cells reduced repolimeration rate of microtubles upon treatment with nocodazole. Besides that, the importance of this phosphorylation site were demonstrated by the fact that a phosphomimetic mutant GFP-α-tubulina, T253E is more incorporated in mitotic fuses while T253A is less than wild type. Our data support the hypothesis that structural consensus may be important sites recognized and that T253 phosphorylation of α-tubulin afects the polymer stability. In conclusion, using phosphoproteomics methods and selective interference of signal transduction pathways combined with experimental validation studies of the identified targets we can propose roles for aPKCs and PKCβI in undifferentiated ESC.
Kelly, Joanna. "Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10045030/.
Full textEl, Houfi Younas. "PKCα interagit avec la sous-unité catalytique de la m1A58 ARNt méthyltransférase Trm6-Trm61." Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON1T008/document.
Full textProtein kinase C alpha (PKCα) is a ubiquitous serine/threonine kinase. It is involved in the regulation of various cellular functions by interacting with many intracellular proteins. Among these, we were able to identify Trm61, the catalytic subunit of the tRNA m1A58 methyltransferase which plays an essential role in the stability of the tRNAiMet. Localization studies of PKCα, Trm6 and Trm61 demonstrated that these two subunits do not always share the same subcellular compartment: while Trm6 is strictly nuclear, Trm61 is both in the nucleus and in the cytoplasm where it co-localizes with PKCα. We also provided the evidence that the increased expression of PKCα induces a decrease in that of Trm61, while reduced PKCα expression is accompanied by an increase in both Trm61 and tRNAiMet levels. These changes in expression are accompanied by a significant increase in cell proliferation at high-density. This work has also shown that Trm61 subunit is essential for the survival of the C6 glioma cell line. Our results suggest that Trm6 is the essential determinant of functional tRNA m1A58 methyltransferase level and we discuss the possibility of a secondary role for cytoplasmic Trm61 in the regulation of the proliferation independently of Trm6-Trm61 action. Interestingly, human grade II and III gliomas expressed higher levels of PKCα mRNA than glioblastomas and inversely for TRM6 and TRM61 mRNA levels, arguing for a relevance of our observations for human gliomagenesis
Bom, Vinícius Leite Pedro. "A importância da proteína fosfatase sitA na adesão, integridade da parede celular, biofilme e virulência de Aspergillus fumigatus." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17131/tde-20072016-092319/.
Full textAspergillus fumigatus is an opportunistic pathogenic fungus able to infect immunocompromised patients causing eventually disseminated infections that are difficult to be controlled, and lead to high mortality rates. It is important to understand how are orchestrated the signalling pathways that regulate these factors involved in virulence. Protein phosphatases are central to numerous signal transduction pathways. Here we characterize A. fumigatus protein phosphatase 2A SitA, the S. cerevisiae Sit4p homologue. The sitA gene is not an essential gene and we were able to construct an A. fumigatus null mutant. The ?sitA strain had increased MpkA phosphorylation, was more sensitive to cell wall damaging agents, had increased ??1,3?glican and chitin, and was impaired in biofilm formation. The ?sitA strain is more sensitive to several metals and ions such as MnCl2, CaCl2, and LiCl, however, it is more resistant to ZnSO4. The ?sitA strain was avirulent in a murine model of invasive pulmonary aspergillosis. These results stress the importance of A. fumigatus SitA as a possible modulator of PkcA/MpkA activity and its involvement in the cell wall integrity pathway
Kumar, Varun. "Protein Kinase C Signaling in Neurodegeneration." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1455721051.
Full textDykes, Ava Caudill. "Diverse roles of PKC[alpha] in vascular smooth muscle contraction." Huntington, WV : [Marshall University Libraries], 2006. http://www.marshall.edu/etd/descript.asp?ref=680.
Full textTitle from document title page. Includes abstract. Document formatted into pages: contains xiii, 122 p. including illustrations. Bibliography: Chap.I. p.28-33; Chap. II. p. 82-86; Chap. III p.115-116.
Brandt, Dominique. "Über die Rolle von PKC bei der Reorganisation des Zytoskeletts." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968536875.
Full textHall, Kellie Joann. "The Regulation and Role of Novel PKC Isoforms in Platelets." Thesis, University of Bristol, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486072.
Full textClelland, Lyndsay Jacquelyn. "Role of ROK and PKC in Permeabilized Rabbit Femoral Artery." VCU Scholars Compass, 2007. http://hdl.handle.net/10156/1581.
Full textRao, Sudha. "Identification and characterisation of a novel form of PKC-zeta." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312797.
Full textScott, Hannah Elizabeth. "PKC-δ, its C2 domain and breast cancer cell lines." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12668/.
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