Academic literature on the topic 'PRKCδ'
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Journal articles on the topic "PRKCδ"
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Arenas, Ailan F., Gladys E. Salcedo, and Jorge E. Gomez-Marin. "R Script Approach to Infer Toxoplasma Infection Mechanisms From Microarrays and Domain-Domain Protein Interactions." Bioinformatics and Biology Insights 11 (January 1, 2017): 117793221774725. http://dx.doi.org/10.1177/1177932217747256.
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Pathogen-host protein-protein interaction systems examine the interactions between the protein repertoires of 2 distinct organisms. Some of these pathogen proteins interact with the host protein system and may manipulate it for their own advantages. In this work, we designed an R script by concatenating 2 functions called rowDM and rowCVmed to infer pathogen-host interaction using previously reported microarray data, including host gene enrichment analysis and the crossing of interspecific domain-domain interactions. We applied this script to the Toxoplasma-host system to describe pathogen survival mechanisms from human, mouse, and Toxoplasma Gene Expression Omnibus series. Our outcomes exhibited similar results with previously reported microarray analyses, but we found other important proteins that could contribute to toxoplasma pathogenesis. We observed that Toxoplasma ROP38 is the most differentially expressed protein among toxoplasma strains. Enrichment analysis and KEGG mapping indicated that the human retinal genes most affected by Toxoplasma infections are those related to antiapoptotic mechanisms. We suggest that proteins PIK3R1, PRKCA, PRKCG, PRKCB, HRAS, and c-JUN could be the possible substrates for differentially expressed Toxoplasma kinase ROP38. Likewise, we propose that Toxoplasma causes overexpression of apoptotic suppression human genes.
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Tweedell, Rebecca, Le Qi, Zhaoli Sun, and Rhoel Dinglasan. "Kupffer Cells Survive Plasmodium berghei Sporozoite Exposure and Respond with a Rapid Cytokine Release." Pathogens 7, no. 4 (November 24, 2018): 91. http://dx.doi.org/10.3390/pathogens7040091.
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The liver stage of the Plasmodium life cycle features sporozoite traversal of the liver sinusoidal barrier through Kupffer cells (KCs) followed by invasion of hepatocytes. Little is known about the interaction of Plasmodium sporozoites with KCs, the liver-resident macrophages. Previous reports suggest KCs do not mount a pro-inflammatory response and undergo cell death following this interaction. Our work explores this interaction using primary rat KCs (PRKCs) and Plasmodium berghei sporozoites. We analyzed PRKC culture supernatants for markers of an immunological response through cytokine arrays. Additionally, cell wounding and death were assessed by monitoring lactate dehydrogenase (LDH) levels in these supernatants and by live/dead cell imaging. We found that PRKCs mount an immunological response to P. berghei sporozoites by releasing a diverse set of both pro- and anti-inflammatory cytokines, including IFNγ, IL-12p70, Mip-3α, IL-2, RANTES, IL-1α, IL-4, IL-5, IL-13, EPO, VEGF, IL-7, and IL-17α. We also observed no difference in LDH level or live/dead staining upon sporozoite exposure, suggesting that the KCs are not deeply wounded or dying. Overall, our data suggest that sporozoites may be actively modulating the KC’s reaction to their presence and altering the way the innate immune system is triggered by KCs.
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Ricchiuti, Vincent, Christine G. Lian, Eveline M. Oestreicher, Loc Tran, James R. Stone, Tham Yao, Ellen W. Seely, Gordon H. Williams, and Gail K. Adler. "Estradiol increases angiotensin II type 1 receptor in hearts of ovariectomized rats." Journal of Endocrinology 200, no. 1 (October 17, 2008): 75–84. http://dx.doi.org/10.1677/joe-08-0199.
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We tested the hypothesis that 17β-estradiol (E2) has dual effects on the heart, increasing levels of proteins thought to have beneficial cardiovascular effects (e.g. endothelial nitric oxide (NO) synthase (eNOS)) as well as those thought to have detrimental cardiovascular effects (e.g. type 1 angiotensin II (AngII) receptor (AT1R)). Ovariectomized Wistar rats consuming a high-sodium diet received one of four treatments (n=7 per group): group 1, placebo pellets; group 2, E2(0.5 mg/pellet, 21-day release); group 3, NOS inhibitor,Nω-nitro-l-arginine-methyl-ester (l-NAME; 40 mg/kg per day for 14 days) plus Ang II (0.225 mg/kg per day on days 11–14); group 4, E2plusl-NAME/Ang II. E2increased cardiac levels of estrogen receptors ESR1 and ESR2, an ESR-associated membrane protein caveolin-3, eNOS, and phosphorylated (p)eNOS, thus, exerting potentially beneficial cardiovascular effects on NO. However, E2also increased cardiac levels of proteins associated with cardiovascular injury and inflammation including, AT1R, protein kinase C delta (PRKCD), phosphorylated PRKC, and phosphorylated extracellular signal regulated kinase (pMAPK)3/1, plasminogen activator inhibitor-1 (PAI-1), osteopontin and ED-1, a monocyte/macrophage-specific protein. E2treatment led to similar protein changes in the hearts ofl-NAME/Ang II-treated rats except that the increase in peNOS was prevented, andl-NAME/Ang II and E2had additive effects in increasing cardiac PRKCD and PAI-1. Thus, the highest levels of cardiac PAI-1 and PRKCD occurred inl-NAME/Ang II-treated rats receiving E2. In summary, E2treatment increased cardiac expression of AT1R as well as the expression of pro-inflammatory and prothrombotic factors.
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Liu, Fangzhou, Yuanbai Li, Meng Li, Jing Wang, Yiying Zhang, Yu Du, and Yang Yang. "Study on Mechanism of Iridoid Glycosides Derivatives from Fructus Gardeniae in Jiangxi Province by Network Pharmacology." Evidence-Based Complementary and Alternative Medicine 2020 (June 27, 2020): 1–12. http://dx.doi.org/10.1155/2020/4062813.
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Objective. To investigate the pharmacological mechanism of the iridoid glycosides from Fructus Gardeniae in Jiangxi province by network pharmacology. To provide a valuable research strategy for the rational use and in-depth research and development of Fructus Gardeniae from Jiangxi. Method. Previous research results of our group show that the contents of iridoid glycosides in Fructus Gardeniae from Jiangxi province have a significant difference compared with other regions (P<0.05). Based on our previous experimental results, this study selected six characteristic high-content bioactive iridoid glycosides components of Fructus Gardeniae from Jiangxi province as candidate components. TCMSP database was used to obtain the process parameters of absorption, distribution, metabolism, and excretion (ADME) of candidate components. PubChem and SWISS online database were used to predict the related targets. Cytoscape software was used to the construct compound-target-disease (C-T-D) network of the Fructus Gardeniae iridoid glycosides ingredients. Furthermore, the GO biological process analysis and the pathway enrichment analysis were carried out using the CTD online analysis platform; then, an illustrated network that contains the main “chemicals-targets-pathway (C-T-P)” was constructed to analyze main biological pathways for obtaining the deep mechanism of Fructus Gardeniae in Jiangxi. Results. 6 iridoid glycosides, namely geniposide, gardenoside, geniposidic acid, genipin 1-gentiobioside, gardoside, and shanzhiside, from Fructus Gardeniae in Jiangxi province were obtained as candidate components through previous work and network pharmacology screening. 36 corresponding targets were acted, such as BCL2, MAPT, F2, BCL2L1, PRKCD, PRKCB, HIF1A, and PRKCA. These targets could joint in pathways, such as signaling by GPCR, neuroactive ligand-receptor interaction, inflammatory mediator regulation of TRP channels, and ion channel transport. Interestingly, these pathways were highly associated with liver diseases, neurological diseases, hypertension, neoplasms, hyperalgesia, and inflammation. Remarkably, we boldly speculate that the Fructus Gardeniae from Jiangxi province can play a pharmacological role in hepatic encephalopathy through regulating multiple signaling pathways in an integrated manner. Conclusion. The method based on system pharmacology could help to find the key targets of characteristic high-content chemical constituents of herb from different producing areas, the signaling pathway and disease network of TCM, and provide useful information and data support for giving a further study on traditional Chinese medicine resources in different regions of China.
