Relevant bibliographies by topics / PTPN14

Academic literature on the topic 'PTPN14'

Author: Grafiati
Published: 10 December 2022
Last updated: 28 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Contents

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'PTPN14.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "PTPN14"

1

Hatterschide, Joshua, Amelia E. Bohidar, Miranda Grace, Tara J. Nulton, Hee Won Kim, Brad Windle, Iain M. Morgan, Karl Munger, and Elizabeth A. White. "PTPN14 degradation by high-risk human papillomavirus E7 limits keratinocyte differentiation and contributes to HPV-mediated oncogenesis." Proceedings of the National Academy of Sciences 116, no. 14 (March 20, 2019): 7033–42. http://dx.doi.org/10.1073/pnas.1819534116.

Full text
Abstract:
High-risk human papillomavirus (HPV) E7 proteins enable oncogenic transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate retinoblastoma tumor suppressor (RB1) but cannot degrade PTPN14, we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion ofPTPN14from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to oncogenic transformation, both HPV16 E7-mediated PTPN14 degradation andPTPN14deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV+but not HPV−cancers exhibit a gene-expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated oncogenic activity independent of RB1 inactivation.
APA, Harvard, Vancouver, ISO, and other styles
2

Po’uha, Sela T., Marion Le Grand, Miriam B. Brandl, Andrew J. Gifford, Gregory J. Goodall, Yeesim Khew-Goodall, and Maria Kavallaris. "Stathmin levels alter PTPN14 expression and impact neuroblastoma cell migration." British Journal of Cancer 122, no. 3 (December 6, 2019): 434–44. http://dx.doi.org/10.1038/s41416-019-0669-1.

Full text
Abstract:
Abstract Background Stathmin mediates cell migration and invasion in vitro, and metastasis in vivo. To investigate stathmin’s role on the metastatic process, we performed integrated mRNA–miRNA expression analysis to identify pathways regulated by stathmin. Methods MiRNA and gene arrays followed by miRNA-target-gene integration were performed on stathmin-depleted neuroblastoma cells (CtrlshRNA vs. Stmn Seq2shRNA). The expression of the predicted target PTPN14 was evaluated by RT-qPCR, western blot and immunohistochemistry. Gene-silencing technology was used to assess the role of PTPN14 on proliferation, migration, invasion and signalling pathway. Results Stathmin levels modulated the expression of genes and miRNA in neuroblastoma cells, leading to a deregulation of migration and invasion pathways. Consistent with gene array data, PTPN14 mRNA and protein expression were downregulated in stathmin- depleted neuroblastoma cells and xenografts. In two independent neuroblastoma cells, suppression of PTPN14 expression led to an increase in cell migration and invasion. PTPN14 and stathmin expression did not act in a feedback regulatory loop in PTPN14- depleted cells, suggesting a complex interplay of signalling pathways. The effect of PTPN14 on YAP pathway activation was cell-type dependent. Conclusions Our findings demonstrate that stathmin levels can regulate PTPN14 expression, which can modulate neuroblastoma cell migration and invasion.
APA, Harvard, Vancouver, ISO, and other styles
3

LEHRER, STEVEN, and PETER H. RHEINSTEIN. "PTPN14 Mutations and Cervical Cancer." Cancer Diagnosis & Prognosis 1, no. 4 (September 3, 2021): 275–77. http://dx.doi.org/10.21873/cdp.10035.

Full text
Abstract:
Background/Aim: It was recently shown that rare germline loss-of-function variants in the tyrosine-protein phosphatase non-receptor type 14 (PTPN14) gene conferred substantial risk of basal cell carcinoma (BCC). A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants were associated with high risk of cervical cancer and early age at diagnosis. We used the Cancer Genome Atlas (TCGA) to further evaluate the PTPN14 – cervical cancer association. Materials and Methods: We analyzed the Genomic Data Commons (GDC) TCGA Cervical Cancer (CESC) data set. We used cBioPortal for Cancer Genomics to access data in TCGA. cBioPortal provides visualization, analysis and download options for large-scale cancer genomic data sets. We also accessed TCGA data with the University of California Santa Cruz (UCSC) Xena Browser. UCSC Xena allows users to explore functional genomic data sets for assessing correlations between genomic and/or phenotypic variables. Results: Ten patients with PTPN14 mutations had significantly better survival than 266 patients without PTPN14 mutations (p=0.05 log rank test). In the Human Protein Atlas, low expression of PTPN14 in 85 TCGA cervical cancer specimens was associated with better survival than high expression in 206 cervical cancer specimens. Conclusion: In general, factors that affect the risk of a cancer have the same effect on prognosis. For example, history of allergy reduces risk of malignant brain tumors and improves prognosis. However, this relationship is not the case for PTPN14. We conclude that in TCGA cervical cancer specimens, PTPN14 mutation is a favorable prognostic factor. However, germline variants of PTPN14 confer a worse prognosis. Further studies of the specific mutations would be worthwhile.
APA, Harvard, Vancouver, ISO, and other styles
4

Bottini, Angel, Dennis J. Wu, Rizi Ai, Michelle Le Roux, Beatrix Bartok, Michele Bombardieri, Karen M. Doody, et al. "PTPN14 phosphatase and YAP promote TGFβ signalling in rheumatoid synoviocytes." Annals of the Rheumatic Diseases 78, no. 5 (February 26, 2019): 600–609. http://dx.doi.org/10.1136/annrheumdis-2018-213799.

Full text
Abstract:
ObjectiveWe aimed to understand the role of the tyrosine phosphatase PTPN14—which in cancer cells modulates the Hippo pathway by retaining YAP in the cytosol—in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).MethodsGene/protein expression levels were measured by quantitative PCR and/or Western blotting. Gene knockdown in RA FLS was achieved using antisense oligonucleotides. The interaction between PTPN14 and YAP was assessed by immunoprecipitation. The cellular localisation of YAP and SMAD3 was examined via immunofluorescence. SMAD reporter studies were carried out in HEK293T cells. The RA FLS/cartilage coimplantation and passive K/BxN models were used to examine the role of YAP in arthritis.ResultsRA FLS displayed overexpression of PTPN14 when compared with FLS from patients with osteoarthritis (OA). PTPN14 knockdown in RA FLS impaired TGFβ-dependent expression of MMP13 and potentiation of TNF signalling. In RA FLS, PTPN14 formed a complex with YAP. Expression of PTPN14 or nuclear YAP—but not of a non-YAP-interacting PTPN14 mutant—enhanced SMAD reporter activity. YAP promoted TGFβ-dependent SMAD3 nuclear localisation in RA FLS. Differences in epigenetic marks within Hippo pathway genes, including YAP, were found between RA FLS and OA FLS. Inhibition of YAP reduced RA FLS pathogenic behaviour and ameliorated arthritis severity.ConclusionIn RA FLS, PTPN14 and YAP promote nuclear localisation of SMAD3. YAP enhances a range of RA FLS pathogenic behaviours which, together with epigenetic evidence, points to the Hippo pathway as an important regulator of RA FLS behaviour.
APA, Harvard, Vancouver, ISO, and other styles
5

Fu, Panfeng, Ramaswamy Ramchandran, Mark Shaaya, Longshuang Huang, David L. Ebenezer, Ying Jiang, Yulia Komarova, et al. "Phospholipase D2 restores endothelial barrier function by promoting PTPN14-mediated VE-cadherin dephosphorylation." Journal of Biological Chemistry 295, no. 22 (April 23, 2020): 7669–85. http://dx.doi.org/10.1074/jbc.ra119.011801.

