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https://www.readbyqxmd.com/read/27725732/three-dimensional-electron-microscopy-reveals-the-evolution-of-glomerular-barrier-injury
#1
Michael J Randles, Sophie Collinson, Tobias Starborg, Aleksandr Mironov, Mira Krendel, Eva Königshausen, Lorenz Sellin, Ian S D Roberts, Karl E Kadler, Jeffrey H Miner, Rachel Lennon
Glomeruli are highly sophisticated filters and glomerular disease is the leading cause of kidney failure. Morphological change in glomerular podocytes and the underlying basement membrane are frequently observed in disease, irrespective of the underlying molecular etiology. Standard electron microscopy techniques have enabled the identification and classification of glomerular diseases based on two-dimensional information, however complex three-dimensional ultrastructural relationships between cells and their extracellular matrix cannot be easily resolved with this approach...
October 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27345410/ptpro-represses-erbb2-driven-breast-oncogenesis-by-dephosphorylation-and-endosomal-internalization-of-erbb2
#2
H Dong, L Ma, J Gan, W Lin, C Chen, Z Yao, L Du, L Zheng, C Ke, X Huang, H Song, R Kumar, S C Yeung, H Zhang
The plasma membrane-associated tyrosine phosphatase PTPRO is frequently transcriptionally repressed in cancers and signifies poor prognosis of breast cancer patients. In this study, deletion of Ptpro in MMTV-Erbb2 transgenic mice dramatically shortened the mammary tumor latency and accelerated tumor growth due to loss of Ptpro within the breast cancer cells but not in surrounding tissue as confirmed by hetero-transplantation studies. Both in vitro and in vivo data demonstrated that the phosphatase activity was required for the inactivation of ERBB2 and its downstream signaling...
June 27, 2016: Oncogene
https://www.readbyqxmd.com/read/27272414/genome-wide-association-study-of-acute-renal-graft-rejection
#3
L Ghisdal, C Baron, Y Lebranchu, O Viklický, A Konarikova, M Naesens, D Kuypers, M Dinic, E Alamartine, G Touchard, T Antoine, M Essig, J P Rerolle, P Merville, J L Taupin, Y Le Meur, A Grall-Jezequel, F Glowacki, C Noël, C Legendre, D Anglicheau, N Broeders, W Coppieters, E Docampo, M Georges, Z Ajarchouh, A Massart, J Racapé, D Abramowicz, M Abramowicz
Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls, on Illumina 2·5 M arrays. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant SNPs from the discovery cohort...
June 7, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26434819/tumor-suppression-mechanisms-of-protein-tyrosine-phosphatase-o-and-clinical-applications
#4
REVIEW
Man-Man Kang, Shun-Lin Shan, Xu-Yang Wen, Hu-Sheng Shan, Zheng-Jun Wang
Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/26303994/aggravated-liver-injury-but-attenuated-inflammation-in-ptpro-deficient-mice-following-lps-d-gain-induced-fulminant-hepatitis
#5
Xiaochen Wang, Shushan Yan, Donghua Xu, Jun Li, Yu Xie, Jiajie Hou, Runqiu Jiang, Chuanyong Zhang, Beicheng Sun
BACKGROUND/AIMS: Critical roles of PTPRO and TLR4 have been implicated in hepatocellular carcinoma. However, little is known about their modifying effects on inflammation-related diseases in liver, particularly fulminant hepatitis (FH). We aim to investigate the potential role of PTPRO and its interaction with TLR4 in LPS/D-GaIN induced FH. METHODS: A LPS/D-GaIN induced mouse FH model was used. RAW264.7 cells were transfected with PTPRO over-expressed lentiviral plasmids for further investigation...
2015: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26117839/ptprot-maintains-t-cell-immunity-in-the-microenvironment-of-hepatocellular-carcinoma
#6
Jiajie Hou, Lei Deng, Han Zhuo, Zhe Lin, Yun Chen, Runqiu Jiang, Dianyu Chen, Xudong Zhang, Xingxu Huang, Beicheng Sun
Intratumoral T cells play a central role in anti-tumor immunity, and the balance between T effector cells (Teff) and regulatory T cells (Treg) affects the prognosis of cancer patients. However, educated by tumor microenvironment, T cells frequently fail in their responsibility. In this study, we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-type O (PTPROt) in T cell-mediated anti-tumor immunity. We recruited 70 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers for clinical investigation, and analyzed cellular tumor immunity by using ptpro(-/-) C57BL/6 mice and NOD/SCID mice...
