Academic literature on the topic 'Tyrosine protein phosphatase non-receptor type 11'
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Journal articles on the topic "Tyrosine protein phosphatase non-receptor type 11"
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Becker, Helen M., Barbara Schnell, Joba M. Arikkat, Markus Schuppler, Martin J. Loessner, Michael Fried, Gerhard Rogler, and Michael Scharl. "Protein Tyrosine Phosphatase Non-Receptor Type 2 Regulates NLRP3 Inflammasome Activation." Gastroenterology 140, no. 5 (May 2011): S—633. http://dx.doi.org/10.1016/s0016-5085(11)62618-8.
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Scharl, Michael, Kacper A. Wojtal, Helen M. Becker, Anne Fischbeck, Joba M. Arikkat, Theresa Pesch, Silvia Kellermeier, et al. "Protein Tyrosine Phosphatase Non-Receptor Type 2 is a Regulator of Authophagosome Function." Gastroenterology 140, no. 5 (May 2011): S—172. http://dx.doi.org/10.1016/s0016-5085(11)60696-3.
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Sahu, Mahadev, Armiya Sultan, and Manas Ranjan Barik. "Molecular docking and high throughput screening of designed potent inhibitor to PTPN11 involved in Peptic Ulcer." South Asian Journal of Experimental Biology 6, no. 4 (December 23, 2016): 124–30. http://dx.doi.org/10.38150/sajeb.6(4).p124-130.
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In the current study we carried out computational drug designing and dock-ing studies on Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). Scaffold selection was based on the functional properties of PTPN11. Leads were identified based on several physiochemical properties and we created our library with those new molecules that were generated based on Lipinski's rule of five. Further, we carried out high throughput screening on 21 molecules from scaffolds selected. Screening of molecules was based on the criterions such as, TOPKAT (toxicity analysis) and ADMET (absorption, distribution, metabolism, elimination) properties. Among the ligands de-signed, only one compound was identified to have premium interaction within the targeted domain. Pharmacophore was generated and analyzed for selected drug candidate. Our results suggest that O-(3-hydroxy-4-methoxyphenyl) S-methyl dithio dicarbonate is a potent drug molecule in terms of physiochemical and docking properties. In conclusion, the identified compound has great potential to inhibit tyrosine-protein phosphatase non-receptor type 11 (PTPN11).
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Kang, J., P. Posner, and C. Sumners. "Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein." American Journal of Physiology-Cell Physiology 267, no. 5 (November 1, 1994): C1389—C1397. http://dx.doi.org/10.1152/ajpcell.1994.267.5.c1389.
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Angiotensin II (ANG II) elicits an ANG II type 2 (AT2) receptor-mediated increase in outward K+ current (IK; delayed rectifier K+ current) in neurons cocultured from rat hypothalamus and brain stem. Here we have shown that the AT2-receptor-mediated stimulation of neuronal IK by ANG II (100 nM) was abolished by pretreatment of cultures with pertussis toxin (PTX; 200 ng/ml) and by intracellular application of an antibody against the inhibitory guanine nucleotide (GTP) binding protein (anti-Gi alpha, 1:200). Antibodies against other GTP binding proteins (anti-Go alpha, 1:50 and 1:200; anti-Gq/11 alpha, 1:200) did not alter the AT2-receptor-mediated stimulation of neuronal IK by ANG II (100 nM). Furthermore, this effect of ANG II (100 nM) was inhibited by the serine/threonine phosphatase inhibitor okadaic acid (1-10 nM) and by anti-type 2A protein phosphatase (PP2A) antibodies but not by the tyrosine phosphatase inhibitor sodium orthovanadate (1 mM). Thus we have identified key components (Gi and PP2A) of the signal transduction pathway that is responsible for the AT2-receptor-mediated stimulation of neuronal K+ currents.
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HEINRICH, Peter C., Iris BEHRMANN, Gerhard MÜLLER-NEWEN, Fred SCHAPER, and Lutz GRAEVE. "Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway1." Biochemical Journal 334, no. 2 (September 1, 1998): 297–314. http://dx.doi.org/10.1042/bj3340297.
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The family of cytokines signalling through the common receptor subunit gp130 comprises interleukin (IL)-6, IL-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1. These so-called IL-6-type cytokines play an important role in the regulation of complex cellular processes such as gene activation, proliferation and differentiation. The current knowledge on the signal-transduction mechanisms of these cytokines from the plasma membrane to the nucleus is reviewed. In particular, we focus on the assembly of receptor complexes after ligand binding, the activation of receptor-associated kinases of the Janus family, and the recruitment and phosphorylation of transcription factors of the STAT family, which dimerize, translocate to the nucleus, and bind to enhancer elements of respective target genes leading to transcriptional activation. The important players in the signalling pathway, namely the cytokines and the receptor components, the Janus kinases Jak1, Jak2 and Tyk2, the signal transducers and activators of transcription STAT1 and STAT3 and the tyrosine phosphatase SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase] are introduced and their structural/functional properties are discussed. Furthermore, we review various mechanisms involved in the termination of the IL-6-type cytokine signalling, namely the action of tyrosine phosphatases, proteasome, Jak kinase inhibitors SOCS (suppressor of cytokine signalling), protein inhibitors of activated STATs (PIAS), and internalization of the cytokine receptors via gp130. Although all IL-6-type cytokines signal through the gp130/Jak/STAT pathway, the comparison of their physiological properties shows that they elicit not only similar, but also distinct, biological responses. This is reflected in the different phenotypes of IL-6-type-cytokine knock-out animals.
