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PTP1B

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https://www.readbyqxmd.com/read/27908790/mpp-inhibits-mglur1-5-mediated-long-term-depression-in-mouse-hippocampus-by-calpain-activation
#1
Junyao Li, Hui Chen, Shengbing Wu, Yuefa Cheng, Qinglin Li, Jing Wang, Guoqi Zhu
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses...
November 28, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27890939/the-metal-face-of-protein-tyrosine-phosphatase-1b
#2
REVIEW
Elisa Bellomo, Kshetrimayum Birla Singh, Alberto Massarotti, Christer Hogstrand, Wolfgang Maret
A new paradigm in metallobiochemistry describes the activation of inactive metalloenzymes by metal ion removal. Protein tyrosine phosphatases (PTPs) do not seem to require a metal ion for enzymatic activity. However, both metal cations and metal anions modulate their enzymatic activity. One binding site is the phosphate binding site at the catalytic cysteine residue. Oxyanions with structural similarity to phosphate, such as vanadate, inhibit the enzyme with nanomolar to micromolar affinities. In addition, zinc ions (Zn(2+)) inhibit with picomolar to nanomolar affinities...
November 15, 2016: Coordination Chemistry Reviews
https://www.readbyqxmd.com/read/27872190/ptp1b-in-calpain-dependent-feedback-regulation-of-vegfr2-in-endothelial-cells-implication-in-vegf-dependent-angiogenesis-and-diabetic-wound-healing
#3
Yixuan Zhang, Qiang Li, Ji Youn Youn, Hua Cai
The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We have previously discovered a novel role of calpain in mediating VEGF-induced PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible feedbak regulation of VEGFR2 by calpain via its substrate protein phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF-induced angiogenesis, especially in diabetic wound healing. Over-expression of PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic endothelial cells, while PTP1B siRNA increased both, implicating the negative regulation of VEGFR2 by PTP1B...
November 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27871946/trivaric-acid-a-new-inhibitor-of-ptp1b-with-potent-beneficial-effect-on-diabetes
#4
Wenlong Sun, Bowei Zhang, Haizhou Zheng, Chunlin Zhuang, Xia Li, Xinhua Lu, Chunshan Quan, Yuesheng Dong, Zhihui Zheng, Zhilong Xiu
AIM: To screen a potential PTP1b inhibitor from the microbial origin-based compound library and to investigate the potential anti-diabetic effects of the inhibitor in vivo and determine its primary anti-diabetic mechanism in vitro and in silico. METHODS: PTP1b inhibitory activity was measured using recombination protein as the enzyme and p-NPP as the substrate. The binding of the inhibitor to PTP1b was analysed by docking in silico and confirmed by ITC experiments...
November 18, 2016: Life Sciences
https://www.readbyqxmd.com/read/27866320/protein-tyrosine-phosphatase-1b-inhibitory-properties-of-seco-cucurbitane-triterpenes-obtained-from-fruiting-bodies-of-russula-lepida
#5
Wilmar Maarisit, Hiroyuki Yamazaki, Syu-Ichi Kanno, Ayako Tomizawa, Jong-Soo Lee, Michio Namikoshi
The known seco-cucurbitane triterpene, (24E)-3,4-seco-cucurbita-4,24-diene-3,26,29-trioic acid (1), has been isolated as a potent protein tyrosine phosphatase (PTP) 1B inhibitor together with a new analogue, (24E)-3,4-seco-cucurbita-4,24-diene-3-hydroxy-26,29-dioic acid (2), from the fruiting bodies of Russula lepida. Further evaluation of their biological properties against PTPs revealed that compound 1 inhibited T-cell PTP activity similarly to PTP1B and exhibited moderate selectivity against PTP1B over vaccinia H-1-related phosphatase...
November 19, 2016: Journal of Natural Medicines
https://www.readbyqxmd.com/read/27855221/cell-transformation-by-ptp1b-truncated-mutants-found-in-human-colon-and-thyroid-tumors
#6
Wenhan Mei, Kemin Wang, Jian Huang, Xinmin Zheng
Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail...
2016: PloS One
https://www.readbyqxmd.com/read/27842892/discovery-of-4-5-arylidene-4-oxothiazolidin-3-yl-methyl-benzoic-acid-derivatives-active-as-novel-potent-allosteric-inhibitors-of-protein-tyrosine-phosphatase-1b-in-silico-studies-and-in%C3%A2-vitro-evaluation-as-insulinomimetic-and-anti-inflammatory-agents
#7
Rosaria Ottanà, Paolo Paoli, Alexandra Naß, Giulia Lori, Venera Cardile, Ilenia Adornato, Archimede Rotondo, Adriana Carol Eleonora Graziano, Gerhard Wolber, Rosanna Maccari
New 4-{[5-arylidene-2-(4-fluorophenylimino)-4-oxothiazolidin-3-yl]methyl}benzoic acids (5) and 2-thioxo-4-thiazolidinone analogues (6) were synthesised as a part of a continuing search for new inhibitors of protein tyrosine phosphatase 1B (PTP1B), an enzyme which is implicated in metabolic disorders and inflammatory signaling. Most of the tested compounds were shown to be potent PTP1B inhibitors. Moreover, their inhibition mechanism was markedly influenced by the substituents in the positions 2 and 5, as kinetic studies indicated...
