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Protein phosphatase

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https://www.readbyqxmd.com/read/29351427/role-of-ptp1b-in-pomc-neurons-during-chronic-high-fat-diet-sex-differences-in-regulation-of-liver-lipids-and-glucose-tolerance
#1
Nicola Aberdein, Robert J Dambrino, Jussara M do Carmo, Zhen Wang, Laura E Mitchell, Heather A Drummond, John E Hall
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin receptor signalling and may contribute to leptin resistance in diet-induced obesity. Although PTP1B inhibition has been suggested as a potential weight loss therapy, the role of specific neuronal PTP1B signalling in cardiovascular and metabolic regulation and the importance of sex differences in this regulation are still unclear. In this study, we investigated the impact of pro-opiomelanocortin (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female mice fed a high fat diet (HFD)...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29351408/choroid-plexus-epithelial-cells-express-the-adhesion-protein-p-cadherin-at-cell-cell-contacts-and-syntaxin-4-in-the-luminal-membrane-domain
#2
Inga Baasch Christensen, Esben Nees Mogensen, Helle Hasager Damkier, Jeppe Praetorius
The choroid plexus epithelial cells (CPECs) belong to a small group of polarized cells, where the Na+,K+-ATPase is expressed in the luminal membrane. The basic polarity of the cells is, therefore, still debated. We investigated the subcellular distribution of an array of proteins known to play fundamental roles in either in establishing and maintaining basic cell polarity or the polarized delivery and recycling of plasma membrane proteins. Immunofluorescence histochemical analysis was applied to determine the subcellular localization of apical and basolateral membrane determinants...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29350681/aav-9-mediated-phosphatase-1-inhibitor-1-overexpression-improves-cardiac-contractility-in-unchallenged-mice-but-is-deleterious-in-pressure-overload
#3
D M Schwab, L Tilemann, R Bauer, M Heckmann, A Jungmann, M Wagner, J Burgis, C Vettel, H A Katus, A El-Armouche, O J Müller
The downregulation of β-adrenergic receptors (β-AR) and decreased cAMP-dependent protein kinase activity in failing hearts results in decreased phosphorylation and inactivation of phosphatase-inhibitor-1 (I-1), a distal amplifier element of β-adrenergic signaling, leading to increased protein phosphatase 1 activity and dephosphorylation of key phosphoproteins, including phospholamban. Downregulated and hypophosphorylated I-1 likely contributes to β-AR desensitization; therefore its modulation is a promising approach in heart failure treatment...
January 19, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29350465/proteomics-analysis-of-skeletal-muscle-from-leptin-deficient-ob-ob-mice-reveals-adaptive-remodeling-of-metabolic-characteristics-and-fiber-type-composition
#4
Milena Schönke, Marie Björnholm, Alexander V Chibalin, Juleen R Zierath, Atul S Deshmukh
Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis of type 2 diabetes, may be a cause or consequence of altered protein expressions profiles. Proteomics technology offers enormous promise to investigate molecular mechanisms underlying pathologies, however, the analysis of skeletal muscle is challenging. Using state-of-the-art multi-enzyme digestion and filter-aided sample preparation (MED-FASP) and a mass spectrometry (MS) based workflow, we performed a global proteomics analysis of skeletal muscle from leptin-deficient, obese, insulin resistant (ob/ob) and lean mice in mere two fractions in a short time (8 hours/sample)...
January 19, 2018: Proteomics
https://www.readbyqxmd.com/read/29349632/growth-performance-and-protective-effect-of-vitamin-e-on-oxidative-stress-pufferfish-takifugu-obscurus-following-by-ammonia-stress
#5
Chang-Hong Cheng, Zhi-Xun Guo, An-Li Wang
This study was conducted to determine the effects of vitamin E on growth performance, biochemical parameters, and antioxidant capacity of pufferfish (Takifugu obscurus) exposed to ammonia stress. The experimental basal diets supplemented with vitamin E at the rates of 2.31 (control), 21.84, 40.23, 83.64, 158.93, and 311.64 mg kg-1 dry weight were fed to fish for 60 days. After the feeding trial, the fish were exposed to 100 mg L-1 ammonia-nitrogen for 48 h. The results shown that the vitamin E group significantly improved weight gain, specific growth rate, and the expression levels of growth hormone receptors and insulin-like growth factor...