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Wang, Hao-Fan, Jian Jiang, Jia-Shun Wu, Mei Zhang, Xin Pang, Li Dai, Ya-Ling Tang, and Xin-Hua Liang. "Hypermethylation of PRKCZ Regulated by E6 Inhibits Invasion and EMT via Cdc42 in HPV-Related Head and Neck Squamous Cell Carcinoma." Cancers 14, no. 17 (August 27, 2022): 4151. http://dx.doi.org/10.3390/cancers14174151.
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Purpose: To study the role of target genes with aberrant DNA methylation in HPV+ HNSCC. Methods: A HumanMethylation450 BeadChip array (Illumina) was used to identify differentially methylated genes. CCK-8, flow cytometry, wound healing, and cell invasion assays were conducted to analyze the biological roles of PRKCZ. Western blot, qRT-PCR, immunohistochemistry, and animal studies were performed to explore the mechanisms underlying the functions of PRKCZ. Results: We selected PRKCZ, which is associated with HPV infection, as our target gene. PRKCZ was hypermethylated in HPV+ HNSCC patients, and PRKCZ methylation status was negatively related to the pathological grading of HNSCC patients. Silencing PRKCZ inhibited the malignant capacity of HPV+ HNSCC cells. Mechanistically, HPV might promote DNMT1 expression via E6 to increase PRKCZ methylation. Cdc42 was required for the PRKCZ-mediated mechanism of action, contributing to the occurrence of epithelial-mesenchymal transition (EMT) in HPV+ HNSCC cells. In addition, blocking PRKCZ delayed tumor growth in HPV16-E6/E7 transgenic mice. Cdc42 expression was decreased, whereas E-cadherin levels increased. Conclusion: We suggest that PRKCZ hypermethylation induces EMT via Cdc42 to act as a potent tumor promoter in HPV+ HNSCC.
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Yang, Qi-En, Manabu Ozawa, Kun Zhang, Sally E. Johnson, and Alan D. Ealy. "The requirement for protein kinase C delta (PRKCD) during preimplantation bovine embryo development." Reproduction, Fertility and Development 28, no. 4 (2016): 482. http://dx.doi.org/10.1071/rd14160.
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Protein kinase C (PKC) delta (PRKCD) is a member of the novel PKC subfamily that regulates gene expression in bovine trophoblast cells. Additional functions for PRKCD in early embryonic development in cattle have not been fully explored. The objectives of this study were to describe the expression profile of PRKCD mRNA in bovine embryos and to examine its biological roles during bovine embryo development. Both PRKCD mRNA and protein are present throughout early embryo development and increases in mRNA abundance are evident at morula and blastocyst stages. Phosphorylation patterns are consistent with detection of enzymatically active PRKCD in bovine embryos. Exposure to a pharmacological inhibitor (rottlerin) during early embryonic development prevented development beyond the eight- to 16-cell stage. Treatment at or after the 16-cell stage reduced blastocyst development rates, total blastomere numbers and inner cell mass-to-trophoblast cell ratio. Exposure to the inhibitor also decreased basal interferon tau (IFNT) transcript abundance and abolished fibroblast growth factor-2 induction of IFNT expression. Furthermore, trophoblast adhesion and proliferation was compromised in hatched blastocysts. These observations provide novel insights into PRKCD mRNA expression profiles in bovine embryos and provide evidence for PRKCD-dependent regulation of embryonic development, gene expression and post-hatching events.
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Parzefall, Thomas, Julia Schnoell, Laura Monschein, Elisabeth Foki, David Tianxiang Liu, Alexandra Frohne, Stefan Grasl, et al. "PRKCA Overexpression Is Frequent in Young Oral Tongue Squamous Cell Carcinoma Patients and Is Associated with Poor Prognosis." Cancers 13, no. 9 (April 25, 2021): 2082. http://dx.doi.org/10.3390/cancers13092082.
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Oral tongue squamous cell carcinomas (OTSCCs) have an increasing incidence in young patients, and many have an aggressive course of disease. The objective of this study was to identify candidate prognostic protein markers associated with early-onset OTSCC. We performed an exploratory screening for differential protein expression in younger (≤45 years) versus older (>45 years) OTSCC patients in The Cancer Genome Atlas (TCGA) cohort (n = 97). Expression of candidate markers was then validated in an independent Austrian OTSCC patient group (n = 34) by immunohistochemistry. Kaplan–Meier survival estimates were computed, and genomic and mRNA enrichment in silico analyses were performed. Overexpression of protein kinase C alpha (PRKCA) was significantly more frequent among young patients of both the TCGA (p = 0.0001) and the Austrian cohort (p = 0.02), associated with a negative anamnesis for alcohol consumption (p = 0.009) and tobacco smoking (p = 0.02) and poorer overall survival (univariate p = 0.02, multivariate p< 0.01). Within the young subgroup, both overall and disease-free survival were significantly decreased in patients with PRKCA overexpression (both p < 0.001). TCGA mRNA enrichment analysis revealed 332 mRNAs with significant differential expression in PRKCA-upregulated versus PRKCA-downregulated OTSCC (all FDR ≤ 0.01). Our findings suggest that PRKCA overexpression may be a hallmark of a novel molecular subtype of early-onset alcohol- and tobacco-negative high-risk OTSCC. Further analysis of the molecular PRKCA interactome may decipher the underlying mechanisms of carcinogenesis and clinicopathological behavior of PRKCA-overexpressing OTSCC.
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Rotman, T., N. Etkovitz, A. Spiegel, S. Rubinstein, and H. Breitbart. "Protein kinase A and protein kinase Cα/PPP1CC2 play opposing roles in the regulation of phosphatidylinositol 3-kinase activation in bovine sperm." REPRODUCTION 140, no. 1 (July 2010): 43–56. http://dx.doi.org/10.1530/rep-09-0314.