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Idrees, Muhammad, Lianguang Xu, Seok-Hwan Song, Myeong-Don Joo, Kyeong-Lim Lee, Tahir Muhammad, Marwa El Sheikh, Tabinda Sidrat, and Il-Keun Kong. "PTPN11 (SHP2) Is Indispensable for Growth Factors and Cytokine Signal Transduction During Bovine Oocyte Maturation and Blastocyst Development." Cells 8, no. 10 (October 18, 2019): 1272. http://dx.doi.org/10.3390/cells8101272.
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This study was aimed to investigate the role of SHP2 (Src-homology-2-containing phosphotyrosine phosphatase) in intricate signaling networks invoked by bovine oocyte to achieve maturation and blastocyst development. PTPN11 (Protein Tyrosine Phosphatase, non-receptor type 11) encoding protein SHP2, a positive transducer of RTKs (Receptor Tyrosine Kinases) and cytokine receptors, can play a significant role in bovine oocyte maturation and embryo development, but this phenomenon has not yet been explored. Here, we used different growth factors, cytokines, selective activator, and a specific inhibitor of SHP2 to ascertain its role in bovine oocyte developmental stages in vitro. We found that SHP2 became activated by growth factors and cytokines treatment and was highly involved in the activation of oocyte maturation and embryo development pathways. Activation of SHP2 triggered MAPK (mitogen-activated protein kinases) and PI3K/AKT (Phosphoinositide 3-kinase/Protein kinase B) signaling cascades, which is not only important for GVBD (germinal vesical breakdown) induction but also for maternal mRNA translation. Inhibition of phosphatase activity of SHP2 with PHPS1 (Phenylhydrazonopyrazolone sulfonate 1) reduced oocytes maturation as well as bovine blastocyst ICM (inner cell mass) volume. Supplementation of LIF (Leukemia Inhibitory Factor) to embryos showed an unconventional direct relation between p-SHP2 and p-STAT3 (Signal transducer and activator of transcription 3) for blastocyst ICM development. Other than growth factors and cytokines, cisplatin was used to activate SHP2. Cisplatin activated SHP2 modulate growth factors effect and combine treatment significantly enhanced quality and rate of developed blastocysts.
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Honda, H., J. Inazawa, J. Nishida, Y. Yazaki, and H. Hirai. "Molecular cloning, characterization, and chromosomal localization of a novel protein-tyrosine phosphatase, HPTP eta." Blood 84, no. 12 (December 15, 1994): 4186–94. http://dx.doi.org/10.1182/blood.v84.12.4186.bloodjournal84124186.
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Protein-tyrosine phosphatases (PTPases) are considered to play an important role in signal transduction. We previously identified partial sequences of three novel PTPases in a human leukemic cell line. F-36P. We describe here cloning, characterization, and chromosomal localization of one of the newly identified PTPases, termed as HPTP eta (human protein-tyrosine phosphatase eta). The deduced amino acid sequence was composed of an extracellular region homologous to fibronectin type III repeats, a transmembrane region, and a cytoplasmic region containing a single PTPase-like domain. Based on its primary structure, this clone belongs to type-III receptor-type PTPases. The PTPase-like domain showed PTPase activity when expressed in Escherichia coli. Antibody against the extracellular region detected a protein of 220 to 250 kD in human hematopoietic cell lines expressing HPTP eta mRNA. The antibody also recognized a protein of approximately the same molecular weight in COS cells transfected with HPTP eta cDNA, indicating that the antibody specifically recognized HPTP eta gene product and that the cloned cDNA contained full-length coding region. The chromosomal localization determined by fluorescence in situ hybridization showed that the HPTP eta gene was located at chromosome 11p11.2 on the short arm of chromosome 11, which is frequently lost or deleted in human carcinomas.
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Scharl, Michael, Kacper A. Wojtal, Helen M. Becker, Anne Fischbeck, Joba M. Arikkat, Theresa Pesch, Silvia Kellermeier, et al. "The Crohn's Disease Associated Variant of the Protein Tyrosine Phosphatase Non-Receptor Type 2 Gene Affects Cellular Responses to Invading Listeria Monocytogenes." Gastroenterology 140, no. 5 (May 2011): S—496. http://dx.doi.org/10.1016/s0016-5085(11)62052-0.
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G, Bhusnure Omprakash. "In-silico exploration of piperine for invent proton pump and protein phosphatase non-receptor Inhibitors in gastric and peptic ulcer." Journal of medical pharmaceutical and allied sciences 11, no. 6 (December 31, 2022): 5334–38. http://dx.doi.org/10.55522/jmpas.v11i6.1865.
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Anti-ulcer medicines that inhibit the H/K-ATPase enzyme by covalently binding to a cysteine residue of proton pump inhibitors. Through the aforementioned processes, tyrosine-protein phosphatase non-receptor type 11 (PTPN11) causes aberrant mitogenic signals and elongated morphological alterations, as well as the growth and progression of peptic ulcer and gastric cancer.Piperine is an antioxidant derived from the Piper Longum herb. Molecular docking studies and virtual screening were used to investigate it as an H/K ATPase and PTPN11 inhibitor. The Molecular Docking examination was conducted using the Pyrx 0.8 version free database, while virtual screening was conducted using Biovia Discovery Studio software.H/K-ATPase and PTPN11 have substantial binding affinity of 7.5 and 8.6 kcal/mol, respectively, according to molecular docking investigations. Piperine's anti-ulcer efficacy appears to be aided by H/K-ATPase and PTPN11 binding
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Scharl, Michael, Kacper A. Wojtal, Anne Fischbeck, Joba M. Arikkat, Theresa Pesch, Silvia Kellermeier, Stephan R. Vavricka, Michael Fried, Declan F. McCole, and Gerhard Rogler. "The Crohn's Disease Candidate Gene, Protein Tyrosine Phosphatase Non-Receptor Type 2, Regulates Muramyldipetide-Induced NOD2-Dependent Effects in Human Monocytes and Fibroblasts." Gastroenterology 140, no. 5 (May 2011): S—487. http://dx.doi.org/10.1016/s0016-5085(11)62007-6.