January 18, 2018: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29348710/the-protein-tyrosine-phosphatase-nonreceptor-22-ptpn22-r620w-functional-polymorphism-in-psoriasis
#6
Ghaleb Bin Huraib, Fahad Al Harthi, Misbahul Arfin, Sadaf Rizvi, Abdulrahaman Al-Asmari
Background: Psoriasis is a complex autoimmune disease caused by the interaction of genetic and environmental factors. PTPN22 gene polymorphism has been reported to affect psoriasis susceptibility; however, no data are available for Middle Eastern populations. Objective: The aim of this study was to investigate the association of PTPN22 (1858C/T) R620W polymorphism with psoriasis in a Saudi cohort. Methods: Saudi subjects (n = 306) including patients with psoriasis (n = 106) and matched controls (n = 200) were studied for PTPN22 variants using tetra-primer amplification refractory mutation system-polymerase chain reaction method...
2018: Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29348579/structural-basis-of-salm5-induced-ptp%C3%AE-dimerization-for-synaptic-differentiation
#7
Zhaohan Lin, Jianmei Liu, Huandi Ding, Fei Xu, Heli Liu
SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic differentiation through binding to the LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that have been highlighted as presynaptic hubs for synapse formation. The mechanisms underlying SALM5/LAR-RPTP interaction remain unsolved. Here we report crystal structures of human SALM5 LRR-Ig alone and in complex with human PTPδ Ig1-3 (MeA-). Distinct from other LAR-RPTP ligands, SALM5 mainly exists as a dimer with LRR domains from two protomers packed in an antiparallel fashion...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348454/harnessing-insulin-and-leptin-induced-oxidation-of-ptp1b-for-therapeutic-development
#8
Navasona Krishnan, Christopher A Bonham, Ioana A Rus, Om Kumar Shrestha, Carla M Gauss, Aftabul Haque, Ante Tocilj, Leemor Joshua-Tor, Nicholas K Tonks
The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348429/structural-basis-of-trans-synaptic-interactions-between-ptp%C3%AE-and-salms-for-inducing-synapse-formation
#9
Sakurako Goto-Ito, Atsushi Yamagata, Yusuke Sato, Takeshi Uemura, Tomoko Shiroshima, Asami Maeda, Ayako Imai, Hisashi Mori, Tomoyuki Yoshida, Shuya Fukai
Synapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPδ, PTPσ and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29347844/docking-analysis-targeted-to-the-whole-enzyme-an-application-to-the-prediction-of-inhibition-of-ptp1b-by-thiomorpholine-and-thiazolyl-derivatives
#10
C A Ganou, P Th Eleftheriou, P Theodosis-Nobelos, M Fesatidou, A A Geronikaki, T Lialiaris, E A Rekka
PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b has become a drug target for the treatment of type II diabetes. In the present study, prediction of inhibition using docking analysis targeted specifically to the active or allosteric site was performed on 87 compounds structurally belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and 10 thiazolyl derivatives exhibiting the best prediction results, were selected for in vitro evaluation...
February 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#11
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345291/microrna-1271-functions-as-a-metastasis-and-epithelial-mesenchymal-transition-inhibitor-in-human-hcc-by-targeting-the-ptp4a1-c-src-axis
#12
Chao Li, Yezhen Jiang, Runchen Miao, Kai Qu, Jingyao Zhang, Chang Liu
MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29345052/hpap-a-novel-regulatory-protein-with-atpase-and-phosphatase-activity-contributes-to-full-virulence-in-xanthomonas-campestris-pv-campestris
#13
Ping Cui, Rui-Fang Li, Da-Pei Zhang, Ji-Liang Tang, Guang-Tao Lu
The ability of the bacterial phytopathogen Xanthomonas campestris pv. campestris (Xcc) to cause disease is dependent on the type III secretion system (T3SS). Proteins of the Xcc T3SS are encoded by hrp (hypersensitive response and pathogenicity) genes and whose expression is mainly controlled by the regulators HrpG and HrpX. Here, we describe the identification and characterization of a previously unknown regulatory protein (named HpaP), which plays important role in hrp gene expression and virulence in Xcc...