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In order to acquire fertilization competence, spermatozoa have to undergo biochemical changes in the female reproductive tract, known as capacitation. Signaling pathways that take place during the capacitation process are much investigated issue. However, the role and regulation of phosphatidylinositol 3-kinase (PI3K) in this process are still not clear. Previously, we reported that short-time activation of protein kinase A (PRKA, PKA) leads to PI3K activation and protein kinase Cα (PRKCA, PKCα) inhibition. In the present study, we found that during the capacitation PI3K phosphorylation/activation increases. PI3K activation was PRKA dependent, and down-regulated by PRKCA. PRKCA is found to be highly active at the beginning of the capacitation, conditions in which PI3K is not active. Moreover, inhibition of PRKCA causes significant activation of PI3K. Similar activation of PI3K is seen when the phosphatase PPP1 is blocked suggesting that PPP1 regulates PI3K activity. We found that during the capacitation PRKCA and PPP1CC2 (PP1γ2) form a complex, and the two enzymes were degraded during the capacitation, suggesting that this degradation enables the activation of PI3K. This degradation is mediated by PRKA, indicating that in addition to the direct activation of PI3K by PRKA, this kinase can enhance PI3K phosphorylation indirectly by enhancing the degradation and inactivation of PRKCA and PPP1CC2.
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Ondee, Thunnicha, Thiranut Jaroonwitchawan, Trairak Pisitkun, Joseph Gillen, Aleksandra Nita-Lazar, Asada Leelahavanichkul, and Poorichaya Somparn. "Decreased Protein Kinase C-β Type II Associated with the Prominent Endotoxin Exhaustion in the Macrophage of FcGRIIb−/− Lupus Prone Mice is Revealed by Phosphoproteomic Analysis." International Journal of Molecular Sciences 20, no. 6 (March 18, 2019): 1354. http://dx.doi.org/10.3390/ijms20061354.
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Dysfunction of FcGRIIb, the only inhibitory receptor of the FcGR family, is commonly found in the Asian population and is possibly responsible for the extreme endotoxin exhaustion in lupus. Here, the mechanisms of prominent endotoxin (LPS) tolerance in FcGRIIb−/− mice were explored on bone marrow-derived macrophages using phosphoproteomic analysis. As such, LPS tolerance decreased several phosphoproteins in the FcGRIIb−/− macrophage, including protein kinase C-β type II (PRKCB), which was associated with phagocytosis function. Overexpression of PRKCB attenuated LPS tolerance in RAW264.7 cells, supporting the role of this gene in LPS tolerance. In parallel, LPS tolerance in macrophages and in mice was attenuated by phorbol 12-myristate 13-acetate (PMA) administration. This treatment induced several protein kinase C families, including PRKCB. However, PMA attenuated the severity of mice with cecal ligation and puncture on LPS tolerance preconditioning in FcGRIIb−/− but not in wild-type cells. The significant reduction of PRKCB in the FcGRIIb−/− macrophage over wild-type cell possibly induced the more severe LPS-exhaustion and increased the infection susceptibility in FcGRIIb−/− mice. PMA induced PRKCB, improved LPS-tolerance, and attenuated sepsis severity, predominantly in FcGRIIb−/− mice. PRKCB enhancement might be a promising strategy to improve macrophage functions in lupus patients with LPS-tolerance from chronic infection.
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Qian, Yiguan, Yang Li, Luwei Xu, Ke Chen, Ning Liu, Xiaobing Yang, Qian Lv, et al. "Tumor Cell-Derived Exosomal circ-PRKCI Promotes Proliferation of Renal Cell Carcinoma via Regulating miR-545-3p/CCND1 Axis." Cancers 15, no. 1 (December 25, 2022): 123. http://dx.doi.org/10.3390/cancers15010123.
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Renal cell carcinoma (RCC) originates from the epithelial cells of the renal tubules and has a high degree of malignancy and heterogeneity. Recent studies have found that exosomes regulate intercellular communication via transferring various bioactive molecules, such as circular RNAs (circRNAs), which are critical for cancer progression. However, the role of tumor cell-derived exosomal circRNAs in RCC remains unclear. In this study, we reported the high expression of circ-PRKCI in RCC tissues and serum exosomes. We also found that circ-PRKCI could be transferred exosomally from highly malignant RCC cells to relatively less malignant RCC cells. Tumor cell-derived exosomal circ-PRKCI promoted the proliferation, migration, and invasion of RCC cells, while inhibiting their apoptosis. Mechanistically, we found that circ-PRKCI promoted the proliferation of RCC via the miR-545-3p/CCND1 signaling pathway. Our study is the first to report the potential mechanisms of tumor cell-derived exosomal circ-PRKCI in RCC. In conclusion, this study will provide a new understanding about the molecular mechanisms of RCC progression.
Dissertations / Theses on the topic "PRKCδ"
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Bisso, Andrea. "New microRNAS regulating the P53 signaling pathway." Doctoral thesis, Università degli studi di Trieste, 2010. http://hdl.handle.net/10077/3594.
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2008/2009A vast body of evidence from clinical and basic research studies has demonstrated that the p53 pathway acts as an essential barrier in preventing cancer onset and development. ------------------------ A vast body of evidence from clinical and basic research studies has demonstrated that the p53 pathway acts as an essential barrier in preventing cancer onset and development. p53 receives and integrates a wide variety of cytotoxic and genotoxic stress signals from upstream sensors translating them into different cellular outcomes, ranging from apoptosis, cell cycle arrest, se-nescence, DNA repair or other tumor-suppressive responses. p53 exerts its role mainly at the transcriptional level and its timely activation/inactivation in response to stress depends on a complex repertoire of post-translational modifications and interactions with proteins. The crucial role of the p53 pathway in tumor suppression is highlighted by the fact that almost all tumors select for its functional inactivation, either by directly mutating the p53 gene or by altering the expression and functions of key p53 regulators and effectors. Therefore, identification of cellular factors that modulate this pathway and that could be altered in cancer cells, thus allowing to eva-de p53 control, is crucial for understanding cancer development and for designing novel effecti-ve therapeutic approaches. In this context, the aberrant expression or function of microRNAs (miRNAs) might be highly relevant. microRNAs are small non coding RNAs that finely regulate gene expression by binding the 3’UTR of their target mRNAs, thus altering their translation, stability and localization. It has been shown that several miRNAs modulate critical cellular processes deregulated in cancer, ac-ting either as oncogenes or tumor suppressors. On this basis, the aim of this thesis has been the identification and characterization of novel miRNAs able to modulate p53 functions by altering either upstream regulators (i.e. stress-activated kinases) or cofactors of p53. With this purpose we initially selected a panel of twenty-one candidate oncogenic miRNAs from the literature. First, we tested these miRNAs in a functional screening for their ability to modula-te p53-dependent functions in response to cisplatin (apoptosis) and nutlin-3 (cell cycle arrest). Second, miRNAs were also screened for their ability to impair p53 transcriptional activity through a reporter-based assay. We identified five candidate miRNAs from the first approach, and three from the second. miR-26a was identified through both approaches, suggesting that it might repersent a critical modulator of p53 functions. We demonstrated that miR-26a overe-xpression is able to dampen p53 transcriptional activity towards several p53 target promoters (Bax, Pig3 and p21). Moreover, we have shown that miR-26a strongly reduces p53-dependent apoptosis upon DNA damage in different cell lines, to a similar extent as obtained by RNAi-mediated p53 knock-down. At the molecular level, we observed that miR-26a impairs p53 activation by targeting multiple stress-activated kinases that phosphorylate p53, such as ATM, HIPK2 and PKCδ. Accordingly, miR-26a reduces p53 phosphorylation on Ser15 and Ser46 upon DNA damage. As a consequen-ce, miR-26a overexpression allows cells to proliferate in the presence of oncogenic stress, bypassing the induction of senescence (OIS) driven by RASV12 oncogene similar to what obtai-ned by knockdown of either p53 or its activationg kinase ATM. Considering our data and the reports describing miR-26a overexpression in several tumors (e.g. glioblastomas), we speculate that aberrant expression of miR-26a might represent an oncogenic process by preventing activation of the p53 pathway and thus relieving a primary barrier against transformation. For all these reasons, the perspective to block miR-26a expression/functions could represent a new important way to tackle tumors.