November 1, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27826746/protein-tyrosine-phosphatase-1b-ptp1b-is-required-for-cardiac-lineage-differentiation-of-mouse-embryonic-stem-cells
#8
Zahra Shokati Eshkiki, Mohammad Hossein Ghahremani, Parisa Shabani, Sattar Gorgani Firuzjaee, Asie Sadeghi, Hossein Ghanbarian, Reza Meshkani
Protein tyrosine phosphatase 1B (PTP1B) has been shown to regulate multiple cellular events such as differentiation, cell growth, and proliferation; however, the role of PTP1B in differentiation of embryonic stem (ES) cells into cardiomyocytes remains unexplored. In the present study, we investigated the effects of PTP1B inhibition on differentiation of ES cells into cardiomyocytes. PTP1B mRNA and protein levels were increased during the differentiation of ES cells into cardiomyocytes. Accordingly, a stable ES cell line expressing PTP1B shRNA was established...
November 8, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27824079/mena-inv-dysregulates-cortactin-phosphorylation-to-promote-invadopodium-maturation
#9
Maxwell D Weidmann, Chinmay R Surve, Robert J Eddy, Xiaoming Chen, Frank B Gertler, Ved P Sharma, John S Condeelis
Invadopodia, actin-based protrusions of invasive carcinoma cells that focally activate extracellular matrix-degrading proteases, are essential for the migration and intravasation of tumor cells during dissemination from the primary tumor. We have previously shown that cortactin phosphorylation at tyrosine residues, in particular tyrosine 421, promotes actin polymerization at newly-forming invadopodia, promoting their maturation to matrix-degrading structures. However, the mechanism by which cells regulate the cortactin tyrosine phosphorylation-dephosphorylation cycle at invadopodia is unknown...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799335/functional-impairment-of-murine-dendritic-cell-subsets-following-infection-with-infective-larval-stage-3-of-brugia-malayi
#10
Aditi Sharma, Pankaj Sharma, Achchhe Lal Vishwakarma, Mrigank Srivastava
Filarial parasites cause functional impairment of host Dendritic cells (DCs). However, effects of early infection on individual DC subsets are not known. In this study, we infected BALB/c mice with infective larvae stage-3 of lymphatic filarial parasite Brugia malayi (Bm-L3) and studied its effect on FACS-sorted DC subsets. While Myeloid DCs (mDCs) accumulated within day 3 post-infection (p.i.), Lymphoid DCs (LDCs) and CD8(+) Plasmacytoid DCs (pDCs) peaked at day 7 p.i. in the spleens and mesenteric lymph nodes (mLNs) of infected mice...
October 31, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27798765/prunin-is-a-highly-potent-flavonoid-from-prunus-davidiana-stems-that-inhibits-protein-tyrosine-phosphatase-1b-and-stimulates-glucose-uptake-in-insulin-resistant-hepg2-cells
#11
Hyun Ah Jung, Md Yousof Ali, Himanshu Kumar Bhakta, Byung-Sun Min, Jae Sue Choi
Prunin is the main flavonoid in Prunus davidiana stems and improves hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. The aim of this study was to investigate the in vitro anti-diabetic potential of prunin via the inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, peroxynitrite (ONOO(-))-mediated tyrosine nitration, and stimulation of glucose uptake in insulin-resistant hepatocytes. In addition, a molecular docking simulation was performed to predict specific prunin binding modes during PTP1B inhibition...
October 31, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27790059/comparative-analysis-of-protein-tyrosine-phosphatases-regulating-microglial-activation
#12
Gyun Jee Song, Jaehong Kim, Jong-Heon Kim, Seungeun Song, Hana Park, Zhong-Yin Zhang, Kyoungho Suk
Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS)...
October 2016: Experimental Neurobiology
https://www.readbyqxmd.com/read/27769948/protein-tyrosine-phosphatase-1b-and-%C3%AE-glucosidase-inhibitory-activities-of-pueraria-lobata-root-and-its-constituents
#13
Su Hui Seong, Anupom Roy, Hyun Ah Jung, Hee Jin Jung, Jae Sue Choi
ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata root was used to treat wasting-thirst regarded as diabetes mellitus and was included in the composition of Okcheonsan, which is prescribed for thirst-waste in traditional Chinese medicine. AIM OF THE STUDY: The objective of this study was to evaluate the anti-diabetic potential of the root of Pueraria lobata and its constituents via protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities. MATERIALS AND METHODS: In this study, anti-diabetic activities of the 70% ethanolic (EtOH) extract from P...