Full textDissertations / Theses on the topic "Tyrosine protein phosphatase non-receptor type 11"
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Fourmentraux, Emmanuelle. "Modulation de l'activité lymphocytaire T CD4⁺ par le récepteur inhibiteur KIR2DL1." Paris 7, 2009. http://www.theses.fr/2009PA077022.
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L'activité fonctionnelle des cellules immunes est régulée par un équilibre entre des signaux activateurs et inhibiteurs. Les récepteurs inhibiteurs KIR (Killer cell Ig-like Receptors) exprimés par les cellules NK et par les lymphocytes T effecteurs mémoires lient les molécules du CMH-I et suppriment l'activation cellulaire via le recrutement de SHP-1. Pour mieux comprendre le rôle des KIR sur les cellules T CD4⁺, des transfectants KIR2DL1 ont été obtenus à partir d'une lignée T Jurkat et de lymphocytes T CD4⁺ primaires. Suite à une stimulation du TCR, la production d'IL-2 est augmentée dans les cellules T CD4⁺ transfectées par le KIR2DL1 indépendamment de son engagement, mais suite à son engagement l'activation induite par le TCR est inhibée. La co-stimulation du signal positif initié par le TCR via le KIR2DL1 nécessite des ITIM intacts et fait suite à leur phosphorylation. Il s'en suit le recrutement de SHP-2 et une augmentation de la phosphorylation de PKCθ et ERK. Lors du contact avec une cellule cible, la synapse est caractérisée par une augmentation du recrutement des p-Tyr, de SHP-2 et de la PKCθ. L'interaction avec une cellule cible exprimant les ligands du KIR2DL1 induit sa forte accumulation à la synapse et le recrutement de SHP-1/SHP-2 qui inhibent la production d'IL-2. Le KIR2DL1 induirait deux signaux opposés dans les cellules T CD4⁺ dépendant ou non de son engagement. Les résultats inattendus observés sur la régulation des cellules T CD4⁺ par le KIR2DL1, de part la dualité fonctionnelle des ITIM est fondamentale pour déterminer la capacité du système immunitaire à développer une réponse appropriée, c'est à dire à maintenir la balance tolérance/immunitéThe functional activity of immune cells is controlled by a balance between activators and inhibitors signals. The Inhibitory killer Ig-like receptors (KIR) expressed on NK cells and memory effectors T-cell recognize the CMH-I molecules and inhibit cellular activation by SHP-1 recruitment. To better understand the fonction of KIR receptors on CD4⁺ T-cells, KIR2DL1 transfectants were obtained from human T-cell line and from primary CD4⁺ T-cells. Following TCR stimulation, IL-2 production is increased in CD4+ T cells transfected by KIR2DL1 independently of its engagement. When KIR2DL1 is engaged by its cognate ligand the TCR activation is inhibited. Co-stimulation of the TCR signaling by KIR2DL1 requires intact ITIM and their phosphorylation. It induces a subséquent SHP-2 recruitment and an increased of PKCθ and ERK phosphorylation. Synapses leading to activation are characterized by an increase in the recruitment of p-Tyr, SHP-2, and p-PKCθ. Interaction of KIR2DL1 with its ligand leads to a strong synaptic KIR2DL1 accumulation and SHP-1/SHP-2 recruitment resulting in the inhibition of TCR-induced IL-2 production. These data reveal that KIR2DL1 may induce two opposite signaling outputs in CD4⁺ T cells, depending on whether the KIR receptor is bound to its ligand. The unexpected results observed on the regulation of CD4⁺ T cells by KIR2DL1 receptors, through the functional duality of ITIM, is fundamental to determine the immune System capacity to develop an adapted answer, i. E. To maintain the balance between tolerance and immunity
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Medina-Pérez, Paula Andrea. "Functional characterization of cancer- and RASopathies-associated SHP2 and BRAF mutations." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17420.