XXI Ciclo
1981
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Foulquier, Elodie. "Du métabolisme carboné à la morphogenèse : Rôle interprété par YvcK, protéine de Bacillus subtilis." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX22077.
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La protéine de fonction inconnue, YvcK, est vitale chez Staphylococcus aureus mais non essentielle chez les bactéries modèles Bacillus subtilis ou Escherichia coli. Chez B. subtilis, les bactéries délétées du gène yvcK, sont sérieusement affectées dans leur croissance et leur morphologie dans des conditions de croissance gluconéogéniques. Les défauts observés peuvent être compensés par l’ajout de fortes concentrations de magnésium ou par l’inactivation de gènes impliqués dans le métabolisme. Ceci suggère que, les mutants yvcK présentent des altérations au niveau de la paroi bactérienne qui sont probablement dues à un désordre du métabolisme. Le phénotype lié à l’absence d’YvcK est similaire à celui observé chez des souches mutées au niveau de gènes impliqués dans la synthèse du peptidoglycane ou constituant le cytosquelette. La protéine MreB, composant majeur du cytosquelette bactérien, forme une structure hélicoïdale sous la membrane cytoplasmique pour positionner les enzymes de synthèse et la maturation du peptidoglycane. In vivo, la protéine YvcK est également localisée sous la forme d’une hélice. Par ailleurs, la surexpression de YvcK supprime le défaut de morphologie du mutant mreB et vice versa. Il a été montré que, chez B. subtilis, la localisation de la protéine membranaire PBP1 était dépendante de MreB. Une délétion de ponA, gène codant pour PBP1, rétablit la viabilité d’un mutant mreB et celle du mutant yvcK dans des conditions de croissance gluconéogéniques. La protéine de fusion GFP-PBP1 dans une souche délétée du gène yvcK, cultivée en milieu liquide CE-gluconate est délocalisée expliquant le gonflement des cellules. Ce résultat suggère que la localisation normale de PBP1 au septum due à la surproduction de YvcK dans un mutant mreB (et réciproquement) permet la restauration de la croissance et de la morphologie. De plus, nous avons montré que, comme son homologue présent chez Mycobacterium tuberculosis, YvcK est phosphorylée in vitro. Nous avons caractérisé la phosphorylation d’YvcK par la protéine kinase PrkC et nous avons identifié la Thr 304 comme site unique de phosphorylation. Cette phosphorylation semblerait jouer un rôle important dans la complémentation du mutant mreB et du repositionnement de la PBP1The YvcK protein is a bacterial conserved protein of unknown function. It is essential in Staphylococcus aureus but not essential in both Bacillus subtilis and Escherichia coli. In B. subtilis, inactivation of the yvcK gene seriously affects growth and morphology on neoglucogenic carbon sources. The defects observed in a yvcK mutant can be offset by the addition of high concentrations of magnesium or by inactivation of genes involved in metabolism. This suggests that, when grown on some carbon sources, yvcK mutants display alterations in their cell wall probably due to a disorder in this metabolism. The phenotype associated with the absence of YvcK is similar to that observed with strains mutated in genes involved in peptidoglycan synthesis or encoding proteins of the cytoskeleton. The major component of cytoskeleton, MreB, an actin-like protein, together with other proteins, forms a helical structure at the cell membrane that participates in the organization and positioning of the enzymes of peptidoglycan synthesis and maturation. We showed that YvcK is organized as a helical like pattern localized near the inner surface of the membrane, independently of the presence of MreB. Surprisingly and despite that these two proteins do not harbour any similarity of sequence or structure, an overproduction of YvcK restored a normal morphology in an mreB mutant strain and vice versa. Furthermore, as already observed for the mreB mutant, in a yvcK mutant strain, the penicillin-binding protein PBP1 is delocalized and deletion of its gene restores growth of a yvcK mutant on gluconate medium. All these results suggest that YvcK is not only involved in the synthesis of cell wall from gluconeogenic carbon sources but also plays a role in cell morphogenesis. In addition, we have shown that similarily to its Mycobacterium tuberculosis homolog, YvcK is phosphorylated in vitro. We have characterized the phosphorylation of YvcK by the protein kinase PrkC and we identified the Thr 304 as the single phosphorylation site. Furthermore, this phosphorylation appears to play an important role in the complementation of the mreB mutant and repositioning of PBP1
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Paraboschi, E. M. "ROLE OF THE PRKCA GENE AND OF MICRORNAS IN THE SUSCEPTIBILITY TO MULTIPLE SCLEROSIS." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/168392.
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Multiple sclerosis (MS) is a multifactorial neurological disorder characterized by chronic inflammation, demyelination, and axonal damage, probably caused by an altered immune response against myelin antigens. Despite extensive studies, the genetic and environmental determinants of MS are still poorly understood. In this thesis, we analyzed the role of the PRKCA gene that encodes the protein kinase C alpha, and has been involved in MS both by linkage and association studies in different populations (Finns, Canadians, and UK population), as well as the possible involvement of microRNAs (miRNAs) in the pathogenesis of MS.
As far as PRKCA is concerned, a case-control association study performed on the Italian population allowed us to identify two association signals in the PRKCA gene: a protective allele mapping in the promoter region (P=0.033; OR=0.12, 95% CI=0.015-0.94) and a risk haplotype, partially overlapping the predisposing haplotypes observed both in Finns and Canadians within PRKCA intron 3 (P=7.4*10-4; OR=1.57, 95% CI=1.24-1.99). We identified and characterized, both in vitro and in vivo, the functional variants underlying these association signals, and demonstrated that higher PRKCA expression levels play a protective role towards MS predisposition. Moreover, we describe here for the first time so-far unknown PRKCA transcript isoforms, which are differentially expressed in MS cases and controls, and eventually lead to the synthesis of aberrant proteins, potentially dangerous for the cells. Furthermore, we characterized the MIR634 gene, mapping within the PRKCA locus, and demonstrated its involvement in the regulation of PRKCA expression.
As far as miRNAs are concerned, we monitored the differential expression of several immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, and identified miR-155 as the most upregulated miRNA in MS cases (fold change=3.30; P=0.013). Interestingly, this miRNA was previously reported to be up-regulated also in MS brain lesions. The role of miR-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms mapping in the miR-155 genomic region. A three-SNP haplotype resulted associated with the disease status (P=0.035; OR=1.36, 95% CI=1.05-1.77), suggesting that this locus strongly deserves further investigations.
In conclusion, this thesis work points to a possible role of post-transcriptional regulation mechanisms in the pathogenesis of MS, particularly supporting the uprising hypothesis that in MS a dysregulation of the splicing may play a pivotal role in MS.
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Cibrian-Uhalte, Elena. "Function of the alpha1B1 subunit of Na +, K + ATPase during zebrafish heart development." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2008. http://dx.doi.org/10.18452/15818.