Full text
Abstract:
Increased permeability of vascular lung tissues is a hallmark of acute lung injury and is often caused by edemagenic insults resulting in inflammation. Vascular endothelial (VE)-cadherin undergoes internalization in response to inflammatory stimuli and is recycled at cell adhesion junctions during endothelial barrier re-establishment. Here, we hypothesized that phospholipase D (PLD)-generated phosphatidic acid (PA) signaling regulates VE-cadherin recycling and promotes endothelial barrier recovery by dephosphorylating VE-cadherin. Genetic deletion of PLD2 impaired recovery from protease-activated receptor-1–activating peptide (PAR-1–AP)-induced lung vascular permeability and potentiated inflammation in vivo. In human lung microvascular endothelial cells (HLMVECs), inhibition or deletion of PLD2, but not of PLD1, delayed endothelial barrier recovery after thrombin stimulation. Thrombin stimulation of HLMVECs increased co-localization of PLD2-generated PA and VE-cadherin at cell-cell adhesion junctions. Inhibition of PLD2 activity resulted in prolonged phosphorylation of Tyr-658 in VE-cadherin during the recovery phase 3 h post-thrombin challenge. Immunoprecipitation experiments revealed that after HLMVECs are thrombin stimulated, PLD2, VE-cadherin, and protein-tyrosine phosphatase nonreceptor type 14 (PTPN14), a PLD2-dependent protein-tyrosine phosphatase, strongly associate with each other. PTPN14 depletion delayed VE-cadherin dephosphorylation, reannealing of adherens junctions, and barrier function recovery. PLD2 inhibition attenuated PTPN14 activity and reversed PTPN14-dependent VE-cadherin dephosphorylation after thrombin stimulation. Our findings indicate that PLD2 promotes PTPN14-mediated dephosphorylation of VE-cadherin and that redistribution of VE-cadherin at adherens junctions is essential for recovery of endothelial barrier function after an edemagenic insult.
APA, Harvard, Vancouver, ISO, and other styles
6

Lu, Yingzhi, Zhenxin Wang, Ling Zhou, Zhaoming Ma, Jianguo Zhang, Yan Wu, Yan Shao, and Yunyun Yang. "FAT1 and PTPN14 Regulate the Malignant Progression and Chemotherapy Resistance of Esophageal Cancer through the Hippo Signaling Pathway." Analytical Cellular Pathology 2021 (October 19, 2021): 1–9. http://dx.doi.org/10.1155/2021/9290372.

Full text
Abstract:
Background. Esophageal cancer (EC) is a common malignant tumor, which brings heavy economic burden to patients and society. Therefore, it is important to understand the molecular mechanism of recurrence, metastasis, and drug resistance of esophageal cancer. Methods. Human esophageal cancer cell line TE13 (poorly differentiated squamous cell carcinoma) and normal human esophageal epithelial cell line het-1a were selected for aseptic culture. At the same time, 6 bottles of TE13 cell line were inoculated in logarithmic phase. Cell apoptosis was analyzed by flow cytometry (FCM). Cell clone formation assay was used to analyze the proliferation. Fibronectin-coated dishes were used to detect the characteristics of cell adhesion to extracellular matrix. The Transwell method was used to detect the cell invasion ability. Western blot was used to analyze the expression of Yap1, PTPN14, FAT1, and Myc. Results. Results showed that FAT1 and PTPN14 were downregulated, while Yap1 was upregulated in esophageal cancer tissues. FAT1 inhibited the proliferation, adhesion, and invasion of human esophageal cancer cell lines, which might be associated with the upregulation of PTPN14 and the inhibition of Yap1 and Myc. Conclusion. The results suggested that PTPN14 and FAT1 could regulate malignant progression and chemotherapy resistance of esophageal cancer based on the Hippo signaling pathway.
APA, Harvard, Vancouver, ISO, and other styles
7

Shi, Wenting, and Fang Wang. "circ_AKT3 knockdown suppresses cisplatin resistance in gastric cancer." Open Medicine 17, no. 1 (January 1, 2022): 280–91. http://dx.doi.org/10.1515/med-2021-0355.

Full text
Abstract:
Abstract Background Circular RNAs (circRNAs) are associated with cisplatin resistance in gastric cancer (GC). This study aims to explore the role of circRNA AKT serine/threonine kinase 3 (circ_AKT3) in the resistance of GC to cisplatin. Methods 42 sensitive and 23 resistant GC patients were recruited for tissue collection. The cisplatin-resistant GC cells MKN-7/DDP and HGC-27/DDP were used for in vitro study. circ_AKT3, microRNA-206 (miR-206) and protein tyrosine phosphatase non-receptor type 14 (PTPN14) levels were detected via quantitative reverse transcription real-time PCR (qPCR) and Western blot. Cisplatin resistance was assessed by detecting P-glycoprotein (P-gp) level, half maximal inhibitory concentration (IC50) of cisplatin and cell apoptosis. The target relationship between miR-206 and circ_AKT3 or PTPN14 was analyzed via dual-luciferase reporter and RNA pull-down assays. The role of circ_AKT3 in vivo was assessed using xenograft model. Results circ_AKT3 level was increased, but miR-206 was declined in cisplatin-resistant GC tissues and cells. circ_AKT3 knockdown or miR-206 overexpression decreased the level of P-gp and IC50 of cisplatin and increased apoptosis of MKN-7/DDP and HGC-27/DDP cells. Additionally, circ_AKT3 targeted miR-206, and regulated cisplatin resistance by interacting with miR-206. PTPN14 was regulated by circ_AKT3 through miR-206 as a bridge. Also, circ_AKT3 knockdown decreased xenograft tumor growth. Conclusion circ_AKT3 knockdown suppressed cisplatin resistance using miR-206/PTPN14 axis in cisplatin-resistant GC cells.
APA, Harvard, Vancouver, ISO, and other styles
8

Yoon, Sun-Young, Jinsoo Kim, Bum Soo Lee, Su Cheol Baek, Sang J. Chung, and Ki Hyun Kim. "Terminalin from African Mango (Irvingia gabonensis) Stimulates Glucose Uptake through Inhibition of Protein Tyrosine Phosphatases." Biomolecules 12, no. 2 (February 17, 2022): 321. http://dx.doi.org/10.3390/biom12020321.

Full text
Abstract:
Protein tyrosine phosphatases (PTPs), along with protein tyrosine kinases, control signaling pathways involved in cell growth, metabolism, differentiation, proliferation, and survival. Several PTPs, such as PTPN1, PTPN2, PTPN9, PTPN11, PTPRS, and DUSP9, disrupt insulin signaling and trigger type 2 diabetes, indicating that PTPs are promising drug targets for the treatment or prevention of type 2 diabetes. As part of an ongoing study on the discovery of pharmacologically active bioactive natural products, we conducted a phytochemical investigation of African mango (Irvingia gabonensis) using liquid chromatography–mass spectrometry (LC/MS)-based analysis, which led to the isolation of terminalin as a major component from the extract of the seeds of I. gabonensis. The structure of terminalin was characterized by spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high-resolution (HR) electrospray ionization (ESI) mass spectroscopy. Moreover, terminalin was evaluated for its antidiabetic property; terminalin inhibited the catalytic activity of PTPN1, PTPN9, PTPN11, and PTPRS in vitro and led to a significant increase in glucose uptake in differentiated C2C12 muscle cells, indicating that terminalin exhibits antidiabetic effect through the PTP inhibitory mechanism. These findings suggest that terminalin derived from African mango could be used as a functional food ingredient or pharmaceutical supplement for the prevention of type 2 diabetes.
APA, Harvard, Vancouver, ISO, and other styles
9

Choi, Jaewoo, Anita Saraf, Laurence Florens, Michael P. Washburn, and Luca Busino. "PTPN14 regulates Roquin2 stability by tyrosine dephosphorylation." Cell Cycle 17, no. 18 (September 17, 2018): 2243–55. http://dx.doi.org/10.1080/15384101.2018.1522912.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Wang, W., J. Huang, X. Wang, J. Yuan, X. Li, L. Feng, J. I. Park, and J. Chen. "PTPN14 is required for the density-dependent control of YAP1." Genes & Development 26, no. 17 (September 1, 2012): 1959–71. http://dx.doi.org/10.1101/gad.192955.112.