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Deregulierung des RAS/MAPK Signalwegs führen nicht nur zur Krebsentstehung, sondern sind auch mitverantwortlich für Entwicklungsstörungen, dieals Keimbahnmutationen in Schlüsselregulatoren des MAPK Signalwegs zurückzuführen sind, werden aufgrund überlappender Phänotypen unter dem Begriff RASopathien subsumiert. Obwohl die Inzidenz für solide Tumore bei diesen Patienten gering ist, wird ein Zusammenhang zum Auftreten verschiedener Leukämieformen deutlich. Im Rahmen dieser Arbeit wurden Mutationen zweier Schlüsselregulatoren des MAPK Signalwegs, PTPN11 und BRAF, hinsichtlich ihrer Fähigkeit zur neoplastischen Transformation analysiert. Zur Durchführung funktioneller Assays wurden Zelllinien mit lentiviraler Vektoren mit NS-, LS- oder NS und Leukämie-assoziierten SHP2 oder CFC-assoz. BRAF Mutationen (Mut), generiert. Die Testung des neoplastischen Potentials erfolgte anhand nicht-tumorigenen humanen sowie an 208F Ratten-Zelllinie. SHP2/BRAF-Mutationen haben eine spindel-ähnliche Zellmorphologie, Proliferation sowie das Dichte- und Anker-unabhängiges Wachstum in 208F gefördert. Diese Ergebnisse sprechen dafür, dass RASopathie-assoziierte Mutationen zu einem Transformationsphänotyp führen können, ähnlich wie die klassischen Ras Onkogenen. Um zu testen, ob Mut-SHP2 das in vivo Tumorwachstum beeinflusst, wurden SHP2-208F-Zellen in Nacktmäuse injiziert. Eine Förderung des Tumorwachstums konnte sowohl durch mut- als auch durch wt-SHP2 beobachtet werden. RASopathie-assoziierte mutierte Proteine führten auch zu einer moderaten Aktivierung des MAPK-Signalwegs. Eine erhöhte Bindungsstärke zu GAB1 konnte mittels ein TAP-Assay ermittelt werden. Auf transkriptioneller Ebene konnte einer Gensignatur, die sowohl durch RASopathien als auch der klassischen onkogenen BRAF identifiziert werden.Die Ergebnisse dieser Studie können für ein besseres Verständnis der Downstream-liegenden Mechanismen von RASopathie-bezogenen Signalwegen und ihrer Beteiligung an der Tumorprogression beitragenDeregulation of the Ras/MAPK signaling is implicated in a variety of human diseases, including cancer and developmental disorders. The RASopathies are characterized by an overlapping phenotype in patients and result from germline mutations in key regulators of the MAPK signaling cascade. Although the incidence of solid tumors is rather low, reports on different leukemia forms have increased. In this work, a group of mutations in the genes PTPN11 and BRAF were selected for expression in cell lines for a comprehensive molecular and phenotypic characterization. Non-tumorigenic human cell lines and the rat 208F fibroblasts were transduced with lentiviral particles with SHP2/BRAF wildtype (wt), Noonan (NS)-, NS- and leukemia- or LS–associated SHP2 mutations (mut) and CFC-associated BRAF mutations to identify their potential roles in neoplastic transformation. Mutations in both genes promoted cell morphology alterations, cell proliferation, density- and anchorage-independent growth in rat fibroblasts. These results suggested that RASopathies-associated mutations in both genes confer a transformation phenotype in vitro similar to the classical oncogenes. To investigate whether mutations in SHP2 contribute to tumor growth in vivo, 208F cells expressing wt/mut SHP2 were injected in nude mice. Both wt/mut SHP2 expressing cells promoted tumor growth. Additionally, RASopathies-associated mutant SHP2 and BRAF proteins constitutively activate the MAPK signaling in a moderate manner compared to oncogenic BRAF. To identify modifications in the protein interaction of mut-SHP2, TAP assays were performed. Mut-SHP2 proteins showed an increased binding strength to GAB1 compared to wt. Finally, a microarray analysis revealed a gene cluster commonly regulated in both RASopathies and the oncogenic BRAF. The findings of this work might be useful for a better understanding of the downstream mechanisms of RASopathies-related signaling and their involvement in cancer progression.
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Hallé, Maxime. "From intracellular localization to proteolytic cleavage : functional significance of protein tyrosine phosphatase PEST regulatory mechanisms." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115683.
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Altered cytoskeletal regulation impacts numerous physiological phenomena: cell motility, apoptosis, oncogenic transformation and parasitic infection. The protein tyrosine phosphatase (PTP)-PEST contains multiple motifs mediating its recruitment to signalling components, and is required for actin filament organization. However, little is known regarding either the importance of PTP-PEST subcellular localization, or the role of PTP-PEST in either parasitic infection or apoptosis. My doctoral research was therefore focussed on elucidating the effect of subcellular distribution on PTP-PEST activity, specifically with respect to regulation of p130Cas (a PTP-PEST substrate), as well as on the involvement of PTP-PEST in both host-pathogen relations and apoptosis. First, PTP-PEST was found both within the cytosol and at the plasma membrane. Using PTP-PEST -/- rescued cell lines, I observed that tyrosine phosphorylation-dependent p130Cas interactions were controlled primarily by cytosolic PTP-PEST. Secondly, infection of fibroblasts with Leishmania major was observed to induce dramatic actin rearrangements, and to alter the phosphorylation state of numerous proteins. Importantly, both PTP-PEST and p130Cas were processed by the parasitic protease GP63 during infection. GP63 was also required for the cleavage of additional host proteins: cortactin, TC-PTP and caspase-3. Of note, Leishmania parasites mediated p38 inactivation, correlating with the proteolysis of its upstream activator TAB1, in a GP63dependent manner. These results indicate that GP63 plays a key role in a number of biochemical events, potentially contributing to Leishmania infectivity. Finally, PTP-PEST was found to relocalize to the edges of retracting membrane ruffles of apoptotic cells. Surprisingly, PTP-PEST was specifically cleaved by caspase-3 at the 549DSPD motif during apoptosis; leading to modification of catalytic activity and scaffolding properties, and sensitizing cells to Fas-mediated detachment. As this data demonstrated a potential role for caspase cleavage in PTP regulation, I also investigated the presence of conserved putative caspase-c1eavage sites in other family members. In summary, the data presented herein links PTP-PEST with various biological processes: oncogenic signalling, host-pathogen interactions, and apoptosis. In addition to demonstrating the involvement of PTP-PEST in diverse signalling pathways, these studies underscore the importance of subcellular localization and proteolysis in the regulation of this PTP.