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Die Zebrafischmutation heart and mind (had), welche die alpha1B1-Untereinheit der Na+,K+ ATPase betrifft, verzögert die Streckung des Herzschlauches und führt zu weiteren Entwicklungsanomalien, die an andere Zellpolaritätsmutanten wie nagie oko (nok) und heart and soul (has) erinnern. In dieser Arbeit habe ich die Funktion und Regulation von Had/Na+,K+ ATPase während der Herzmorphogenese des Zebrafisches und seine möglichen Interaktionen mit Has/Prkci und Nok/Mpp5 untersucht. In konnte nachweisen, dass genetische Interaktionen zwischen had und nok in der Aufrechterhaltung von Zonula-Occludens-1-(ZO-1)-positiven Adhäsionsbändern Adhäsionsbändern in myokardialen Zellen während der Herzentwicklung nachweisen. Meine Ergebnisse deuten darauf hin, dass die Interaktion zwischen Nok/Mpp5 und Had/Na+,K+ ATPase zur Aufrechterhaltung der myokardialen ZO-1-Adhäsionsbändern die Funktion der Na-Pumpe erfordert und dass die korrekte Ionengradienten zur Aufrechterhaltung der myokardialen Integrität beiträgt. Meine Ergebnisse zeigen eine Phosphorylierung des N-terminalen Endes von Had/ Na+,K+ ATPase durch PKCs. PKCs wurden bereits mit der Regulation der Na-Pumpen-Funktion durch Phosphorylierung von N-terminalen Resten in Verbindung gebracht. Meine Ergebnisse legen die Möglichkeit nahe, dass dieser Mechanismus im Zebrafisch konserviert ist. Die Analyse der subzelluläre Lokalisation einer Phosphorylierungs-defizienten Form von Had/Na+,K+ ATPase legt nahe, dass während Herzschlauch-elongation die Had/Na+,K+ ATPase-Aktivität an der Zellmembran durch die Phosphorylierung an einer amino-terminalen Amino-säure reguliert wird. Frühere Studien legen nahe, dass die Herzmorphogenese durch direkte Phosphorylierung von Has/Prkci-Zielen gesteuert wird. Die Identifikation von Has/Prkci-Phosphorylierungs-Zielen könnte dazu beitragen, Herzmorphogenese besser zu verstehen. Aus diesem Grund wurde ein chemisch-genetischer Ansatz entwickelt, um direkte Phosphorylierungs-Ziele von Has/Prkci zu identifizieren.The zebrafish heart and mind (had) mutation which disrupts the alpha1B1 subunit of Na+,K+ ATPase causes heart tube elongation defects and other developmental abnormalities that are reminiscent of several epithelial cell polarity mutants including nagie oko (nok) and heart and soul (has). In this work, I investigated the function and regulatory mechanisms of Had/Na+,K+ ATPase during zebrafish cardiac morphogenesis, as well as its´ possible interactions with Has/Prkci and Nok/Mpp5. In this study, I demonstrate genetic interactions between had and nok in maintaining Zonula occludens-1 (ZO-1) positive junction belts within myocardial cells during heart development. My results strongly suggest that the interaction between Nok/Mpp5 and Had/Na+,K+ ATPase in the maintenance of myocardial ZO-1 junction belts requires the Na pump function and that the correct ionic balance contributes to the maintenance of myocardial integrity. My results show phosphorylation of the N-terminal intracellular tail of Had/Na+,K+ ATPase by PKCs. PKCs have previously been implicated in the regulation of the Na pump function via phosphorylation of N-terminal residues. Therefore, my results raise the possibility that this mechanism is conserved in the zebrafish embryo. The analysis of the subcellular distribution of a phosphorylation-deficient form of Had/Na+,K+ ATPase suggests that, during heart tube elongation, Had/Na+,K+ ATPase activity is regulated at the membrane via phosphorylation at an amino-terminal site. Previous studies suggest that heart morphogenesis is driven via direct phosphorylation of Has/Prkci targets. Therefore, identification of Has/Prkci phosphorylation targets would contribute to better understand cardiac morphogenesis. For this purpose, a chemical genetic approach was designed to identify Has/Prcki direct phosphorylation targets.
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Cuenot, Elodie. "Rôle des Sérine/Thréonine kinases PrkC et CD2148 dans la physiologie du pathogène Clostridium difficile." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC286.
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C. difficile (CD) est un bacille à gram-positif anaérobie strict et sporulant. Ce pathogène est la principale cause d’infections nosocomiales intestinales après une antibiothérapie. La contamination des patients s’effectue via l’ingestion de spores de CD. Suite à une prise d’antibiotiques, une dysbiose du microbiote conduit à des changements dans les pools de métabolites favorisant la germination des spores et la croissance de CD dans le tube digestif. CD va alors produire deux toxines entrainant des dommages cellulaires et une forte inflammation ce qui va conduire à des diarrhées ou des colites pseudomembraneuses. Une partie des cellules de CD va aussi former des spores conduisant à la transmission de l’infection. Lors de son cycle infectieux, CD doit s’adapter rapidement aux changements dans son environnement via la régulation de ses différents processus physiologiques. La phosphorylation est une modification post-traductionnelle réversible. Elle est très souvent utilisée pour moduler l’activité de protéines impliquées dans des voies de signalisation. Les Ser/Thr kinases (STKs) bactériennes phosphorylent leurs substrats sur des résidus Ser ou Thr et régulent de nombreux processus tels que la traduction, le métabolisme du carbone, la synthèse de l’enveloppe, la résistance aux antibiotiques, la division cellulaire ou la virulence. De manière intéressante, CD possède deux STKs, PrkC et CD2148, qui n’ont jamais été étudiées. Ces deux STKs possèdent un domaine kinase cytoplasmique ainsi qu’un segment transmembranaire. Seule PrkC présente une partie extracellulaire composée de 2 domaines PASTA. L’inactivation de PrkC affecte la morphologie ainsi que la division cellulaire de CD. Les cellules du mutant ∆prkC sont hétérogènes en taille. Certaines cellules très allongées ne possèdent pas de septum, d’autres cellules ont un septum mal localisé ou plusieurs septa rapprochés pour environ 15% des cellules du mutant ∆prkC comme observé en microscopie électronique. Nos résultats ont montré que le mutant ∆prkC était capable de sporuler et de germer de manière similaire à la souche sauvage mais présente cependant une motilité réduite ainsi qu’une plus grande capacité à former des biofilms. De plus, le mutant ∆prkC montre une plus grande sensibilité aux céphalosporines qui sont des antibiotiques qui favorisent les infections à CD, à certains peptides antimicrobiens et au lysozyme qui sont l’une des premières lignes de défense de l’hôte et aux sels biliaires secondaires tels que le déoxycholate qui sont toxiques pour les cellules végétatives. En outre, la sensibilité accrue du mutant ∆prkC à ces stress d’enveloppe que CD rencontre dans l’intestin lors du cycle infectieux, pourrait être la cause du délai de colonisation observé pour ce mutant chez le hamster. L’inactivation de PrkC affecte donc l’homéostasie de l’enveloppe de CD. Nous avons montré que la composition du peptidoglycane n’est pas différente