August 2015: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/26063811/the-r3-receptor-like-protein-tyrosine-phosphatase-subfamily-inhibits-insulin-signalling-by-dephosphorylating-the-insulin-receptor-at-specific-sites
#7
Takafumi Shintani, Satoru Higashi, Yasushi Takeuchi, Eugenio Gaudio, Francesco Trapasso, Alfredo Fusco, Masaharu Noda
The autophosphorylation of specific tyrosine residues occurs in the cytoplasmic region of the insulin receptor (IR) upon insulin binding, and this in turn initiates signal transduction. The R3 subfamily (Ptprb, Ptprh, Ptprj and Ptpro) of receptor-like protein tyrosine phosphatases (RPTPs) is characterized by an extracellular region with 6-17 fibronectin type III-like repeats and a cytoplasmic region with a single phosphatase domain. We herein identified the IR as a substrate for R3 RPTPs by using the substrate-trapping mutants of R3 RPTPs...
September 2015: Journal of Biochemistry
https://www.readbyqxmd.com/read/25918036/renal-mechanisms-of-association-between-fibroblast-growth-factor-1-and-blood-pressure
#8
Maciej Tomaszewski, James Eales, Matthew Denniff, Stephen Myers, Guat Siew Chew, Christopher P Nelson, Paraskevi Christofidou, Aishwarya Desai, Cara Büsst, Lukasz Wojnar, Katarzyna Musialik, Jacek Jozwiak, Radoslaw Debiec, Anna F Dominiczak, Gerjan Navis, Wiek H van Gilst, Pim van der Harst, Nilesh J Samani, Stephen Harrap, Pawel Bogdanski, Ewa Zukowska-Szczechowska, Fadi J Charchar
The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P = 9.65 × 10(-5)) and diastolic BP (P = 7.61 × 10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9...
December 2015: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/25826083/ptpro-mediated-autophagy-prevents-hepatosteatosis-and-tumorigenesis
#9
Wenjie Zhang, Jiajie Hou, Xiaochen Wang, Runqiu Jiang, Yin Yin, Jie Ji, Lei Deng, Xingxu Huang, Ke Wang, Beicheng Sun
Autophagy plays a critical role in the progression of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Protein tyrosine phosphatase receptor type O (PTPRO) was recently identified as a tumor suppressor, but little is known about its role in NASH. Here, we investigated the role of PTPRO-dependent autophagy in insulin resistance, lipid metabolism, and hepatocarcinogenesis. Wild-type (WT) and ptpro-/- mice were fed a high-fat diet (HFD) for another 16 weeks after diethylnitrosamine (DEN) injection to induce NASH...
April 20, 2015: Oncotarget
https://www.readbyqxmd.com/read/25752595/nature-and-nurture-a-case-of-transcending-haematological-pre-malignancies-in-a-pair-of-monozygotic-twins-adding-possible-clues-on-the-pathogenesis-of-b-cell-proliferations
#10
Marcus C Hansen, Charlotte G Nyvold, Anne S Roug, Eigil Kjeldsen, Palle Villesen, Line Nederby, Peter Hokland
We describe a comprehensive molecular analysis of a pair of monozygotic twins, who came to our attention when one experienced amaurosis fugax and was diagnosed with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic B-cell chronic lymphocytic leukaemia (B-CLL). Although JAK2-, Twin B was subsequently shown to have a benign monoclonal B-cell lymphocytosis (MBL). Flow cytometric and molecular analyses of the B-cell compartments revealed different immunoglobulin light and heavy chain usage in each twin...
May 2015: British Journal of Haematology
https://www.readbyqxmd.com/read/25646811/protein-tyrosine-phosphatase-receptor-type-o-expression-in-the-tumor-niche-correlates-with-reduced-tumor-growth-angiogenesis-circulating-tumor-cells-and-metastasis-of-breast-cancer
#11
Zhao Liu, Jiajie Hou, Lidong Ren, Jing He, Beicheng Sun, Lu-Zhe Sun, Shui Wang
Protein tyrosine phosphatase receptor type O (PTPRO) has been recognized as a tumor suppressor in various types of cancer cells. However, little attention has been given to the role of PTPRO expression in the tumor microenvironment. We aimed to reveal the role of PTPRO in the breast cancer niche. Py8119 mouse breast cancer cells were implanted orthotopically into female wild-type or ptpro-/- C57Bl/6 mice. We observed that the loss of PTPRO in the tumor niche was correlated with larger tumor volume, more metastases, increased number of circulating tumor cells (CTCs), less apoptosis and reduced necrosis rates in the orthotopic mouse model of breast cancer...