October 18, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27757011/druggability-analysis-and-classification-of-protein-tyrosine-phosphatase-active-sites
#14
Mohammad A Ghattas, Noor Raslan, Asil Sadeq, Mohammad Al Sorkhy, Noor Atatreh
Protein tyrosine phosphatases (PTP) play important roles in the pathogenesis of many diseases. The fact that no PTP inhibitors have reached the market so far has raised many questions about their druggability. In this study, the active sites of 17 PTPs were characterized and assessed for its ability to bind drug-like molecules. Consequently, PTPs were classified according to their druggability scores into four main categories. Only four members showed intermediate to very druggable pocket; interestingly, the rest of them exhibited poor druggability...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27752061/protein-tyrosine-phosphatase-1b-targets-pitx1-p120rasgap-thus-showing-therapeutic-potential-in-colorectal-carcinoma
#15
Hao-Wei Teng, Man-Hsin Hung, Li-Ju Chen, Mao-Ju Chang, Feng-Shu Hsieh, Ming-Hsien Tsai, Jui-Wen Huang, Chih-Lung Lin, Hsiang-Wen Tseng, Zong-Keng Kuo, Jeng-Kai Jiang, Shung-Haur Yang, Chung-Wai Shiau, Kuen-Feng Chen
Protein tyrosine phosphatase 1B (PTP1B) is known to promote the pathogenesis of diabetes and obesity by negatively regulating insulin and leptin pathways, but its role associated with colon carcinogenesis is still under debate. In this study, we demonstrated the oncogenic role of PTP1B in promoting colon carcinogenesis and predicting worse clinical outcomes in CRC patients. By co-immunoprecipitation, we showed that PITX1 was a novel substrate of PTP1B. Through direct dephosphorylation at Y160, Y175 and Y179, PTP1B destabilized PITX1, which resulted in downregulation of the PITX1/p120RasGAP axis...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27702761/senp1-regulates-ifn-%C3%AE-stat1-signaling-through-stat3-socs3-negative-feedback-loop
#16
Tingting Yu, Yong Zuo, Rong Cai, Xian Huang, Shuai Wu, Chenxi Zhang, Y Eugene Chin, Dongdong Li, Zhenning Zhang, Nansong Xia, Qi Wang, Hao Shen, Xuebiao Yao, Zhong-Yin Zhang, Song Xue, Lei Shen, Jinke Cheng
Interferon-γ (IFN-γ) triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. SOCS1 and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here we identify a novel negative feedback loop mediated by STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B (PTP1B), in IFN-γ signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3...
October 4, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27649447/structural-basis-of-fullerene-derivatives-as-novel-potent-inhibitors-of-protein-tyrosine-phosphatase-1b-insight-into-the-inhibitory-mechanism-through-molecular-modeling-studies
#17
Mengdan Qian, Yaming Shan, Shanshan Guan, Hao Zhang, Song Wang, Weiwei Han
Protein tyrosine phosphatase 1B (PTP1B) has become an outstanding target for the treatment of diabetes and obesity. Recent research has demonstrated that some fullerene derivatives serve as a new nanoscale-class of potent inhibitors of PTP1B, but the specific mechanism remains unclear. Several molecular modeling methods (molecular docking, molecular dynamics simulations, and molecular mechanics/generalized Born surface area calculations) were integrated to provide insight into the binding mode and inhibitory mechanism of the new class of fullerene inhibitors...
October 3, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/27596049/role-of-protein-tyrosine-phosphatase-1b-in-cardiovascular-diseases
#18
Pierre-Alain Thiebaut, Marie Besnier, Elodie Gomez, Vincent Richard
Protein Tyrosine Phosphatase 1B (PTP1B) is mostly involved in negative regulation of signaling mediated by Tyrosine Kinase Receptors, especially the insulin and leptin receptors. This enzyme thus plays a major role in the development of diseases associated with insulin resistance, such as obesity and diabetes. PTP1B inhibition is currently considered as an attractive treatment of insulin resistance and associated metabolic disorders. In parallel, emerging evidence also suggests that PTP1B is widely expressed in cardiovascular tissues, notably in the heart and the endothelium, and that it could also be a potential treatment of several cardiovascular diseases...
September 3, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27559126/menainv-mediates-synergistic-cross-talk-between-signaling-pathways-driving-chemotaxis-and-haptotaxis
#19
Madeleine J Oudin, Miles A Miller, Joelle A Z Klazen, Tatsiana Kosciuk, Alisha Lussiez, Shannon K Hughes, Jenny Tadros, James E Bear, Douglas A Lauffenburger, Frank B Gertler
Directed cell migration, a key process in metastasis, arises from the combined influence of multiple processes, including chemotaxis-the directional movement of cells to soluble cues-and haptotaxis-the migration of cells on gradients of substrate-bound factors. However, it is unclear how chemotactic and haptotactic pathways integrate with each other to drive overall cell behavior. Mena(INV) has been implicated in metastasis by driving chemotaxis via dysregulation of phosphatase PTP1B and more recently in haptotaxis via interaction with integrin α5β1...
October 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27548130/protein-tyrosine-phosphatase-1b-inhibitors-from-the-stems-of-akebia-quinata
#20
Jin-Pyo An, Thi Kim Quy Ha, Jinwoong Kim, Tae Oh Cho, Won Keun Oh
PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2-14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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