entre la souche sauvage et le mutant ∆prkC. En revanche, nous avons mis en évidence un relargage plus important du glycopolymère de surface, le PSII, dans le milieu de culture du mutant ∆prkC. Des résultats préliminaires suggèrent que cet acide téichoïque est également plus présent à la surface du mutant ∆prkC et nous réalisons actuellement des expériences complémentaires pour le vérifier. La structure du PSII étant la même chez les deux souches, ces résultats suggèrent que PrkC est impliquée dans les mécanismes de contrôle de la synthèse du PSII, de son exportation ou de son ancrage au peptidoglycane de CD. Au cours de ce travail, nous avons également commencé l’analyse du mutant CD2148::erm. Les premiers phénotypes observés pour ce mutant sont nettement différents de ceux de ∆prkC puisque l’inactivation de CD2148 affecte le processus de sporulation et la séparation des cellules après division cellulaireClostridium difficile (CD) is the leading cause of intestinal nosocomial post-antibiotic infections in adults. Exposure to certain antibiotics including cephalosporins induces dysbiosis promoting CD infection. Resistance of CD to these antibiotics is a major concern while resistance mechanisms remain poorly characterized. CD produces two toxins that cause epithelial cell damage and inflammation while additional factors associated to cell surface participate in the colonization process. During infection, CD also encounters several stresses in the gut such as secondary bile salts that are toxic for vegetative cells, antibiotics, antimicrobial peptides released by the host, reactive oxygen and nitrogen species produced during inflammation. Pathogen survival depends on its capacity to rapidly adapt to the host environment. Protein phosphorylation is a reversible post-translational modification employed for signal transduction and regulation. Bacterial Ser/Thr kinases (STKs) regulate numerous physiological processes. In response to specific stimuli, STKs phosphorylate substrates on Ser or Thr residues to trigger the appropriate cellular response. Nothing is known about the role of the two STKs of CD, PrkC and CD2148, in the physiology of this enteropathogen. To investigate their function, we constructed ∆prkC and ∆CD2148 mutants. Cells of the ∆prkC mutant had an increased size and abnormal septa. The ∆prkC mutant also had a reduced motility and formed more biofilms. PrkC inactivation increased sensitivity to antimicrobial compounds that CD may encounter in the gut during infection such as deoxycholate, cephalosporins, cationic antimicrobial peptides and lysozyme. This increased susceptibility was not associated to differences in the structure of peptidoglycan. By contrast, we showed that the ∆prkC mutant released more polysaccharide II (PSII) in the supernatant suggesting a decreased deposition of this glycopolymer to the cell surface in this mutant. Our results also revealed that the ∆prkC mutant had a delay in gut implantation in a hamster model. Finally, we observed that the mutant ∆CD2148 formed chains of cells and sporulated more rapidly than the wild-type strain. Accordingly, key sporulation genes were up-regulated in this mutant. Work is now in progress to detect proteins phosphorylated in vivo using phosphoproteomic approaches and to identify substrates of PrkC and CD2148
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Yao, Sheng. "SiRNA inhibition of PRKC-σ-vb expression abrogates the aggressive phenotype of human prostate cancer cells." Thesis, University of Liverpool, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510949.
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The work performed in this Thesis was aimed to elucidate a possible function of PKC~ in human prostate cancer cell-lines. In particular, the role of gene P RKC-(-vb, the predominat isoform expressed in these cells, playing in human prostate tumorigenesis and metastasis, was investigated. The Introduction gIves general information about prostate cancer, PKCs families, particularly PKC-~ and its role in prostate cancer. The Thesis includes six main chapters, presenting data as follows: The gene expression of PRKC-( (PRKC-(-vb, PRKC-(-vn) was determined in prostate malignant and non-malignant cell-lines. Overexpression of both variants of PRKC-(was detected in prostate cancer when compared to non-malignant cell-lines, indicating P RKC-( to be a potential biomarker of prostate cancer. Overexpression of P RKC-l was also detetected in prostate cancer in comparison to non-malignant cell-lines. This result indicated these two PKCs may play similar functions in prostate cancer through phosphorylation of different substrates. To further determine the function of PRKC-(-vb in prostate cancer, gene knockdown cell-lines PRKC-(-vb-Tl-6 and PRKC-(-vb-Tl-2 were established using vector-based RNAi. Reduced gene expression of PRKC-(-vb was confirmed in these two cell-lines when compared to PC3-M parental and scrambles control cell-lines. The transfected cell-lines PRKC-(-vb-Tl-6 and PRKC-(-vb-Tl-2 were further investigated by in-vitro and in-vivo assays. Altered morphology indicated the changed phenotype of the transfectant cells. Reduced proliferation, invasion and anchor-independent growth in transfectant cells indicated reduced malignancy and then suggested the role of PRKC-(-vb in promoting prostate cancer tumorigenesis and metastasis. Reduced tumorigenesis in gene knockdown cells was confirmed by in-vivo assays. Thereafter, potential oncogenic signalling pathways in the gene knockdown cells were investigated by oligonucleotide based micro array. A down-regulated canonical NF-Kl3 pathway was identified in the gene knockdown cell-lines. Moreover, several molecules involved in prostate cancer were detected, indicating that crosstalk of these molecules may exist in prostate cancer. In previously work, a novel sequence was detected to be expressed as extention of 5' primer of "vn". Based on expressed sequences, up-and down-stream of "vn" were determined using RT-PCR. An expressed sequence was detected as an extention of 3' down stream of "vn". However, the method need to be revised to detect the 5' up-stream sequence because Alu blocks were identified at 5' up stream "vn" within 1500bp disturbing further sequencing. Based on the original sequence confirmed previously, a new monoclonal antibody was generated according to the epitope that is different to that of PKC-s. A novel protein specific to prostate cancer was also detected, indicating that a new potential splice variant of PKC-s may be present in prostate cancer. In conclusion, the current study suggests the original hypothesis that expression of P RKC-( is not only a biomarker of prostate cancer but that it plays an important role in promoting prostate cancer tumorigenesis and enhancing tumour metastasis
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Madec, Edwige. "Analyse moléculaire d'une protéine-kinase, PrkC, et d'une phosphatase, PrpC, impliquées dans deux processus de développement chez Bacillus subtilis." Paris 11, 2002. http://www.theses.fr/2002PA112283.