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Haga, Christopher L. "Analysis of the role of FCRL5 and FIGLERs in B cell development, signaling and malignancy." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008d/haga.pdf.
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Tchankouo, Nguetcheu Stéphane. "Rôle des kinases LAMMER et des phosphatases PTP1B/PTP61F dans la régulation des voies de signalisation médiées par l'insuline." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T067/document.
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Le diabète de type 2 et le cancer représentent des problèmes majeurs de santé publique. Une cible thérapeutique importante de ces affections est la protéine tyrosine phosphatase PTP1B. Cette dernière est connue pour réguler la voie de l’insuline en déphosphorylant le récepteur de l’insuline, IR ou le substrat du récepteur de l’insuline, IRS. Cependant lesfonctions de PTP1B, le mécanisme par lequel cette phosphatase est régulée restent très ou pas connus. Deux études ont notamment décrites des effets opposés de l’activité de PTP1B suite à la phosphorylation sur résidu de Ser50 de PTP1B par CLK1/CLK2, des kinases LAMMER d’une part et AKT d’autre part. AKT a aussi été montré de phosphoryler la kinase LAMMER CLK1. Par ailleurs, le rôle de PTP1B dans la régulation de la voie Ras/MAPK et donc dans le cancer est un sujet très controversé. L’objectif premier de ce travail de thèse a été d’analyser, le rôle de Ptp61F (l’orthologue de Drosophile de PTP1B) dans la voie de l’insuline de Drosophile, l’interaction entre la phosphatase et la kinase LAMMER de Drosophile, DOA, le rôle de cette phosphatase dans la voie RAS/MAPK. Pour se faire, nous avons utilisé la puissance génétique de laDrosophile pour générer un mutant du gène Ptp61F qui a été caractérisé et son rôle dans les voies de signalisation a été étudié. Cette étude a montrée que, Ptp61F interagit avec IR comme PTP1B chez les mammifères. Elle montre que Ptp61F régule les acteurs clés de la voie de l’insuline Pi3K/Akt. Elle a également montrée que Ptp61F pouvait réguler les fonctions du gène de la kinase LAMMER de Drosphile, Doa. Elle montre enfin que Ptp61F interagit avec nombreuses composantes de la voie RASMAPK de Drosophile (Egfr, Ras, rl (ERK humain)) en réprimant la fonction de chacun de ces gènes et que Rl serait un substrat direct de PTP61F. Les informations selon lesquelles, Ptp61F interagit avec Akt et le gène de la kinaseLAMMER de Drosophile, Doa ont été utilisées dans la deuxième étude pour montrer le rôle que les kinases LAMMER (notamment CLK2, Cdc-like kinase 2) pouvaient jouer dans la voie de signalisation de l’insuline au niveau moléculaire en utilisant les cellules de neuroblastome humain SH-SY5Y. Il en ressort que la kinase CLK2 joue un rôle importantdans cette voie de signalisation. CLK2 est induit par l’insuline et son expression augmente avec le temps. PTP1B interagit in vitro et in vivo avec CLK2. La surexpression de CLK2 induit la baisse de la phosphorylation de AKT par un mécanisme qui pourrait passer par PTP1B, puisque in vitro, CLK2 phosphoryle PTP1B et ce dernier interagit avec AKT in vivo. C’est le résidu de Ser50 de PTP1B qui est phosphorylé et cette phoshphorylation réprime l’activité de PTP1B in vitro. On n’observe cependant pas AKT capable de phosphoryler PTP1B in vitro suggérant que la phosphorylation de PTP1B par AKT serait dépendante du contexte cellulaireType 2 diabetes and cancer represent the major public health problems. One important therapeutic target for these pathologies is the protein tyrosin phosphatase PTP1B. The phosphatase is known to negatively regulates the insulin signaling pathway by dephosphorylating the insulin receptor, IR or the insulin receptor substrate, IRS. However,PTP1B functions and its regulation mechanism remain poorly known. Two studies has notably described opposite effects of PTP1B activity following phosphorylation of its Ser50 residue either by CLK1/CLK2, LAMMER kinases or by AKT. Furthermore, AKT, a main insulin signaling pathway component, has been shown to phosphorylate the LAMMER kinaseCLK1 following insulin stimulation. In addition, the role of PTP1B in the regulation of the RAS/MAPK signaling pathway and hence in cancer is a very controversial subject. The first objective of this work was to analyse, the role of Ptp61F (the Drosophila ortholog of human PTP1B) in the Drosophila insulin pathway, the interaction between the phosphatase and the Drosophila LAMMER kinase gene, Doa, the role of Ptp61F in the RAS/MAPK signaling pathway. To achieve these, we took advantage of the genetic powerful of Drosophila to generate a Ptp61F gene mutant which has been characterized and its role in signaling pathways has been studied. This study showed that Ptp61F interacts with IR like PTP1B in mammals. It shows that Ptp61F regulates key components of insulin signaling pathway Pi3K/Akt. It also shows that Ptp61F is able to regulate the Drosophila LAMMER kinase gene, Doa. Finally, we noted that Ptp61F interacts by inhibiting the activity of severalcomponent of the RAS/MAPK signaling pathway of Drosophila (Egfr, Ras, rl (human ERK)) and conclude that Rl coud be a direct substrate of PTP61F. The data showing that Ptp61F interacts with Akt and the Drosophila LAMMER kinase gene, Doa, were the basis for the second study in order to show the role that the mammal LAMMER kinase CLK2 (Cdc-like kinase 2) could play in the insulin signaling pathway at molecular level using the human neuroblastoma cell line SH-SY5Y. From this second study, we show that CLK2 play an important role in insulin signaling. CLK2 is induced by insulin and its expression increases with time. PTP1B interacts in vivo and in vitro with CLK2. Overexpression of CLK2 impairs AKT phosphorylation by a mechanism which could involved PTP1B, since in vitro, CLK2 phosphorylates PTP1B and the latter interacts withAKT in vivo. It is the Ser50 residue of PTP1B being phosphorylated by CLK2 and this phosphorylation event represses PTP1B activity in vitro. AKT cannot phosphorylates PTP1B in vitro, suggesting that the phosphorylation of PTP1B by AKT could be cellular environment dependant
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Santaniemi, M. (Merja). "Genetic and epidemiological studies on the role of adiponectin and PTP1B in the metabolic syndrome." Doctoral thesis, University of Oulu, 2010. http://urn.fi/urn:isbn:9789514261855.