Full text
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "PTPN14"

1

Hamyeh, Mohamed. "Régulation de l'agressivité tumorale mammaire par la protéine tyrosine phosphatase PTPL1/PTPN13." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT015/document.

Full text
Abstract:
Le cancer du sein est un problème majeur de santé public dont l'incidence est en permanente augmentation. La mortalité est le plus souvent due aux métastases. Les études concernant PTPL1, la plus grande des tyrosines phosphatases cytoplasmiques, ont montré que PTPL1 présente les caractéristiques de suppresseur de tumeur. PTPL1 se trouve mutée dans plusieurs types de cancers et son expression est un marqueur de bon pronostique dans les tumeurs mammaires. Mon laboratoire a également montré que PTPL1 participe à l'effet pro-apoptotique des anti-oestrogènes dans les cellules tumorales hormono dépendantes en déphosphorylant IRSl, le substrat d'IGF1-receptor freinant ainsi la voie PI3K/AKT. PTPL1 régule également la croissance, l'invasion et l'adhésion dans les cellules cancéreuses mammaires peu agressives MCF7.Nous avons établi un modèle cellulaire de clones isogéniques capables d'exprimer PTPL1 ou ses mutants d'une manière inductible dans les cellules cancéreuses mammaires invasives MDA-MB-231. D’une part, nous avons montré un impact négatif de l'expression de PTPL1 sur le phénotype invasif de ces cellules. D'une manière intéressante, le mutant catalytiquement inactif a montré un comportement similaire à celui du contrôle de transfection. Ceci montre l'importance de l'activité catalytique de PTPL1 dans l'inhibition du phénotype agressif. Nous testons maintenant in vivo la tumorigenicité des clones chez les souris athymique.D'autre part, nous avons étudié par protéomique comparative (SILAC) la tyrosine phosphorylation globale des protéines cellulaires dans les cellules MCF-7 et MDA-MB-231 exprimant ou non PTPL1. Parmi les protéines identifiées nous retrouvons des acteurs des différentes voies de signalisations connues dans la littérature pour être impactées par PTPL1 , mais de manière remarquable plus du quart des protéines identifiées sont liées aux jonctions cellulaires ou à leur régulation. Nous avons donc étudié l'effet de la phosphatase sur les jonctions cellulaires et montré que la surexpression de PTPL1 favorise la formation d'agrégats cellulaire en culture 3D, augmente la stabilité des contacts cellulaire en vidéo-microscopie, relocalise la desmogléïne aux jonctions cellulaires et induit une réexpression de la E cadhérine aux niveau du contact cellule/cellule dans les cellules MDA-MB-231.Les jonctions et la polarité cellulaires sont très importantes en cancérologie en particulier dans le processus invasif qui est la première étape de la dissémination métastatique donc il serait maintenant important d'identifier les substrats directs de PTPL1 pour élucider la signalisation de PTPL1 vers les jonctions et proposer de nouvelles cibles thérapeutique
The regulation of breast tumor aggressiveness by Protein Tyrosine Phosphatase PTPL1/ PTPN13Breast cancer is a major problem for public health of which the incidence continues to increase. Its mortality is often linked to metastasis formation. Studies on PTPL1, the largest protein tyrosine phosphatase, have shown that it presents the characteristics of a tumor suppressor gene. PTPL1 is mutated in several types of cancers and its expression is associated with good prognostic in prostate and breast cancers. My team has shown that PTPL1 mediates the pro apoptotic effect of anti-estrogen in hormone-sensitive tumor cells by dephosphorylating IRS1, Insulin growth factor-1 receptor substrate, thus blocking PI3K/Akt pathway. In addition, PTPL1 regulates the growth, the invasion, and the adhesion of low aggressive breast tumor cells MCF-7.Our team established an isogenic cellular model capable of expressing PTPL1 or its mutants (phosphatase-dead and substrate-trapping mutants) in an inducible fashion in invasive cells. We showed that functional PTPL1 expression has a negative impact on cell aggressive phenotypes. Interestingly, the phosphatase-dead mutant exhibits the same behavior as the transfection control. This evidences that PTPL1 activity is crucial for the inhibition of aggressiveness. We are currently testing the clones tumorigenicity in athyemic mice.Furthermore, we conducted a comparative proteomic (SILAC) in order to study the global tyrosine phosphatome in MCF-7 and MDA-MB-231 cells with or without PTPL1. Our findings suggest that PTPL1 regulates the phosphorylation of proteins involved in different signaling pathways already described in the literature to be impacted by PTPL1. Remarkably, the quarter of proteins identified belong to cell junction structure or regulation. We then studied the impact of this phosphatase on cell junctions and showed that PTPL1 overexpression enhances cell aggregate formation in 3D culture, increases cell contact stability, relocates desmoglein to the cell junctions, and induces E-cadherin re-expression at the level of cell-cell contacts in MDA-MB-231 cells.Cell junctions and polarity are very important in oncology and particularly in the invasive process which is the first step in the metastatic dissemination. Our ongoing work focuses on identifying direct substrates for PTPL1 in order to elucidate the underlying PTPL1 signal leading to cell junctions and consequently propose a novel therapeutic targets
APA, Harvard, Vancouver, ISO, and other styles
2

Dromard, Mathilde. "Rôles et mécanismes d'action de la protéine tyrosine phosphatase PTPL1/ptpn13 dans les cancers mammaires et ovariens." Montpellier 2, 2008. http://www.theses.fr/2008MON20040.

Full text
Abstract:
Des études cliniques récentes suggèrent un rôle anti-oncogénique de la Protéine Tyrosine Phosphatase (PTP) PTPL1/ptpn13. L'analyse de l'effet inhibiteur du 4-hydroxytamoxifène (OH-Tam) sur l'action des facteurs de croissance a permis, dans un premier temps, d'identifier le rôle clé joué par une nouvelle classe d'enzymes, les PTPs, et par la suite plus spécifiquement de PTPL1 dans le contrôle de la prolifération cellulaire. Mon travail de thèse a permis de démontrer d'une part, que PTPL1 inhibe l'activation de la voie de signalisation Insulin Receptor Substrate-1 (IRS-1)/PI3K/Akt induite par l'Insulin like Growth Factor 1 (IGF1) au travers de la déphosphorylation d'IRS-1, et que cette PTP est suffisante pour inhiber l'effet d'IGF1 sur la survie cellulaire. D'autre part, nous avons élucidé les mécanismes par lesquels l'anti-œstrogène, OH-Tam, inhibe via PTPL1 la croissance des cellules cancéreuses mammaires induite par le Nerve Growth Factor (NGF). PTPL1 est en effet capable de déphosphoryler le récepteur du NGF, p140TrkA, nécessaire à l'activation des MAPK (Mitogen Activated Protein Kinase) et à la régulation de la croissance cellulaire. Finalement, nous avons mis en évidence un rôle clé de PTPL1 dans l'inhibition de l'invasion, de la mobilité et de la prolifération des cellules cancéreuses ovariennes, ce qui est en accord avec les résultats de notre étude rétrospective montrant un intérêt pronostique du dosage de PTPL1 dans ce type de tumeur. L'ensemble de ces résultats confirme le rôle anti-oncogénique de cette PTP. La mise en évidence des cibles moléculaires de PTPL1 et la compréhension des mécanismes de régulation de son expression, de sa localisation, et de son activité, devraient permettre d'envisager de nouvelles approches thérapeutiques visant à réguler l'expression ou l'activité de cet anti-oncogène
Recent clinical studies have suggested an anti-oncogenic role for the Protein Tyrosine Phosphatase (PTP) PTPL1/ptpn13. Analysis of the inhibitory effect of 4-hydroxytamoxifen (OH-Tam) on growth factor action has allowed to identify the key role played by a new class of enzymes, PTPs, and more specially PTPL1 on the control of cell proliferation. The first part of my PhD studies, has demonstrated that PTPL1 inhibits activation of the Insulin Receptor Substrate-1 (IRS-1)/PI3K/Akt pathway induced by Insulin like Growth Factor 1 (IGF1), through the dephosphorylation of IRS-1, and that PTPL1 is sufficient to inhibit the IGF1 effect on cell survival and to induce apoptosis. Moreover, we have clarified the mechanisms by which the anti-estrogen OH-Tam inhibits Nerve Growth Factor (NGF)-induced breast cancer cells growth through PTPL1. PTPL1 is able to induce dephosphorylation of the NGF receptor, p140TrkA, which is necessary for activation of the MAPK (Mitogen Activated Protein Kinase) pathway and regulation of cell growth. Finally, in agreement with our retrospective studies showing the prognostic value of PTPL1 expression in ovarian tumors, we have also showed an inhibitory effect of PTPL1 on invasion, mobility and proliferation of ovarian cancer cells. Altogether, these results are consistent with the anti-oncogenic role played by this PTP. The identification of PTPL1 molecular targets and our understanding of the mechanisms that regulate its expression, its location and its activities, should allow consideration of new therapeutic approaches to regulate the expression or activity of this anti-oncogene
APA, Harvard, Vancouver, ISO, and other styles
3