April 2015: Oncology Reports
https://www.readbyqxmd.com/read/25633279/ptpro-associated-hepatic-stellate-cell-activation-plays-a-critical-role-in-liver-fibrosis
#12
Xudong Zhang, Zhongming Tan, Youjing Wang, Junwei Tang, Runjiu Jiang, Jiajie Hou, Han Zhuo, Xiaochen Wang, Jie Ji, Xihu Qin, Beicheng Sun
BACKGROUND/AIMS: PTPRO (protein tyrosine phosphatase, receptor type O) is implicated in diverse physiological and pathological processes in cancer and hepatic ischemia/reperfusion injury, although little is known about its role in hepatic fibrosis. METHODS: Here, by using genetically deficient mice, we reported that PTPRO knockout (PTPRO(-/-)) significantly attenuated liver injury, release of inflammatory factors, tissue remodeling, and liver fibrosis in two experimental mouse models of fibrogenesis induced by bile-duct ligation or carbon tetrachloride administration...
2015: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/25480659/dna-methylation-alterations-in-response-to-prenatal-exposure-of-maternal-cigarette-smoking-a-persistent-epigenetic-impact-on-health-from-maternal-lifestyle
#13
Christina H Nielsen, Agnete Larsen, Anders L Nielsen
Despite increased awareness, maternal cigarette smoking during pregnancy continues to be a common habit causing risk for numerous documented negative health consequences in the exposed children. It has been proposed that epigenetic mechanisms constitute the link between prenatal exposure to maternal cigarette smoking (PEMCS) and the diverse pathologies arising in later life. We here review the current literature, focusing on DNA methylation. Alterations in the global DNA methylation patterns were observed after exposure to maternal smoking during pregnancy in placenta, cord blood and buccal epithelium tissue...
February 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/25339662/survival-and-inflammation-promotion-effect-of-ptpro-in-fulminant-hepatitis-is-associated-with-nf-%C3%AE%C2%BAb-activation
#14
Runqiu Jiang, Dianyu Chen, Jiajie Hou, Zhongming Tan, Youjing Wang, Xingxu Huang, Xuehao Wang, Beicheng Sun
Previous investigations demonstrated that protein tyrosine phosphatase, receptor type, O (PTPRO) acts as a tumor suppressor in liver cancer; however, little is known about its role in liver inflammation. Thus, we investigated the role of PTPRO in fulminant hepatitis (FH) using a Con A-induced mouse model. Significantly more severe liver damage, but attenuated inflammation, was detected in PTPRO-knockout (KO) mice, and PTPRO deficiency could confer this phenotype to wild-type mice in bone marrow transplantation...
November 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25301722/the-tyrosine-phosphatase-ptpro-sensitizes-colon-cancer-cells-to-anti-egfr-therapy-through-activation-of-src-mediated-egfr-signaling
#15
Layka Abbasi Asbagh, Iria Vazquez, Loredana Vecchione, Eva Budinska, Veerle De Vriendt, Maria Francesca Baietti, Mikhail Steklov, Bart Jacobs, Nicholas Hoe, Sharat Singh, Naga-Sailaja Imjeti, Pascale Zimmermann, Anna Sablina, Sabine Tejpar
Inappropriate activation of epidermal growth factor receptor (EGFR) plays a causal role in many cancers including colon cancer. The activation of EGFR by phosphorylation is balanced by receptor kinase and protein tyrosine phosphatase activities. However, the mechanisms of negative EGFR regulation by tyrosine phosphatases remain largely unexplored. Our previous results indicate that protein tyrosine phosphatase receptor type O (PTPRO) is down-regulated in a subset of colorectal cancer (CRC) patients with a poor prognosis...
October 30, 2014: Oncotarget
https://www.readbyqxmd.com/read/25273097/a-circulating-antibody-panel-for-pretransplant-prediction-of-fsgs-recurrence-after-kidney-transplantation
#16
Marianne Delville, Tara K Sigdel, Changli Wei, Jing Li, Szu-Chuan Hsieh, Alessia Fornoni, George W Burke, Patrick Bruneval, Maarten Naesens, Annette Jackson, Nada Alachkar, Guillaume Canaud, Christophe Legendre, Dany Anglicheau, Jochen Reiser, Minnie M Sarwal
Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of accelerated graft loss. To evaluate pathogenic antibodies (Abs) in rFSGS, we processed 141 serum samples from 64 patients with and without primary rFSGS and 34 non-FSGS control patients transplanted at four hospitals. We screened about 9000 antigens in pretransplant sera and selected 10 Abs targeting glomerular antigens for enzyme-linked immunosorbent assay (ELISA) validation. A panel of seven Abs (CD40, PTPRO, CGB5, FAS, P2RY11, SNRPB2, and APOL2) could predict posttransplant FSGS recurrence with 92% accuracy...