January 18, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29344832/mitogen-activated-protein-kinase-6-and-map-kinase-phosphatase-1-are-involved-in-the-response-of-arabidopsis-roots-to-l-glutamate
#14
Jesús Salvador López-Bucio, Javier Raya-González, Gustavo Ravelo-Ortega, León Francisco Ruiz-Herrera, Maricela Ramos-Vega, Patricia León, José López-Bucio, Ángel Arturo Guevara-García
The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood...
January 17, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29344831/interaction-network-of-core-aba-signaling-components-in-maize
#15
Ying-Ge Wang, Feng-Ling Fu, Hao-Qiang Yu, Tao Hu, Yuan-Yuan Zhang, Yi Tao, Jian-Kang Zhu, Yang Zhao, Wan-Chen Li
We defined a comprehensive core ABA signaling network in monocot maize, including the gene expression, subcellular localization and interaction network of ZmPYLs, ZmPP2Cs, ZmSnRK2s and the putative substrates. The phytohormone abscisic acid (ABA) plays an important role in plant developmental processes and abiotic stress responses. In Arabidopsis, ABA is sensed by the PYL ABA receptors, which leads to binding of the PP2C protein phosphatase and activation of the SnRK2 protein kinases. These components functioning diversely and redundantly in ABA signaling are little known in maize...
January 17, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29344730/skeletal-dissemination-in-paget-s-disease-of-the-spine
#16
REVIEW
Tim Rolvien, Sebastian Butscheidt, Jozef Zustin, Michael Amling
PURPOSE: Paget's disease of bone (PDB) is a common skeletal disorder that is associated with locally increased bone turnover, skeletal deformity and pain. We report a case of skeletal dissemination in PDB of the spine. METHODS: Case report. RESULTS: A 46-year-old former professional athlete suffered from disseminated PDB throughout the spine and hips after various surgical interventions including spondylodesis, bone grafting and bone morphogenetic protein (rhBMP-2) administration...
January 17, 2018: European Spine Journal
https://www.readbyqxmd.com/read/29344643/microrna-23a-5p-regulates-osteogenic-differentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells-by-targeting-mitogen-activated-protein-kinase-13
#17
Gang Ren, Jing Sun, Meng-Meng Li, Yong-Dong Zhang, Rong-Hua Li, Yu-Ming Li
The molecular mechanisms of osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remain to be fully elucidated. MicroRNAs (miRs) serve vital roles in the process of regulating osteogenic differentiation of BMSCs. The present study aimed to investigate the role of miR‑23a‑5p in osteogenic differentiation of human (h)BMSCs, and the underlying molecular mechanism. The results of reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑23a‑5p was significantly downregulated in the process of osteogenic differentiation...
January 18, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344249/estradiol-suppresses-phosphorylation-of-er%C3%AE-serine-167-through-upregulation-of-pp2a-in-breast-cancer-cells
#18
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343782/protein-phosphatase-5-regulates-titin-phosphorylation-and-function-at-a-sarcomere-associated-mechanosensor-complex-in-cardiomyocytes
#19
Judith Krysiak, Andreas Unger, Lisa Beckendorf, Nazha Hamdani, Marion von Frieling-Salewsky, Margaret M Redfield, Cris G Dos Remedios, Farah Sheikh, Ulrich Gergs, Peter Boknik, Wolfgang A Linke
Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343725/the-phosphatase-ppm1a-controls-monocyte-to-macrophage-differentiation
#20
Samuel R Smith, Kaitlyn Schaaf, Nusrah Rajabalee, Frederic Wagner, Alexandra Duverger, Olaf Kutsch, Jim Sun
Differentiation of circulating monocytes into tissue-bound or tissue-resident macrophages is a critical regulatory process affecting host defense and inflammation. However, the regulatory signaling pathways that control the differentiation of monocytes into specific and distinct functional macrophage subsets are poorly understood. Herein, we demonstrate that monocyte-to-macrophage differentiation is controlled by the Protein Phosphatase, Mg2+/Mn2+-dependent 1A (PPM1A). Genetic manipulation experiments demonstrated that overexpression of PPM1A attenuated the macrophage differentiation program, while knockdown of PPM1A expression accelerated the ability of monocytes to differentiate into macrophages...
January 17, 2018: Scientific Reports
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