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.

Full text
Abstract:
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 cellulaire
Type 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
APA, Harvard, Vancouver, ISO, and other styles
4

Cheyssac, Claire. "Etude de deux gènes candidats du DT2 : EIF4A2 : candidat positionnel au locus 3Q27 et PTPN1/PTP1B : cible pharmacologique dans la sensibilité à l'insuline." Lille 2, 2006. http://www.theses.fr/2006LIL2S009.

Full text
Abstract:
Le diabète de type 2 (DT2) représente la forme la plus commune de diabète touchant plus de 170 millions de personnes dans le monde. Les mécanismes physiopathologiques à l'origine de l'hyperglycémie chronique associent des défauts de sécrétion de l'insuline et de son action sur des organes cibles déterminés par des interactions entre des facteurs de risuqe génétiques et environnementaux. Plusieurs gènes responsables de formes monogéniques de diabète ont été identifiés; toutefois, les déterminants génétiques influençant la prédisposition aux formes communes du DT2 sont encore peu connus. Afin d'identifier de nouveaux variants de susceptibilité, nous avons utilisé deux types d'approches: - une analyse d'association familiale de variants de gènes candidats positionnels au locus 3q27 au sein de familles présentant une liaison génétique avec le DT2 apparaissant avant 45 ans; - et l'exploration d'un gène candidat physiologique , PTPN1, par une étude cas-contrôlés dans plusieurs cohortes de sujets diabétiques et obèses. L'étude du locus 3q27 dans les 148 familles françaises à forte agrégation de DT2 (432 sujets diabétiques et 129 sujets normoglycémiques) a permis de confirmer la liaison génétique ave cl'âge d'apparition du diabète. Deux gènes ont été explorés: KNG1 codant pour kininogène, le précurseur de la bradykinine, et EIF4A2, un facteur d'initiation de la synthèse protéique négativement régulé par le glucose dans des cellules -pancréatiques de rat (INS832/13). Un variant (SNP rs266714 C/T), localisé en amont du gène EIF4A2, a montré une association au DT2 et à l'âge de survenue du diabète au sein des familles. Les paires d'atteints porteuses d'au moins un allèle T à risque montrent un lod-score de 5. 24 pouvant expliquer la liaison au DT2. De plus, ce variant explique en partie la liaison génétique avec l'âge de survenue du diabète. Le SNP rs266714 pourrait modifier le niveau d'expression du facteur EIF4A2 qui module la traduction de certains ARN messagers ainsi que le taux de synthèse protéique notamment dans les cellules -pancréatiques. Le gène PTPN1 code pour la protéine tyrosine phosphatase 1B, régulateur négatif des voies de signalisation de l'insuline et de la leptine. Une association au DT2 et à l'obésité modérée est observée pour un variant au locus du gène PTPN1. Chez 736 sujets normoglycémiques non obèses, 2 SNP introniques sont associés à des variations de traits quantitatifs du métabolisme glucido-lipidique : augmentation du HOMA-B et des triglycérides, diminution du HDL-cholestérol suggérant un rôle possible dans la survenue du syndrome métabolique. Ce type d'approche génétique permet d'améliorer nos connaissances des voies de signalisation pouvant être impliquées dans le développement du DT2 et de proposer de nouvelles cibles thérapeutiques
Type 2 diabetes (T2D) is the most common form of diabetes affecting more than 170 million people worldwide. The T2D pathophysiological mechanisms are characterized by defects of insulin secretion and insulin action leading to chronic hyperglycaemia determined by interactions between genetic and environmental risk factors. Although many genes responsible for monogenic forms of diabetes were identified, genetic determinants influencing T2D predisposition are still largely unknown. To identify new susceptibility variants, we used two approaches : - a familial association study of positional candidate gene variants at the 3q27 locus in falilies showing linkage to T2D with onset before 45 years ; and the exploration of a physiological candidate gene, PTPN1, through case-control analyses in different groups of subjects with type 2 diabetes or obesity. The analysis of the 3q27 locus in French families with strong T2D aggregation (432 diabetes subjects and 129 normoglycaemic subjects) confirmed of a genetic linkage with T2D age-of-onset. Two genes were investigated : KNG1, coding for kininogen, the bradykinin precursor, and EIF4A2 coding for the Eukaryotic Translation Initiation Factor 4 alpha 2, a translation initiation factor involved in protein synthesis which is down-regulated by glucose in rat pancreatic beta cells (INS832/13). A variant (rs266714), located upstream of the EIF4A2 gene showed association with T2D and T2D age-of-onset in the families. Affected sib-pairs sharing at least one at risk T allele showed a LOD-score of 5. 24 which could explain the T2D linkage. Moreover, this variant partly explains the age-of-onset linkage. The rs266714 SNP could modify the expression level of the eIF4A2 factor which modulates mRNA translation and protein synthesis rates in pancreatic beta cells. The PTPN1 gene codes for the protein tyrosine phosphatase 1B, a negative regulator of the insulin and leptin signalling pathways. An association with T2D and moderate obesity is observed for a variant at the PTPN1 gene locus. In 736 normoglycaemic non obese subjects, 2 intronic SNPs associate with variations of quantitative traits of glucose and lipid metabolism : increased HOMA-B and triglycerides, decreased HDL-cholesterol, which suggests a possible role in metabolic syndrome. This genetics approach contributes to an improved understanding of the pathways involved in the development of T2D and to propose new therapeutic targets
APA, Harvard, Vancouver, ISO, and other styles
5

Sanchez-Blanco, Cristina. "Studies of the protein tyrosine phosphatase PTPN22/Lyp in Ptpn22 deficient mice." Thesis, King's College London (University of London), 2015. http://kclpure.kcl.ac.uk/portal/en/theses/studies-of-the-protein-tyrosine-phosphatase-ptpn22lyp-in-ptpn22-deficient-mice(cbcf6c1c-7d57-4df9-95ef-8696a7856858).html.