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Abstract The metabolic syndrome is a cluster of components predisposing to type 2 diabetes and cardiovascular disease. Abdominal obesity and insulin resistance seem to be central in the metabolic syndrome, although no unifying pathophysiological mechanism is available. The aim of this thesis was to determine out how the variation in PTP1B and adiponectin gene as well as variations in the plasma adiponectin concentration contribute to the risk of obesity related diseases. PTP1B is a negative regulator of insulin signalling and therefore considered a candidate gene for type 2 diabetes. In the first study, it was found that three PTP1B polymorphisms studied have not strong impact on type 2 diabetes. However, one SNP may be slightly protective against type 2 diabetes, since it was more frequent in the healthy group compared to group of patients with type 2 diabetes. Another SNP was associated with body mass index (BMI). The combination of certain alleles of PTP1B and LEPR (leptin receptor) genes was also associated to BMI. Adiponectin is an adipocytokine expressed in adipose tissue. It has insulin sensitizing effects in liver and muscle and it has also beneficial effects on cardiovascular health. In the second study, the contribution of adiponectin genotypes with obesity-related phenotypes was studied. In Caucasians, the carriers of rare allele of Tyr111His polymorphism were more insulin resistant and at a higher risk of developing type 2 diabetes. In African-Americans, other polymorphisms were associated with BMI and lipids. Thus, the effects of polymorphisms on obesity related phenotypes seemed to be different between ethnic groups. Plasma adiponectin levels were measured from different study groups. In the third study, it was found out that low plasma adiponectin levels associated with different components of the metabolic syndrome and there was a trend towards reductions in adiponectin with an increasing number of components. Fourth study indicated that baseline low adiponectin level associated with a more than 2-fold risk for developing impaired glucose tolerance or type 2 diabetes in the follow-up study of normoglycemic middle-aged Finnish subjects. In the fifth study, plasma adiponectin levels were measured from postmenopausal women receiving estrogen replacement therapy. We observed a reduction in adiponectin levels in women having peroral estradiol which could be part of the "early harm" profile on cardiovascular risk factors of the peroral estrogen replacement therapy detected in clinical trials. These studies further strengthen the role of plasma adiponectin in the obesity related diseases and bring new information of polymorphisms in the adiponectin and PTP1B genes in different populationsTiivistelmä Metabolinen oireyhtymä on kertymä tekijöitä, jotka altistavat tyypin 2 diabetekselle ja sydän- ja verisuonitaudeille. Keskivartalolihavuus ja insuliiniresistenssi, eli insuliinin heikentynyt teho, vaikuttavat olevan keskeisiä metabolisessa oireyhtymässä. Kuitenkaan taustalla olevaa syntymekanismia ei täysin tunneta. Väitöskirjatyön tavoitteena oli tutkia PTP1B- ja adiponektiinigeenin muuntelun sekä plasman adiponektiinitason yhteyttä metaboliseen oireyhtymään, sen osatekijöihin ja seurauksiin. PTP1B on insuliinin toimintaa soluissa estävä molekyyli. Ensimmäisessä tutkimuksessa havaittiin että kolme tutkittua PTP1B-geenin nukleotidimuutosta eivät ole vahvasti yhteydessä tyypin 2 diabetekseen. Eräs nukleotidimuutos saattaisi olla lievästi suojaava tyypin 2 diabetesta vastaan, sillä se oli yleisempi terveillä kuin tyypin 2 diabetesta sairastavilla. PTP1B:n ja leptiinireseptorigeenin eräiden alleelien yhdistelmä oli yhteydessä painoindeksiin. Adiponektiini on rasvakudoksen erittämä hormoni, jolla on suotuisia, insuliinin vaikutusta edesauttavia vaikutuksia elimistössä sekä edullisia vaikutuksia verenkiertoelimistössä. Toisessa työssä havaittiin että Amerikan valkoihoisilla, joilla oli eräs harvinainen adiponektiinigeenin alleeli (Tyr111His), oli heikompi insuliinin teho kuin henkilöillä joilla ei ollut kyseistä muutosta. Tämä alleeli oli yleisempi suomalaisilla tyypin 2 diabetesta sairastavilla kuin terveillä, mikä saattaa tarkoittaa että se liittyy suurentuneeseen riskiin tyypin 2 diabetekselle. Afroamerikkalaisilla taas toiset nukleotidimuutokset olivat yhteydessä lihavuuteen ja plasman rasva-arvoihin. Adiponektiinin pitoisuutta plasmassa mitattiin erilaisissa aineistoissa. Kolmannessa tutkimuksessa havaittiin, että matala pitoisuus oli yhteydessä metabolisen oireyhtymän eri osatekijöihin ja pitoisuus oli sitä matalampi, mitä enemmän osatekijöitä henkilöllä on. Neljännessä tutkimuksessa havaittiin että matala plasman adiponektiinipitoisuus oli yhteydessä suurentuneeseen riskiin saada huonontunut glukoosin sietokyky tai tyypin 2 diabetes tulevaisuudessa. Viidennessä tutkimuksessa adiponektiinitaso määritettiin naisilta jotka olivat ohittaneet vaihdevuodet ja saivat estrogeenikorvaushoitoa. Havaittiin että plasman adiponektiinitaso laski niillä naisilla, jotka saivat korvaushoitoa suun kautta. Tämä saattaisi osittain selittää suun kautta annettavan estrogeenikorvaushoidon epäedullista vaikutusta sydän ja -verisuonitautien riskitekijöihin. Tutkimus vahvistaa edelleen adiponektiinin merkitystä lihavuuteen liittyvissä sairauksissa ja tuo uutta tietoa adiponektiini- ja PTP1B-geenien muuntelun merkityksestä eri väestöissä
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Carmona, Sylvie. "Un analogue de synthèse de la squalamine, NV669, comme nouvel inhibiteur de la protéine Tyrosine Phosphatase 1B (PTP1B) : étude de ses effets in vitro et in vivo sur la croissance des tumeurs pancréatiques et hépatiques." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0616.