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La phosphorylation des protéines sur les résidus Ser/Thr/Tyr est d'une importance vitale dans de nombreux processus cellulaires. Mes travaux de thèse concernent la caractérisation, pour la première fois de PrkC, une Ser/Thr protéine-kinase de type eucaryote chez Bacillus subtilis. PrkC est une protéine membranaire dont l'organisation topologique est similaire à celle des récepteurs à activité kinase chez l'homme, avec un domaine extracellulaire, présumé senseur, un domaine transmembranaire unique (TMD) et un domaine kinase conservé. Grâce à l'utilisation d'un système génétique, j'ai montré que PrkC forme des dimères, le TMD et le domaine extracellulaire étant capables de promouvoir la dimérisation. En présence d'ATP, la protéine PrkC purifiée, est capable de s'autophosphoryler et de phosphoryler la protéine exogène MBP. Dans les deux cas, la phosphorylation concerne un ou plusieurs résidus thréonine. En collaboration avec Ole Jensen (Danemark), nous avons pu identifier après analyse par spectrométrie de masse en mode tandem MS/MS, huit résidus phosphorylés chez PrkC. Ainsi, quatre Thr sont localisées dans la boucle d'activation, trois Thr dans la région jouxtant la membrane et une Ser dans une région non conservée. La mutagénèse dirigée de ces résidus a montré que l'autophosphorylation de la Ser et des thréonines dans la boucle d'activation est essentielle pour l'activité kinase de PrkC. Parallèlement à ce travail, PrpC, une protéine homologue de la phosphatase humaine PP2C, a été caractérisée. La forme autophosphorylée de PrkC est déphosphorylée par PrpC. Le fait que PrkC et PrpC soient codées par deux gènes adjacents sur le chromosome et cotranscrits, suggère que ces enzymes pourraient fonctionner in vivo comme un couple kinase/phosphatase. La délétion des gènes prkC ou prpC réduit l'efficacité de la sporulation et la formation de biofilms. Une meilleure compréhension du rôle de PrkC et PrpC dans la cellule exige l'identification de leurs cibles/partenairesProtein phosphorylation on Ser/Thr/Tyr residues plays a vital role in many cellular processes. My studies in this Thesis concerned the characterization, for the first time of PrkC, a membrane linked protein kinase in Bacillus subtilis, belonging to the super-family of Hanks kinases, predominantly found in eukaryotes. PrkC was shown to be an integral membrane protein with the topology of some receptor kinases found in humans, with an external domain presumed sensor, a single transmembrane domain (TMD) and a highly conserved kinase domain. I have shown that PrkC forms dimers with both the extracellular domain and the TMD capable of promoting dimerization. In the presence of ATP, PrkC or its catalytic domain, PrkCc, autophosphorylates in vitro and phosphorylates MBP. In both cases, phosphorylation involves one or more Thr residues. In collaboration with Ole Jensen (Danemark), we were able to identify precisely eight phosphorylated residues in PrkC by mass spectrometry. These residues were localised to specific regions of a 3D structure of PrkCc modelled on known kinase structures. Four Thr were localised to the activation loop whereas three Thr are in the juxtamembrane region, and one Ser in a non conserved region. Site directed mutagenesis of these residues confirmed that autophosphorylation of Ser214 and the threonine residues in the activation loop is essential for kinase activity. In a complementary approach, PrpC, a protein phosphatase homologue of the human PP2C family was also characterized. The autophosphorylated form of PrkC was dephosphorylated by PrpC. PrkC and PrpC are encoded by adjacent genes which are co-transcribed. These results indicate that these enzymes form a functional protein kinase/phosphatase couple. Moreover, other studies showed that mutants deleted for prkC or prpC displayed reduced biofilm formation and sporulation frequencies. A better understanding of the role of PrkC and PrpC in the cell requires identification of targets/partners
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Absalon, Cédric. "Identification des cibles du couple Prkc/Prpc et analyse du rôle de la GTPase associée CPGA chez Bacillus subtilis." Paris 11, 2007. http://www.theses.fr/2007PA112171.
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Mes études ont concerné un système de signalisation de fonction inconnue, composé d’une kinase senseur de type eucaryote, d’une phosphatase et d’une GTPase, codées par un groupe de gènes, conservé chez un grand nombre de bactéries à Gram +. Nous avons fait l’hypothèse que PrkC, PrpC et CpgA constitue une voie unique de signalisation liée à la biogénèse de la paroi cellulaire – présence d’un domaine externe PASTA dans PrkC. Ceci s’appuie sur l’implication de CpgA dans la production de peptidoglycane (PG). Ainsi, les cellules déplétées pour CpgA présentent des formes anormales, un dépôt non uniforme de la paroi et l’accumulation de précurseurs tardifs du PG. Une part majeure de mes travaux a porté sur l’identification des cibles de PrkC et PrpC. Tout d’abord, j’ai démontré que CpgA est un substrat de PrkC et de PrpC in vitro, apportant ainsi un argument solide à la relation fonctionnelle des trois protéines. La structure cristalline de CpgA suggérait fortement son rôle comme facteur de traduction. Nous avons donc proposé que CpgA contrôle la synthèse de protéines, capable de coordoner l’expansion de la couche de PG à la synthèse des protéines. Cette hypothèse s’appuie sur ma démonstration que EF-Tu est aussi une cible de PrkC et PrpC. Enfin, j’ai pu identifier une troisième cible de PrkC/PrpC, in vitro et in vivo, YezB, une protéine de fonction inconnue. YezB est un composant du stressosome, connu pour transduire les signaux qui émanent de stress environnementaux, impliqué dans la réponse au stress général, en activant le régulon dépendant de sigma B. La fonction de YezB pourrait être de transduire l’expansion inappropriée du peptidoglycane ou son endommagement, via la phosphorylation par PrkCMy studies have concerned a signalling system of unknown function composed of a eukaryote-like sensor kinase, a phosphatase and a GTPase, encoded by a gene cluster, conserved in many Gram positive bacteria. We hypothesised that PrkC PrpC and CpgA constitute a single signalling pathway concerned cell wall biogenesis – the external PASTA domain of PrkC binds penicillin or peptidoglycan (PG). This was supported by my demonstration that CpgA is implicated in the biogenesis of PG. Thus, cells depleted for CpgA displayed bizarre shapes, non-uniform deposition of the cell wall and accumulation of late PG precursors. A major part of my work also involved identification of targets of PrkC and PrpC. First, the co-ordinated function of the 3 proteins was supported by demonstrating that CpgA is a substrate for PrkC and PrpC in vitro. The crystal structure of CpgA previously indicated a role as a translation factor. Thus we proposed that CpgA controls the synthesis of proteins, including morphogenic factors, or factors coupling the expansion of the PG layer with protein synthesis. This hypothesis is supported by my demonstration that EF-Tu is also a target for PrkC and PrpC. The third target of PrkC/PrpC identified was YezB, a protein of unknown function. YezB is apparently a component of the stressosome that is known to transduce signals, emanating from environmental stress or energy limitation, to activate the sigma B dependent general stress regulon. YezB could conceivably function as a transducer of inappropriate expansion of or damage to the peptidoglycan, via phosphorylation by PrkC
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Landendinger, Melanie [Verfasser]. "Häufigkeit der Spinocerebellären Ataxie Typ 14 (SCA14) in einem Kollektiv von Ataxie-Patienten : Mutationsscreening des Proteinkinase C Gamma-Gens (PRKCG) / Melanie Landendinger." Gießen : Universitätsbibliothek, 2012. http://d-nb.info/106395441X/34.
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Baumann, Ursula [Verfasser], Florian [Akademischer Betreuer] [Gutachter] Bassermann, Bernhard [Gutachter] Küster, and Claus [Gutachter] Belka. "The role of the ubiquitin-proteasome system in the pathology and treatment of B-cell lymphoma : Characterization of the PRKCD-FBXO25-HAX1 axis in lymphomagenesis and treatment resistance of B-cell lymphoma / Ursula Baumann ; Gutachter: Bernhard Küster, Claus Belka, Florian Bassermann ; Betreuer: Florian Bassermann." München : Universitätsbibliothek der TU München, 2017. http://d-nb.info/1137010452/34.