Full text
Abstract:
An R620W polymorphism in the haematopoietic protein tyrosine phosphatase PTPN22 increases susceptibility to a number of autoimmune diseases, including rheumatoid arthritis. PTPN22 is a negative regulator of immune cell signalling and its role has been best characterised in T cell receptor (TCR) signal transduction. Functional studies in the mouse are needed to clarify the role of Ptpn22 function. In this PhD project, the Ptpn22 deficient mouse was investigated in the context of chronic inflammatory disease, by investigating its role in T cell activation and downstream effector pathways. Ptpn22-/- mice revealed a modest increase in severity of joint inflammation compared to Ptpn22+/+ and Ptpn22+/- mice in a collagen-induced arthritis (CIA) study. Increased proportions of IFN-γ+ CD4+ T cells, CD4+ effector/memory T cells (CD4+ CD44hi CD62Llo) and regulatory CD4+ T cells (CD4+ CD25+ Foxp3+) were observed in Ptpn22-/- mice compared to Ptpn22+/+ littermates in response to immunisation with type II chicken collagen in complete Freund’s adjuvant. This was accompanied by a decrease in the levels of chicken type II collagen specific IgG1:IgG2c, suggesting an enhanced polarisation to the Th1 lineage in the absence of Ptpn22. Ptpn22+/+ and Ptpn22-/- naïve CD4+ T cells polarise to a Th1 phenotype to a similar extent in vitro in the absence of antigen presentation. However, Ptpn22-/- bone marrow derived dendritic cells were found to polarise CD4+ T cells to a Th1 phenotype in in vitro DC: T cell co-culture experiments utilising transgenic OT-II CD4+ T cells. Ptpn22-/- mice developed more severe inflammatory arthritis than Ptpn22+/+ mice in the K/BxN serum transfer arthritis model. The data presented in this thesis describe a negative regulatory role for Ptpn22 in Th1 differentiation in the CIA model resulting in exacerbated inflammatory arthritis in the Ptpn22 deficient mouse. Evidence suggests a T cell extrinsic influence of Ptpn22 deficiency on the antigen presenting cell in promoting pathways of Th1 differentiation. Furthermore, preliminary findings suggest a role for Ptpn22 in the regulation of IgG1 mediated downstream effector pathways. These results highlight a role for Ptpn22 in negatively regulating multiple pathways in the innate and adaptive immune response, alterations in which could ultimately result in autoimmunity.
APA, Harvard, Vancouver, ISO, and other styles
6

Maisonneuve, Pierre. "Etude structurale et fonctionnelle de la phosphatase humaine PTPN4." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066673/document.

Full text
Abstract:
La fonction des protéines de signalisation est déterminée par la nature des domaines qui les composent. Une meilleure compréhension des voies de signalisation passe par l'étude de ces domaines et de leur régulation. PTPN4 est une tyrosine phosphatase qui joue un rôle anti-apoptotique. Lors de l'infection par une souche atténuée du virus de la rage, sa fonction est perturbée, conduisant à la mort des cellules. Cette perturbation est due à l'interaction du motif de reconnaissance au domaine PDZ (PBM) de la glycoprotéine virale avec le domaine PDZ de PTPN4. Nous avons montré que ce domaine PDZ a un rôle d'inhibiteur allostérique de l'activité catalytique de la phosphatase de PTPN4. Ceci représente la première description de la régulation d'une phosphatase par un domaine PDZ. Cette inhibition est levée lors de la fixation d'un ligand au domaine PDZ, tel que le PBM de la glycoprotéine virale. Notre étude structurale révèle que la fixation d'un PBM perturbe les interactions transitoires entre les deux domaines et rétablit ainsi les propriétés catalytiques de la phosphatase. Nous avons par ailleurs identifié un ligand endogène de PTPN4, la MAP Kinase p38 qui, à travers son interaction avec PTPN4, participerait à la régulation de l'homéostasie cellulaire. La formation du complexe implique le recrutement du PBM de p38 par le domaine PDZ de PTPN4. Ainsi, en plus d'avoir une fonction de régulation du domaine phosphatase, le domaine PDZ permet également le recrutement de partenaires et la présentation de substrats au site actif de la phosphatase de PTPN4. Cette étude contribue ainsi à améliorer notre connaissance du rôle des domaines PDZ dans les voies de signalisation cellulaires
The function of signaling proteins is determined by the nature of the domains from which they are made up. A better understanding of cell signaling pathways will result from the study of these domains and their regulation. PTPN4 is a non-receptor tyrosine phosphatase with an anti-apoptotic function. Upon infection with an attenuated rabies virus, its function is hijacked, which subsequently leads to cell death. This phenotype is arises from the interaction of the PDZ binding motif (PBM) of the viral glycoprotein with the PDZ domain of PTPN4. In this study, we show that this PDZ domain is an allosteric inhibitor of the catalytic activity of the PTPN4 phosphatase domain. This is the first description of the regulation of a phosphatase by a PDZ domain. This inhibition is released by the interaction of a ligand to the PDZ domain, such as the viral glycoprotein PBM. Our structural study revealed that the PBM recognition disrupts the transient inter-domain interactions and restores the complete phosphatase catalytic properties. As well, we identified a PTPN4 endogenous ligand, the MAP Kinase p38, which may participate in the regulation of the cellular homeostatic through its interaction with PTPN4. Thus, in addition to its phosphatase regulatory role, the PDZ domain also allows the recruitment of partners and the introduction of substrates to the PTPN4 phosphatase active site. This study contributes to our understanding of the role played by PDZ domains in cell signaling pathways
APA, Harvard, Vancouver, ISO, and other styles
7

Bertola, Débora Romeo. "Estudo do gene PTPN11 nos pacientes afetados pela síndrome de Noonan." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-12042006-110700/.