Full textAbstract:
NV669 est un aminosterol dérivé de la squalamine qui a montré posséder des propriétés anti-cancéreuses. L'objectif de cette étude a été de rechercher les effets bénéfiques de NV669 sur des modèles de cancers humains pancréatiques et hépatiques et de comprendre les mécanismes cellulaires et moléculaires impliqués dans la diminution de la croissance tumorale par le traitement avec NV669. Les lignées cellulaires humaines pancréatiques (BxPC3 et MiaPaca-2) et hépatiques (HepG2 et Huh7) ont été traitées avec NV669 à différentes concentrations et à différents temps. Les résultats ont montré que NV669 inhibe la prolifération des cellules cancéreuses en induisant l'arrêt du cycle cellulaire en phase G2/M via le complexe cycline B1/Cdk1 et en induisant l'apoptose via le clivage de la caspase-8 et de PARP-1, et la fragmentation de l’ADN.De plus, nos recherches in vitro ont révélé que NV669 inhibe l’activité phosphatase de PTP1B et l’expression de FAK. NV669 affecte l’expression des molécules d’adhérence CDH-1, -2 et -3 dans les lignées BxPC3 et Huh7 qui forment des monocouches cellulaires. Cela suggère qu’en inhibant PTP1B, NV669 induirait l’apoptose.Par la suite, nos résultats in vivo ont montré que NV669 inhibe la croissance des xénogreffes pancréatiques et hépatiques tumorales avec une diminution significative de la prolifération cellulaire et une augmentation de l'apoptose des cellules tumorales. Par conséquent, nos recherches suggèrent que l’analogue de la squalamine, NV669, pourrait être un agent anti cancéreux, utilisé seul ou en association avec d’autres médicaments, dans le traitement de l’adénocarcinome pancréatique et du carcinome hépatocellulaireNV669 is an aminosterol derived from squalamine found to possess strong antiangiogenic and anticancer effects. The aim of this study was to investigate NV669’s beneficial effects on human pancreatic and hepatic cancer models and to understand the cellular and molecular mechanisms involved in tumor growth decrease upon treatment with NV669.Pancreatic (BxPC3, MiaPaCa-2) and hepatic (HepG2, Huh7) cancer cells were treated with NV669, and the effects on proliferation, on cell cycle and death were determined. The results showed that NV669 inhibited the viability of cancer cells, induced cell cycle arrest through the regulation of G2/M phase via a decrease in the expression of cyclin B1 and phosphorylated Cdk1 and the induction of apoptosis via cleaved caspase-8 and PARP-1 and fragmented DNA. Moreover, in vitro NV669 inhibits PTP1B activity and FAK expression. NV669 impacts on the expression of adhesion molecules CDH-1, -2 and -3 in BxPC3 and Huh7 lines that form cell monolayers. This suggests that NV669 by inhibiting PTP1B would induce apoptosis. Subsequently, our in vivo results showed that NV669 inhibited the growth of pancreatic and hepatic tumor xenografts with a significant decrease in proliferation cell and an increase of tumor cell apoptosis. Therefore, NV669 may serve as an alternative anticancer agent, used alone or in association with other medications, for the treatment of pancreatic adenocarcinoma and hepatocellular carcinoma
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Legeay, Samuel. "Physiopathologie de l’endothélium : Applications à l’angiogenèse induite par les répulsifs anti-moustiques à base de DEET et à la dysfonction endothéliale dans le cadre du diabète de type 1 The insect repellent N,N-diethyl-m-toluamide (DEET) induces angiogenesis via allosteric modulation of the M3 muscarinic receptor in endothelial cells." Thesis, Angers, 2016. http://www.theses.fr/2016ANGE0068.