October 1, 2014: Science Translational Medicine
https://www.readbyqxmd.com/read/25034527/interaction-of-ptpro-and-tlr4-signaling-in-hepatocellular-carcinoma
#17
Donghua Xu, Xiaochen Wang, Shushan Yan, Yin Yin, Jiajie Hou, Xuehao Wang, Beicheng Sun
Protein tyrosine phosphatase receptor type O (PTPRO) has been identified as a tumor suppressor in a number of cancers including hepatocellular carcinoma (HCC). Toll-like receptor 4 (TLR4) plays diverse roles in HCC tumorigenesis and progression. The association between PTPRO and TLR4 signaling in HCC remains largely unknown. We aimed to clarify the interaction between PTPRO and TLR4 in HCC. Surprisingly, we found reduced and positive-related expression of TLR4 and PTPRO in 84 human HCC specimens. Increased TLR4 expression and activity was found in PTPRO-overexpressed HCC cells stimulated with lipopolysaccharide (LPS)...
October 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/24919593/aberrant-ptpro-methylation-in-tumor-tissues-as-a-potential-biomarker-that-predicts-clinical-outcomes-in-breast-cancer-patients
#18
Shao-ying Li, Rong Li, Yu-li Chen, Li-kuang Xiong, Hui-lin Wang, Lei Rong, Rong-cheng Luo
BACKGROUND: Aberrant hypermethylation of gene promoter regions is a primary mechanism by which tumor suppressor genes become inactivated in breast cancer. Epigenetic inactivation of the protein tyrosine phosphatase receptor-type O gene (PTPRO) has been described in several types of cancer. RESULTS: We screened primary breast cancer tissues for PTPRO promoter hypermethylation and assessed potential associations with pathological features and patient outcome. We also evaluated its potential as a breast cancer biomarker...
2014: BMC Genetics
https://www.readbyqxmd.com/read/24491805/developmental-co-expression-and-functional-redundancy-of-tyrosine-phosphatases-with-neurotrophin-receptors-in-developing-sensory-neurons
#19
Viktoria Tchetchelnitski, Monique van den Eijnden, Fanny Schmidt, Andrew W Stoker
Receptor-type protein tyrosine phosphatases (RPTPs) have been implicated as direct or indirect regulators of neurotrophin receptors (TRKs). It remains less clear if and how such RPTPs might regulate TRK proteins in vivo during development. Here we present a comparative expression profile of RPTP genes and Trk genes during early stages of murine, dorsal root ganglion maturation. We find little if any specific, temporal mRNA co-regulation between individual RPTP and Ntrk genes between E12.5 and E14.5. Moreover, a double fluorescent in-situ hybridization and immunofluorescence study of seven Rptp genes with Ntrks revealed widespread co-expression of RPTPs in individual neurons, but no tight correlation with Trk expression profiles...
May 2014: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/24359314/diverse-levels-of-sequence-selectivity-and-catalytic-efficiency-of-protein-tyrosine-phosphatases
#20
Nicholas G Selner, Rinrada Luechapanichkul, Xianwen Chen, Benjamin G Neel, Zhong-Yin Zhang, Stefan Knapp, Charles E Bell, Dehua Pei
The sequence selectivity of 14 classical protein-tyrosine phosphatases (PTPs) (PTPRA, PTPRB, PTPRC, PTPRD, PTPRO, PTP1B, SHP-1, SHP-2, HePTP, PTP-PEST, TCPTP, PTPH1, PTPD1, and PTPD2) was systematically profiled by screening their catalytic domains against combinatorial peptide libraries. All of the PTPs exhibit similar preference for pY peptides rich in acidic amino acids and disfavor positively charged sequences but differ vastly in their degrees of preference/disfavor. Some PTPs (PTP-PEST, SHP-1, and SHP-2) are highly selective for acidic over basic (or neutral) peptides (by >10(5)-fold), whereas others (PTPRA and PTPRD) show no to little sequence selectivity...
January 21, 2014: Biochemistry
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