Full text
Abstract:
INTRODUÇÃO: A síndrome de Noonan é uma doença autossômica dominante caracterizada por baixa estatura, dismorfismos faciais (hipertelorismo ocular, inclinação para baixo das fendas palpebrais, ptose palpebral, palato alto e má-oclusão dentária), pescoço curto e/ou alado, defeitos cardíacos, principalmente a estenose pulmonar valvar, deformidade esternal e criptorquia nos pacientes do sexo masculino. O gene PTPN11, localizado no braço longo do cromossomo 12 (12q24.1), é responsável por aproximadamente 50% dos casos de síndrome de Noonan. OBJETIVO: Detectar a freqüência de mutações no gene PTPN11 em uma amostra de pacientes os quais preenchiam os critérios clínicos para a síndrome de Noonan e síndromes Noonan-like e estabelecer uma correlação genótipo-fenótipo. MÉTODOS: Cinqüenta probandos com síndrome de Noonan, 3 com síndrome de LEOPARD, 3 com síndrome de Noonan-like/lesões múltiplas de células gigantes e 2 com neurofibromatose-Noonan foram incluídos nesse estudo. O estudo molecular foi realizado através da técnica da cromatografia líquida de alta precisão desnaturante e, naqueles com um perfil anormal, a técnica do seqüenciamento do éxon em questão foi concretizada. RESULTADOS: Mutações missense no gene PTPN11 foram identificadas em 21 probandos com síndrome de Noonan (42%), em todos os três pacientes com a síndrome de LEOPARD, em um caso com síndrome de Noonan-like/lesões múltiplas de células gigantes e em um paciente com síndrome da neurofibromatose-Noonan. Este último probando também apresentava uma mutação no gene NF1. A única anomalia que atingiu uma diferença estatisticamente significante quando comparados os grupos de pacientes com e sem mutação foi o grupo de distúrbios hematológicos. Um paciente com síndrome de Noonan que apresentou uma doença mieloproliferativa possuía a mutação T73I. CONCLUSÃO: A síndrome de Noonan é uma doença heterogênea, uma vez que mutações no gene PTPN11 são responsáveis por 42% dos casos. Uma correlação genótipo-fenótipo definitiva não foi estabelecida, mas a mutação T73I parece predispor a distúrbios mieloproliferativos. Com relação às síndromes Noonan-like, o gene PTPN11 é o principal responsável pela síndrome de LEOPARD e também desempenha um papel na síndrome da neurofibromatose-Noonan. A síndrome de Noonan-like/lesões múltiplas de células gigantes, a qual faz parte do espectro da síndrome de Noonan, é também uma doença heterogênea.
INTRODUCTION: Noonan syndrome is an autosomal dominant disorder comprising short stature, facial dysmorphisms (ocular hypertelorism, downslanting palpebral fissures, palpebral ptosis, high arched palate and dental malocclusion), short and/or webbed neck, heart defects, mainly valvar pulmonary stenosis, sternal deformity and cryptorchidism in males. The PTPN11 gene, localized in the long arm of chromosome 12 (12q24.1), is responsible for approximately 50% of the cases. OBJECTIVE: To detect the PTPN11 gene mutation rate in a cohort of clinically well-characterized patients with Noonan and Noonan-like syndromes and to study the genotype-phenotype correlation. METHODS: Fifty probands with Noonan syndrome ascertained according to well-established diagnostic criteria, 3 with LEOPARD syndrome, 3 with Noonan-like/multiple giant cell lesion syndrome and 2 with neurofibromatosis/Noonan were enrolled in this study. Mutational analysis was performed using denaturing high-performance liquid chromatography followed by sequencing of amplicons with an aberrant elution profile. RESULTS: Missense mutations in the PTPN11 gene were identified in 21 probands with Noonan syndrome (42%), in all three patients with LEOPARD syndrome, in one case with Noonan-like/multiple giant cell lesion syndrome and in one with neurofibromatosis-Noonan syndrome. This last patient also showed a NF1 gene mutation. The only anomaly that reached statistical significance when comparing probands with and without mutations was the hematological abnormalities. A Noonan syndrome patient presenting a myeloproliferative disorder showed a T73I mutation. CONCLUSION: Noonan syndrome is a heterogeneous disorder, once PTPN11 gene mutations is responsible for 42% of the cases. A definitive genotype-phenotype correlation is not established, but the T73I mutation seems to predispose to a myeloproliferative disorder. Regarding Noonan-like syndromes, the PTPN11 gene is the main one in LEOPARD syndrome and also plays a role in neurofibromatosis-Noonan syndrome. Noonan-like/multiple giant cell lesion syndrome, part of the spectrum of Noonan syndrome, is also heterogeneous.
APA, Harvard, Vancouver, ISO, and other styles
8

Keren, Boris Verloes Alain. "Syndrome de Noonan et mutations du gène PTPN11 corrélations génotype-phénotype /." Créteil : Université de Paris-Val-de-Marne, 2006. http://doxa.scd.univ-paris12.fr:80/theses/th0247734.pdf.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Chadwick, Michelle. "Characterization of a Novel Mouse Model for Angiosarcoma in Which Combined Inhibition of mTOR and MEK Results in Tumor Suppression." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1490353768809798.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Abdessamad, Mahmoud. "Caractérisation moléculaire et fonctionnelle des signalosomes PTEN/MAGI-1b/TRIP6 et PTEN/PTPN13." Paris 7, 2012. http://www.theses.fr/2012PA077048.

Full text
Abstract:
Le suppresseur de tumeurs PTEN est une phosphatase capable de déphosphoryler certains résidus tyrosine, mais également les phosphoinositides produits de la PI3K. Dans son extrémité C- terminale, PTEN comporte un motif d'interaction avec les domaines PDZ. Notre équipe a établi le rôle majeur de l'activité lipide-phosphatase dans la stabilisation des contacts cellulaires et le contrôle de l'invasion. PTEN est recruté vers les jonctions cellulaires E-cadhérine β-caténine, via la molécule à domaines PDZ MAGI-1. Afin d'identifier de nouveaux partenaires de PTEN, nous avons engagé une approche par le système de double hybrides. Cette approche a permis d'identifier TRIP6 et PTPN13. Nous avons montré que TRIP6 induit l'invasion des cellules épithéliales MDCK, via i) la compétition avec les (3-caténines pour lier MAGI-1 et la déstabilisation des complexes jonctionnels, ii) l'activation des voies de signalisations dépendantes de la PI3K et de NFKB (FASEB J 23:916,2009). PTPN13 est une tyrosine phosphatase qui comporte 5 domaines PDZ. Nous avons confirmé l'interaction de PTEN avec le domaine PDZ2 de PTPN13 in vitro et ex vivo. Nous avons montré que PTEN est substrat de PTPN13 in vitro. De même, la surexpression de PTPN13 native, mais pas d'une forme défective dans l'activité phosphatase, induit une diminution de la phosphorylation de PTEN. Cette surexpression n'affecte pas le niveau de phosphorylation de Akt -reflet de l'activité de cette kinase- dans des lignées déficientes en PTEN, mais potentialise les effets inhibiteurs de PTEN sur cet effecteur de la PI3K. Par conséquent, nos résultats démontrent le rôle critique de PTPN13 dans le contrôle de la signalisation dépendante de PTEN
The PTEN tumor suppressor is a multifunctional protein endowed with a phosphatase activity that dephosphorylates not only some phosphotyrosine residues, but also the phosphoinositides generated by PI3K. In its C-terminus, PTEN encodes a PDZ-binding motif. Our Team has demonstrated the critical role of the lipid phosphatase activity of PTEN in stabilizing junctional complexes and in reverting invasiveness. PTEN interacts with cadherin β3-catenin complexes through the PDZ domain containing- protein MAGI-1. To identify new molecular PTEN partners, we applied yeast-two-hybrid assay, and identified TRIP6 and PTPN13. We have demonstrated that TRIP6 induces invasiveness of the MDCK epithelial cells, through i) the competition with (3-catenin for binding to MAGI-1 b and the destabilization of junctional complexes, ii) the activation of the PI3K/ Akt, and NFKB signaling pathways (FASEB J 23:916,2009). PTPN13 is a tyrosine phosphatase with 5 PDZ domains. We have confirmed the interaction of PTEN C-terminus with the 2nd PDZ domain of PTPN13 in vitro and ex vivo. We showed that PTEN is a PTPN13 substrate in vitro. In line with these results, the overexpression of wild-type PTPN13, but not of a mutant deficient in phosphatase activity decreased PTEN phosphorylation. This overexpression did not alter Akt phosphorylation -a reflect of the activity of this kinase- in PTEN deficient cell lines, but potentiated PTEN effects on this downstream target of PI3K. Thus, our results demonstrated the critical role of PTPN13 in controling PTEN signaling pathway
APA, Harvard, Vancouver, ISO, and other styles
More sources

Books on the topic "PTPN14"

1

Dulczewski, Zygmunt. Archiwum Floriana Znanieckiego PTPN w Poznaniu. Poznań: PTPN, 1999., 1999.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
2

Nurjanah. Kisah sukses mitra binaan PTPN VII. Bandarlampung: Perusahaan Perseroan, PT Perkebunan Nusantara VII, 2010.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
3

Bangun, Mulya. Pers reformasi Indonesia: Tantangan globalisasi BUMN-PTPN abad 21. [Medan]: HPI-PPI Tabloid Primadona, 2000.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
4

Alijoyo, F. Antonius. Leaping to the next curve: Perjalanan PTPN 13 menuju organisasi kelas dunia. Jakarta: Salemba Empat, 2003.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
5

Agustono, Budi. Badan Perjuangan Rakyat Penunggu Indonesia vs PTPN II: Sengketa tanah di Sumatera Utara. Bandung: Diterbitkan untuk Wahana Informasi Masyarakat (WIM) oleh Akatiga, Pusat Analisis Sosial, 1997.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
6

Atikah, Warah. Sengketa tanah perkebunan: Studi kasus tanah kebun Kalibakar PTPN XII (Persero), Kecamatan Dampit, Kabupaten Malang : laporan penelitian. [Jember]: Departemen Pendidikan Nasional RI, Universitas Jember, Lembaga Penelitian, 2003.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
7

Wahyudi. Formasi dan struktur gerakan sosial petani: Studi kasus reklaiming/penjarahan atas tanah PTPN XII (Persero) Kalibakar, Malang Selatan. Malang: UMM Press, 2005.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
8

Eyre, Steve, and Jane Worthington. Genetics of rheumatoid arthritis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0040.