Full textAbstract:
L’endothélium est impliqué dans de nombreux processus physiologiques et physiopathologiques tels que les phénomènes d’inflammation, d’angiogenèse, de prolifération de cellules musculaires lisses et du métabolisme de nombreux médiateurs notamment hormonaux. Ces travaux de thèse avaient pour objectif d’étudier l’endothélium sous deux aspects pouvant conduire à des pathologies : l’angiogenèse et la dysfonction endothéliale. La première étude a permis de mettre en évidence un effet pro-angiogénique in vitro et in vivo du DEET, un répulsif anti-moustiques. Cet effet était associé à une augmentation de la production du monoxyde d’azote (NO),de la phosphorylation de la focal adhesion kinase (FAK) et de l’expression du vascular endothelium growth factor (VEGF) et conduit, in fine, à une augmentation de la croissance tumorale sur un modèle de xénogreffe de tumeur chez la souris. De plus, ces travaux ont montré que l’effet du DEET était engendré au niveau endothélial par une activité inhibitrice sur l’acétyl cholinestérase ainsi que par une modulation allostérique du récepteur muscarinique M3. La deuxième partie consistait à étudier le rôle du stress du réticulum endoplasmique et de la protein-tyrosine phosphatase 1B(PTP1B), une enzyme régulant négativement la voie de l’insuline, dans la dysfonction endothéliale induite par le diabète de type 1 (DT1). Les résultats ont permis d’identifier PTP1B comme une cible potentielle pour le traitement de la dysfonction endothéliale dans le cadre du DT1. L’ensemble de ces travaux de thèse permet une meilleure compréhension de la physiopathologie de l’endothélium et par conséquent fournit des connaissances supplémentaires pour la prise en charge de pathologies impliquant l’endothéliumThe endothelium is involved in plenty physiological and pathophysiological process as inflammation, angiogenesis, smooth muscle cell proliferation and metabolism and catabolism of mediators like hormones.The aim of this work was to study the endothelium from two ways: angiogenesis and endothelial dysfunction. Firstly, we evidenced a pro-angiogenic effect in vitro andin vivo of DEET, a mosquito repellent. This effect was associated with an increase of NO production, focal adhesion kinase (FAK) phosphorylation and vascularendothelial growth factor (VEGF) expression leading to an increase of tumor growth in a mouse-xenograft model. In addition, we showed that the effect of DEET was due to both inhibition of the endothelial acetyl cholinesterase and allosteric modulation of the muscarinic type 3 receptor(M3). Secondly, we studied the role of the endoplasmic reticulum stress and the protein-tyrosine phosphatase 1B(PTP1B) in the type 1 diabetes (T1D)-induced endothelial dysfunction. Results allowed us to identify PTP1B as a potential target for the treatment of the endothelial dysfunction in the context of T1D. All these data supply a better understanding of the pathophysiology of the endothelium and consequently provide additional information for the management of pathologies involving endothelium
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Govind, Nimmisha Harilall. "The role of the protein tyrosine phosphatase non-receptor type 22 gene polymorphism in disease susceptibility and severity in black South Africans with rheumatoid arthritis." Thesis, 2011. http://hdl.handle.net/10539/10841.
Full textAbstract:
BACKGROUND: The protein tyrosine phosphatase non receptor type 22 (PTPN22) gene inhibits T-cell activation. A functional single nucleotide polymorphism (SNP) Arg620Trp (rs2476601), resulting from a C→T substitution at nucleotide position 1858, is a significant risk factor for rheumatoid arthritis (RA) in European populations. The variant allele results in a gain of function that alters the threshold for T-cell signalling and abnormal T regulatory cell function.
AIM: To investigate the role of the PTPN22 R620W polymorphism in disease susceptibility and severity in Black South Africans (BSA) with RA.
METHODS: A cohort of 187 BSA patients with RA and 93 ethnically matched Black and 60 White controls with no history of RA or other autoimmune diseases were studied. Genotyping was performed by the polymerase chain reaction and pyrosequencing.
RESULTS: The rs2476601 SNP was nonpolymorphic in both Black patients and Black control subjects with total absence of the variant ‘T’ allele. In White control subjects the frequency of the ‘T’ allele was 0.092, with T/T, C/T and C/C genotype frequencies of 0.00, 0.183, and 0.817, respectively.
CONCLUSION: This study shows that the rs2476601 SNP of the PTPN22 gene is nonpolymorphic in BSA and therefore not associated with RA but the minor ‘T’ allele frequency in White South Africans is similar to that in other European populations. However, since variations in the rest of the gene were not investigated, these results do not exclude other PTPN22 polymorphisms from playing a role in RA susceptibility in BSA.
Book chapters on the topic "Tyrosine protein phosphatase non-receptor type 11"
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Kotani, Takenori, Yoji Murata, Yasuyuki Saito, and Takashi Matozaki. "Tyrosine-Protein Phosphatase Non-receptor Type 11 (PTPN11)." In Encyclopedia of Signaling Molecules, 1–9. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4614-6438-9_101832-1.
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Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou, et al. "Protein Tyrosine Phosphatase, Non-receptor Type 6 (PTPN6)." In Encyclopedia of Signaling Molecules, 1488. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101107.
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"PTPN (protein tyrosine phosphatase non-receptor type, PTPN22, 1p13)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 1599. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_13802.
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Bin Huraib, Ghaleb, Fahad Al Harthi, Misbahul Arfin, and Abdulrahman Al-Asmari. "The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism and Susceptibility to Autoimmune Diseases." In The Recent Topics in Genetic Polymorphisms. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.90836.
Full textConference papers on the topic "Tyrosine protein phosphatase non-receptor type 11"
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Zhang, Peng, and Zhenghe Wang. "Abstract 229: Identification and functional characterization of p130Cas as a substrate of protein tyrosine phosphatase non-receptor type 14." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-229.
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