Full textBook chapters on the topic "PRKCδ"
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Newton, Alexandra C. "Protein Kinase C (Prkc)." In Encyclopedia of Signaling Molecules, 4216–22. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_101822.
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Newton, Alexandra C. "Protein Kinase C (Prkc)." In Encyclopedia of Signaling Molecules, 1–6. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_101822-1.
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Ahmed, Tahseen, Tuneer Ranjan Mallick, Michael A. Walter, and Moulinath Acharya. "Role of PRKC Apoptosis WT1 Regulator in Ocular Development and Diseases." In Tumor Suppressor Par-4, 255–67. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-80558-6_16.
Full textConference papers on the topic "PRKCδ"
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Forno, E., Q. Yan, E. Herrera-Luis, M. Pino-Yanes, R. Rios, Y. Y. Han, S. Oh, et al. "PRKCH and Severe Asthma Exacerbations in Latino Children." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a7478.
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Goudarzi, Atta, N. Gokgoz, M. Gill, J. S. Wunder, and I. L. Andrulis. "Abstract 4917: PRKCE and other genetic networks in osteosarcoma metastasis." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4917.
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Joseph, S. K., S. Krlshnamurthi, Y. Patel, and V. V. Kakkar. "1,2-DIOCTANOYLGLYCERIOL (diC8) BUT NOT 1-OLEOYL 2-ACETYLGLYCEROL (OAG) INHIBITS AGONIST-INDUCED PLATELET RESPONSES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644506.
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Inhibition of agonist-induced platelet responses by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PrkC), has been reported. We have examined the effects of the diacylglycerol (DG) analogues OAG and diCg, both PrkC activators, as well as PMA on intracellular Ca2+ ([Ca2+]i) mobilisation and 5-hydroxytryptamine (5HT) release induced by thrombin (T), collagen (Coll.) and the thromboxane (Tx) mimetic U46619. All studies were performed using washed human platelets pre-labelled with either quin-2 or [14C]-5HT and maximal concentrations of agonists. Neither diCg or PMA elevated [Ca2+]i above resting levels though both agents induced a small (10-15%) secretory response. In response to 0.2U/ml T or 0.6uM U46619, but not 20μg/ml Coll., [Ca2+]i increased from resting levels of lOOnM to 758±108nM and 712±58nM respectively. Addition of diCg (60μM) or PMA (16nM) 10 sec before or after T or U46619 reduced the control responses by 10-15% and 30-80% respectively. In contrast, [14C]-5HT secretion in response to T and Coll. was unaffected by diCg or PMA and in the case of U46619 was potentiated 1.4-1.6 fold over control levels. With longer pre-incubation times (5 min) [Ca2+]i mobilisation was further reduced and an inhibitory effect (10-40%) on agonist-induced secretion was evident. Unlike diCg or PMA, OAG (63μM) had no significant inhibitory effect on agonist-induced [Ca2+]i mobilisation and [14C]-5HT secretion even with long pre-incubation times (5 min). However, like diCg and PMA, OAG potentiated U46619-induced secretion with a 10 sec incubation though it induced no secretion itself. The inability of OAG to inhibit may be related to its lesser potency as a PrkC activator. Over a 10 sec-5 min period OAG caused significantly less 40Kd protein phosphorylation ( < 2-fold increase in [32P]-labelling), compared to diCg and PMA (4-6-fold increase). Our results suggest that diCg may be a better tool as an activator of PrkC and DG mimic than OAG. Further, the time course of inhibition of agonist-induced [Ca2+]i mobilisation by diCg suggests that this effect may constitute a physiologically relevant phenomenon mediated by DG within a single cycle of agonist-induced events.
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Krishnamurthi, S., S. K. Joseph, and V. V. Kakkar. "EFFECT OF PROTEIN KINASE C (PrkC) ACTIVATORS ON AGONIST-INDUCED ARACHIDONATE RELEASE IN HUMAN PLATELETS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644508.
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We have examined the effect of 1,2 dioctanoylglycerol (diCg) and phorbol 12-myristate 13-acetate (PMA), both activators of PrkC, on arachidonic acid (AA) release induced by thrombin, collagen and the Ca2+ ionophore, ionomycin, and correlated this with the levels of [Ca2+]i in quin 2-loaded platelets. Experiments were carried out using phenidone (200μM, a combined lipoxygenase and cyclooxygenase inhibitor)-treated washed, human platelets pre-labelled with [3H]-AA or quin 2 and, sub-maximal concentrations of thrombin, collagen and ionomycin. Incubation of platelets with diCg (30 or60μM) or PMA (16nM) over a 15 min period, resulted in no significant release of AA or rise in [Ca2+]i levels compared to that in resting platelets. However, thrombin (0.2U/ml) induced a 6-8% release of [3H]-AA as well as a rise in [Ca2+]i equalling 1μM and, addition of diCg (30-60μM) or PMA (16nM) 10 sec-5 min before or 10-20 sec after thrombin, resulted in a significant reduction (20-40%) of both responses. On the other hand, [3H]-AA release in response to collagen (20μg/ml) and ionomycin (6μM) were significantly potentiated by 1.2-1.9 fold and 1.5-3.0 fold over control respectively, by pre-or post-agonist additions of diCg or PMA.As collagen induced no significant rise in [Ca2+]i levels, the differential effects of diCg and PMA on collagen versus thrombin-induced AA release may be related to inhibitory effects on [Ca2+]i mobilisation induced by the latter. Dose-response curves of ionomycin-induced [Ca2+]i mobilisation and AA release revealed that potentiation of the latter by 10 sec pre-incubations of diCg or PMA, only occurred at [Ca2+]i levels> 1μM, with diCg and PMA not affecting the ionomycin-induced rise in [Ca2+]i. The results suggest that the effect of PrkC activators, on agonist-induced AA release, may depend firstly, on whether AA release is dependent on agonist-induced [Ca2+]i mobilisation and secondly, on whether the latter is inhibited by PrkC activation. Thus, the hypothesis regarding a stimulatory role for PrkC in AA release via lipocortin (Touqui et al, Nature 321, pl77, 1986) needs to be re-assessed in the light of these agonist-related mechanistic differences.
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Rehmani, Hina. "Abstract 4856: Suppression of PRKCI gene-amplified ovarian cancer using aptamer-delivered siRNA." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-4856.
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Rehmani, Hina. "Abstract 4856: Suppression of PRKCI gene-amplified ovarian cancer using aptamer-delivered siRNA." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-4856.
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Galanter, Joshua M., Marc Via, Celeste Eng, Kenny Beckman, Jose Rodriguez-Santana, William Rodríguez-Cintrón, Alfonso Torres-Palacios, Rocio Chapela, Pedro Avila, and Esteban Gonzalez-Burchard. "Polymorphisms In The PRKCA Gene Are Weakly Associated With Asthma But Not BMI In Latino Americans." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1323.
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Irie, Hanna Yoko, Jessica H. Byerly, and Elisa R. Port. "Abstract P3-06-14: Inhibition of PRKCQ enhances chemosensitivity of triple negative breast cancer by regulating EMT and Bim." In Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.sabcs19-p3-06-14.
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Irie, HY, and J. Byerly. "Abstract P2-06-07: PRKCQ regulates taxol sensitivity of triple negative breast cancer cells via IL-6/Stat3 signaling." In Abstracts: Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.sabcs15-p2-06-07.
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