Full text
Abstract:
A range of epidemiological studies have clearly established that susceptibility to rheumatoid arthritis (RA) is determined by both genetic and environmental factors. Studies over the last five decades have used a variety of approaches to identify the genetic variants associated with disease. HLA DRB1 was the first RA susceptibility locus to be discovered and has the largest effect size. We describe current understanding of the complexities of HLA association for RA. Linkage and small-scale association studies prior to 2007 provided convincing evidence for only one more RA susceptibility locus, PTPN22. Major breakthroughs in high-throughput genotyping and systematic discovery and mapping of hundreds of thousands of single nucleotide polymorphisms (SNPs) led to large-scale genome-wide association studies used for the first time for RA in 2007. This approach has had a dramatic impact on our knowledge of the susceptibility loci for RA, such that over 60 risk variants have now been robustly identified. We present an overview of these studies and the loci that have been identified. We consider how this knowledge is contributing to a greater understanding of the aetiology and pathology of the disease and in turn how this can influence management of patients presenting with an inflammatory arthritis. We consider some of the unanswered questions and the approaches that will need to be taken to address them.
APA, Harvard, Vancouver, ISO, and other styles
9

Eyre, Steve, Jane Worthington, and Sebastien Viatte. Genetics of rheumatoid arthritis. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0040_update_003.

Full text
Abstract:
A range of epidemiological studies have clearly established that susceptibility to rheumatoid arthritis (RA) is determined by both genetic and environmental factors. Studies over the last five decades have used a variety of approaches to identify the genetic variants associated with disease. HLA DRB1 was the first RA susceptibility locus to be discovered and has the largest effect size. We describe current understanding of the complexities of HLA association for RA. Linkage and small-scale association studies prior to 2007 provided convincing evidence for only one more RA susceptibility locus, PTPN22. Major breakthroughs in high-throughput genotyping, and systematic discovery and mapping of hundreds of thousands of single nucleotide polymorphisms (SNPs) led to large-scale genome-wide association studies used for the first time for RA in 2007. Widespread utilization of this approach has had a dramatic impact on our knowledge of the susceptibility loci for RA, such that over 100 risk variants have now been robustly identified. We present an overview of these studies and the loci that have been identified. We consider how this knowledge is contributing to a greater understanding of the aetiology and pathology of the disease, and in turn how this can influence management of patients presenting with an inflammatory arthritis. We consider some of the unanswered questions and the approaches that will need to be taken to address them.
APA, Harvard, Vancouver, ISO, and other styles
10

Jerzy, Świdziński, and Poznańskie Towarzystwo Przyjaciół Nauk. Komisja Filologiczna., eds. Z problematyki współczesnych przekładów twórczośći Mickiewicza na języki obce: Materiały ze spotkania tłumaczy Mickiewicza zorganizowanego przez Komisję Filologiczną PTPN w dniu 30 maja 1995 w Śmiełowie. Poznań: Wydawn. Poznańskiego Tow. Przyjaciół Nauk, 1999.

Find full text
APA, Harvard, Vancouver, ISO, and other styles

Book chapters on the topic "PTPN14"

1

Bauler, Timothy J., and Philip D. King. "PTPN3/PTPN4." In Encyclopedia of Signaling Molecules, 4294–98. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_535.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Bauler, Timothy J., and Philip D. King. "PTPN3/PTPN4." In Encyclopedia of Signaling Molecules, 1–4. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_535-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou, et al. "PTPN3/PTPN4." In Encyclopedia of Signaling Molecules, 1509–12. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_535.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Stanford, Stephanie M., Massimo Bottini, and Nunzio Bottini. "PTPN22." In Encyclopedia of Medical Immunology, 931–41. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-0-387-84828-0_46.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Villars, P., K. Cenzual, R. Gladyshevskii, O. Shcherban, V. Dubenskyy, V. Kuprysyuk, I. Savysyuk, and R. Zaremba. "PtPb4." In Landolt-Börnstein - Group III Condensed Matter, 609. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-22847-6_506.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Shio, Marina Tiemi, and Martin Olivier. "PTPN6." In Encyclopedia of Signaling Molecules, 4298–308. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_309.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Shio, Marina Tiemi, and Martin Olivier. "PTPN6." In Encyclopedia of Signaling Molecules, 1–11. New York, NY: Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4614-6438-9_309-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou, et al. "PTPH1." In Encyclopedia of Signaling Molecules, 1509. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101123.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou, et al. "PTPN5." In Encyclopedia of Signaling Molecules, 1512. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101125.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Donato, Dominique M., Steven K. Hanks, Kenneth A. Jacobson, M. P. Suresh Jayasekara, Zhan-Guo Gao, Francesca Deflorian, John Papaconstantinou, et al. "PTPN6." In Encyclopedia of Signaling Molecules, 1512–20. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_309.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "PTPN14"

1

Liu, Xiaojun, Nuo Yang, Sheila A. Figel, Kayla E. Wilson, Carl D. Morrison, Irwin H. Gelman, and Jianmin Zhang. "Abstract LB-520: PTPN14 interacts with and negatively regulates the oncogenic function of YAP." 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-lb-520.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Ružickij, Robert, and Raimondas Grubliauskas. "PADANGŲ TEKSTILĖS PLUOŠTO ATLIEKŲ LYGINAMOJO GARSO SUGERTIES KOEFICIENTO TYRIMAS IR VERTINIMAS." In 25-osios jaunųjų mokslininkų konferencijos „Mokslas – Lietuvos ateitis“ teminės konferencijos APLINKOS APSAUGOS INŽINERIJA. Vilniaus Gedimino Technikos Universitetas, 2022. http://dx.doi.org/10.3846/aainz.2022.010.

Full text
Abstract:
Padangų perdirbimo procesas yra gerai žinomas. Gumos granulės sėkmingai panaudojamos statybos sektoriuje, tačiau padangų tekstilės pluoštas (PTP) išlieka problema, nes nėra žinoma, kur galima panaudoti. Šiame straipsnyje nagrinėjamas PTP atliekų pakartotinis panaudojimas kaip garso sugerties medžiaga. Tyrimo tikslas yra įvertinti PTP garso sugerties efektyvumą, kai medžiagoje yra skirtingas gumos priemaišų kiekis. Tyrimai darbe buvo atlikti esant trims skirtingiems gumos granulių priemaišų kiekiams. Vieninė lyginamoji garso sugerties koeficiento vertė taikoma apibūdinant garsą sugeriančius statybos gaminius, kurie naudojami pastatuose – laiptinėse, laukimo salėse, gamybinėse patalpose ir pan. Rezultatų apibendrinimo metodas paremtas ISO 11654 standartu. Tyrimo rezultatai parodė, kad gu- mos priemaišų padidėjimas PTP atliekose turi neigiamos įtakos garso sugerčiai. Mėginių, kurie turi iki 10 % gumos priemaišų (PTP10), vyraujanti lyginamoji garso sugerties vertė siekė D klasę, kurios reikšmės kito nuo 0,30 iki 0,55. Kai gumos priemaišų kiekis buvo iki 54 % (PTP54), mėginių vyraujančios lyginamosios garso sugerties vertės siekė E ir D klases, kurios atitinkamai kito nuo 0,15 iki 0,25 ir nuo 0,30 iki 0,55. Gumos priemaišų kiekiui padidėjus iki 70 % (PTP70), vyraujanti lyginamoji garso sugerties vertė siekė E klasę, kurios reikšmės kito nuo 0,15 iki 0,25. PTP10 mėginių, turinčių iki 10 % gumos priemaišų, garso sugerties geba yra 31 % didesnė, lyginant su PTP54 mėginiais, ir 35 % didesnė, lyginant su PTP70 mėginiais.
APA, Harvard, Vancouver, ISO, and other styles
3

Quintero, Luis Alberto Perez, and Michel L. Tremblay. "Abstract 1741: Reduced PTPN1/PTPN2 activity synergistically enhanced anti-tumoraleffector functionof CD8 T cells." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1741.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Perez-Quintero, Luis Alberto, Yevgen Zolotarov, Zuzet Martinez-Cardoba, Chu Han Feng, Alexandre Poirier, Kelly Anne Pike, Jean-Sebastien Delisle, and Michel L. Tremblay. "Abstract NG16: Concomitant reduction of PTPN1/PTPN2 activity synergistically enhanced antitumoral effector function of CD8 T cells." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-ng16.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Abdelsalam, Shahenda Salaheldine, and Abdelali Agouni. "Protein Tyrosine Phosphatase (PTP) 1B Inhibition Improves Endoplasmic Reticulum Stress-Induced Apoptosis and Impaired Angiogenic Response in Endothelial Cells." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0110.

Full text
Abstract:
Insulin is not only important for glucose homeostasis, but also plays a critical role in the activation of endothelial nitric oxide synthase (eNOS) to synthesize nitric oxide (NO) and keeping the endothelium functional. Conditions which result in insulin resistance, such as diabetes and obesity, cause impairment of endothelial function, a condition known as endothelial dysfunction that features a reduced release of NO. Protein tyrosine phosphatase (PTP) 1B, is a known negative regulator of insulin receptor, that has been implicated in the pathogenesis of insulin resistance and endothelial dysfunction. Owing to its critical location at the surface of the endoplasmic reticulum (ER), PTP1B has been found to play an important role in ER stress response. However, the role of ER stress in PTP1B-mediated endothelial dysfunction is not fully elucidated. Toa address this, ER stress was induced pharmacologically in endothelial cells using thapsigargin, in the presence or absence of either a small molecule inhibitor of PTP1B or silencing siRNA duplexes, followed by the assessment of the expression of key ER stress markers, angiogenic capacity and apoptotic signals. We report here, that PTP1B inhibition protected cells against ER stress and ER stress-induced impairment in eNOS activation and angiogenic capacity. PTP1B inhibition or silencing also protected against ER stress-induced endothelial cell apoptosis. Moreover, PTP1B blockade also suppressed ER stress-activated autophagy. Our data emphasize on the critical role of PTP1B in ER stress-mediated endothelial cell dysfunction and highlights the therapeutic potential of PTP1B inhibition against ER stress-mediated cell death and impairment of endothelial function to prevent cardiovascular disease in pathologies charactereized by the activation of ER stress such as diabetes.
APA, Harvard, Vancouver, ISO, and other styles
6

Ruess, D., G. Heynen, K. Ciecielski, W. Birchmeier, R. Schmid, and H. Algül. "PO-201 Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase." In Abstracts of the 25th Biennial Congress of the European Association for Cancer Research, Amsterdam, The Netherlands, 30 June – 3 July 2018. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/esmoopen-2018-eacr25.719.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Mainardi, S., A. Mulero-Sánchez, A. Prahallad, G. Germano, A. Bosma, C. Lieftink, E. Nadal, A. Bardelli, A. Villanueva, and R. Bernards. "PO-019 PTPN11 is a therapeutic target in KRAS mutant lung cancer." In Abstracts of the 25th Biennial Congress of the European Association for Cancer Research, Amsterdam, The Netherlands, 30 June – 3 July 2018. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/esmoopen-2018-eacr25.554.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Ghazalpour, A., RP Bender, MJ McGinniss, and R. Ashfaq. "PD08-09: PTPN12 Gene Expression Signature in Triple Negative Breast Cancer Cohort." In Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/0008-5472.sabcs11-pd08-09.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Hill, Kristen Suzanne, Evan Roberts, Ellen Marin, Xue Wang, Jamie Teer, Jane Messina, Jerry Wu, and Minjung Kim. "Abstract 2387: The oncogenic role and therapeutic potential of PTPN11 in melanoma." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2387.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Vermeer, Paola D., Nichole Haag, Kimberly M. Lee, Daniel W. Vermeer, Bryant G. Wieking, and John H. Lee. "Abstract 2114: PTPN13 regulates ephrinB1 reverse signaling, MAP kinase signaling and tumor growth." 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.am2011-2114.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Reports on the topic "PTPN14"

1

Huang, Jiaoti. Function of PTP1B in Neuroendocrine Differentiation of Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, January 2008. http://dx.doi.org/10.21236/ada481731.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Dickman, Martin B., and Oded Yarden. Modulation of the Redox Climate and Phosphatase Signaling in a Necrotroph: an Axis for Inter- and Intra-cellular Communication that Regulates Development and Pathogenicity. United States Department of Agriculture, August 2011. http://dx.doi.org/10.32747/2011.7697112.bard.

Full text
Abstract:
The long-term goals of our research are to understand the regulation of sclerotial development and pathogenicity in S. sclerotiorum. The focus in this project is on the elucidation of the signaling events and environmental cues that contribute to broad pathogenic success of S. sclerotiorum. In this proposal, we have taken advantage of the recent conceptual (ROS/PPs signaling) and technical (genome sequence availability and gene inactivation possibilities) developments to address the following questions, as appear in our research goals stated below, specifically concerning the involvement of REDOX signaling and protein dephosphorylation in the regulation of hyphal/sclerotial development and pathogenicity of S. sclerotiorum. Our stated specific objectives were to progress our understanding of the following questions: (i) Which ROS species affect S. sclerotiorum development and pathogenicity? (ii) In what manner do PPs affect S. sclerotiorum development and pathogenicity? (iii) Are PPs affected by ROS production and does PP activity affect ROS production and SMK1? (iv) How does Sclerotinia modulate the redox environment in both host and pathogen? While addressing these questions, our main findings include the identification and characterization the NADPH oxidase (NOX) family in S. sclerotiorum. Silencing of Ssnox1 indicated a central role for this enzyme in both virulence and pathogenic (sclerotial) development, while inactivation of Ssnox2 resulted in limited sclerotial development but remained fully pathogenic. Interestingly, we found a consistent correlation with Ssnox1(involved with pathogenicity) and oxalate levels. This same observation was also noted with Sssod1. Thus, fungal enzymes involved in oxidative stress tolerance,when inactivated, also exhibit reduced OA levels. We have also shown that protein phosphatases (specifically PP2A and PTP1) are involved in morphogenesis and pathogenesis of S. sclerotiorum, demonstrating the regulatory role of these key proteins in the mentioned processes. While probing the redox environment and host-pathogen interactions we determined that oxalic acid is an elicitor of plant programmed cell death during S. sclerotiorum disease development and that oxalic acid suppresses host defense via manipulation of the host redox environment. During the course of this project we also contributed to the progress of understanding S. sclerotiorum function and the manipulation of this fungus by establishing an efficient gene replacement and direct hyphal transformation protocols in S. sclerotiorum. Lastly, both PIs were involved in thegenomic analysis of this necrotrophic fungal pathogen (along with Botrytis cinerea). Our results have been published in 11 papers (including joint papers and refereed reviews) and have set the basis for a continuum towards a better understanding and eventual control of this important pathogen (with implications to other fungal-host systems as well).
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'PTPN14' for particular source types:
Journal articles Dissertations / Theses
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography