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https://www.readbyqxmd.com/read/28726316/deprotonation-states-of-the-two-active-site-water-molecules-regulate-the-binding-of-protein-phosphatase-5-with-its-substrate-a-molecular-dynamics-study
#1
Lingyun Wang, Feng Yan
Protein phosphatase 5 (PP5), mainly localized in human brain, can dephosphorylate tau protein whose high level of phosphorylation is related to Alzheimer's disease. Similar to other protein phosphatases, PP5 has a conserved motif in the catalytic domain that contains two binding sites for manganese (Mn(2+) ) ions. Structural data indicate that two active site water molecules, one bridging the two Mn(2+) ions and the other terminally coordinated with one of the Mn(2+) ions (Mn1), are involved in catalysis. Recently, a density functional theory study revealed that the two water molecules can be both deprotonated to keep a neutral active site for catalysis...
July 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28701256/toll-like-receptor-expression-patterns-in-the-rat-uterus-during-post-partum-involution
#2
Emel Alan, Narin Liman
Toll-like receptors (TLRs) belong to a family of pathogen recognition receptors and play critical roles in detecting and responding to invading pathogens. TLR expression could be significant because, in the uterus, the reproductive tract is an important site of exposure to and infection by pathogens during the post partum involution period. To clarify the expression and localisation patterns of TLRs in the rat uterus on Days 1, 3, 5 and 10 post partum (PP1, PP3, PP5 and PP10 respectively), immunohistochemistry and western blotting were used to analyse TLR1-7, TLR9 and TLR10...
July 13, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28528695/protein-phosphatase-5-promotes-hepatocarcinogenesis-through-interaction-with-amp-activated-protein-kinase
#3
Yao-Li Chen, Man-Hsin Hung, Pei-Yi Chu, Tzu-I Chao, Ming-Hsien Tsai, Li-Ju Chen, Yung-Jen Hsiao, Chih-Ting Shih, Feng-Shu Hsieh, Kuen-Feng Chen
The serine-threonine protein phosphatase family members are known as critical regulators of various cellular functions, such as survival and transformation. Growing evidence suggests that pharmacological manipulation of phosphatase activity exhibits therapeutic benefits. Ser/Thr protein phosphatase 5 (PP5) is known to participate in glucocorticoid receptor (GR) and stress-induced signaling cascades that regulate cell growth and apoptosis, and has been shown to be overexpressed in various human malignant diseases...
August 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28526890/a-heteromeric-molecular-complex-regulates-the-migration-of-lung-alveolar-epithelial-cells-during-wound-healing
#4
Manik C Ghosh, Patrudu S Makena, Joseph Kennedy, Bin Teng, Charlean Luellen, Scott E Sinclair, Christopher M Waters
Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28453226/palbociclib-induces-activation-of-ampk-and-inhibits-hepatocellular-carcinoma-in-a-cdk4-6-independent-manner
#5
Feng-Shu Hsieh, Yao-Li Chen, Man-Hsin Hung, Pei-Yi Chu, Ming-Hsien Tsai, Li-Ju Chen, Yung-Jen Hsiao, Chih-Ting Shih, Mao-Ju Chang, Tzu-I Chao, Chung-Wai Shiau, Kuen-Feng Chen
Palbociclib, a CDK4/6 inhibitor, has recently been approved for hormone receptor-positive breast cancer patients. The effects of palbociclib as a treatment for other malignancies, including hepatocellular carcinoma (HCC), are of great clinical interest and are under active investigation. Here, we report the effects and a novel mechanism of action of palbociclib in HCC. We found that palbociclib induced both autophagy and apoptosis in HCC cells through a mechanism involving 5' AMP-activated protein kinase (AMPK) activation and protein phosphatase 5 (PP5) inhibition...
August 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28355257/lithic-technological-responses-to-late-pleistocene-glacial-cycling-at-pinnacle-point-site-5-6-south-africa
#6
Jayne Wilkins, Kyle S Brown, Simen Oestmo, Telmo Pereira, Kathryn L Ranhorn, Benjamin J Schoville, Curtis W Marean
There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change...
2017: PloS One
https://www.readbyqxmd.com/read/28348577/deciphering-the-roles-of-thiazolidinediones-and-ppar%C3%AE-in-bladder-cancer
#7
REVIEW
Melody Chiu, Lucien McBeth, Puneet Sindhwani, Terry D Hinds
The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPARγ, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively...
2017: PPAR Research
https://www.readbyqxmd.com/read/28239687/protein-phosphatase-5-contributes-to-the-overexpression-of-epigenetically-regulated-t-lymphocyte-genes-in-patients-with-lupus
#8
D Patel, G Gorelik, B Richardson
OBJECTIVE: Lupus develops when genetically predisposed people encounter certain drugs or environmental agents causing oxidative stress such as infections and sun exposure, and then typically follows a chronic relapsing course with flares triggered by the exogenous stressors. Current evidence indicates that these environmental agents can trigger lupus flares by inhibiting the replication of DNA methylation patterns during mitosis in CD4(+) T cells, altering the expression of genes suppressed by this mechanism that convert normal "helper" cells into auto reactive cells which promote lupus flares...
December 2016: Lupus (Los Angeles)
https://www.readbyqxmd.com/read/28129433/celastrol-ameliorates-cd-induced-neuronal-apoptosis-by-targeting-nox2-derived-ros-dependent-pp5-jnk-signaling-pathway
#9
Chong Xu, Xiaoxue Wang, Chenjian Gu, Hai Zhang, Ruijie Zhang, Xiaoqing Dong, Chunxiao Liu, Xiaoyu Hu, Xiang Ji, Shile Huang, Long Chen
Celastrol, a plant-derived triterpene, has neuroprotective benefit in the models of neurodegenerative disorders that are characterized by overproduction of reactive oxygen species (ROS). Recently, we have reported that cadmium (Cd) activates c-Jun N-terminal kinase (JNK) pathway leading to neuronal cell death by inducing ROS inactivation of protein phosphatase 5 (PP5), and celastrol prevents Cd-activated JNK pathway against neuronal apoptosis. Therefore, we hypothesized that celastrol could hinder Cd induction of ROS-dependent PP5-JNK signaling pathway from apoptosis in neuronal cells...
April 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28096467/mir-21-mediated-radioresistance-occurs-via-promoting-repair-of-dna-double-strand-breaks
#10
Baocheng Hu, Xiang Wang, Shuofeng Hu, Xiaomin Ying, Ping Wang, Xiangming Zhang, Jian Wang, Hongyan Wang, Ya Wang
miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28090608/elevated-expression-of-serine-threonine-phosphatase-type-5-correlates-with-malignant-proliferation-in-human-osteosarcoma
#11
Kun Han, Zhihua Gan, Shuchen Lin, Haiyan Hu, Zan Shen, Daliu Min
Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. However, the involvement of serine/threonine phosphatase type 5 (PP5) in osteosarcoma remains unclear. The aim of this study was to evaluate the functional role of PP5 in osteosarcoma cells. Firstly, we found that PP5 is widely expressed in several human osteosarcoma cell lines. Then we used lentivirus-delivered siRNA to silence PP5 expression in Saos-2 and U2OS cell lines. Knockdown of endogenous PP5 expression by shRNA-expressing lentivirus significantly decreased the viability and proliferation of the osteosarcoma cells...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27886809/small-mammal-utilization-by-middle-stone-age-humans-at-die-kelders-cave-1-and-pinnacle-point-site-5-6-western-cape-province-south-africa
#12
Aaron Armstrong
Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations...
December 2016: Journal of Human Evolution
https://www.readbyqxmd.com/read/27827901/structure-activity-relationship-studies-using-natural-and-synthetic-okadaic-acid-dinophysistoxin-toxins
#13
Michael J Twiner, Gregory J Doucette, Yucheng Pang, Chao Fang, Craig J Forsyth, Christopher O Miles
Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays...
November 4, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27784696/serine-threonine-phosphatases-and-aquaporin-2-regulation-in-renal-collecting-duct
#14
Sophia M LeMaire, Viswanathan Raghuram, Cameron R Grady, Christina M Pickering, Chung-Lin Chou, Ezigbobiara N Umejiego, Mark A Knepper
Phosphorylation of the aquaporin-2 (AQP2) water channel at four COOH-terminal serines plays a central role in the regulation of water permeability of the renal collecting duct. The level of phosphorylation at these sites is determined by a balance between phosphorylation by protein kinases and dephosphorylation by phosphatases. The phosphatases that dephosphorylate AQP2 have not been identified. Here, we use large-scale data integration techniques to identify serine-threonine phosphatases likely to interact with AQP2 in renal collecting duct principal cells...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27742828/cytokine-induced-glucocorticoid-resistance-from-eosinophil-activation-protein-phosphatase-5-modulation-of-glucocorticoid-receptor-phosphorylation-and-signaling
#15
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27687725/protein-phosphatase-pp5-controls-bone-mass-and-the-negative-effects-of-rosiglitazone-on-bone-through-reciprocal-regulation-of-ppar%C3%AE-peroxisome-proliferator-activated-receptor-%C3%AE-and-runx2-runt-related-transcription-factor-2
#16
Lance A Stechschulte, Chunxi Ge, Terry D Hinds, Edwin R Sanchez, Renny T Franceschi, Beata Lecka-Czernik
Peroxisome proliferator-activated receptor γ (PPARγ) and runt-related transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC) differentiation toward adipocytes and osteoblasts, respectively. Post-translational modifications of these factors determine their activities. Dephosphorylation of PPARγ at Ser-112 is required for its adipocytic activity, whereas phosphorylation of RUNX2 at serine 319 (Ser-319) promotes its osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting each serine...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27628691/an-ultra-high-throughput-screen-for-catalytic-inhibitors-of-serine-threonine-protein-phosphatases-types-1-and-5-pp1c-and-pp5c
#17
Mark Swingle, Claude-Henry Volmar, S Adrian Saldanha, Peter Chase, Christina Eberhart, Edward A Salter, Brandon D'Arcy, Chad E Schroeder, Jennifer E Golden, Andrzej Wierzbicki, Peter Hodder, Richard E Honkanen
Although there has been substantial success in the development of specific inhibitors for protein kinases, little progress has been made in the identification of specific inhibitors for their protein phosphatase counterparts. Inhibitors of PP1 and PP5 are desired as probes for research and to test their potential for drug development. We developed and miniaturized (1536-well plate format) nearly identical homogeneous, fluorescence intensity (FLINT) enzymatic assays to detect inhibitors of PP1 or PP5. The assays were used in an ultra-high-throughput screening (uHTS) campaign, testing >315,000 small-molecule compounds...
January 2017: SLAS Discovery
https://www.readbyqxmd.com/read/27600583/oxidative-stress-impairs-the-stimulatory-effect-of-s100-proteins-on-protein-phosphatase-5-activity
#18
Fuminori Yamaguchi, Mitsumasa Tsuchiya, Seiko Shimamoto, Tomohito Fujimoto, Hiroshi Tokumitsu, Masaaki Tokuda, Ryoji Kobayashi
Oxidative stress is the consequence of an imbalance between the production of harmful reactive oxygen species and the cellular antioxidant system for neutralization, and it activates multiple intracellular signaling pathways, including apoptosis signal-regulating kinase 1 (ASK1). Protein phosphatase 5 (PP5) is a serine/threonine phosphatase involved in oxidative stress responses. Previously, we reported that S100 proteins activate PP5 in a calcium-dependent manner. S100 proteins belong to a family of small EF-hand calcium-binding proteins involved in many processes such as cell proliferation, differentiation, apoptosis, and inflammation...
September 2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27565380/phosphorylated-tandembp-a-unique-protein-substrate-for-protein-phosphatase-assay
#19
Yasunori Sugiyama, Sho Yamashita, Yuuki Uezato, Yukako Senga, Syouichi Katayama, Naoki Goshima, Yasushi Shigeri, Noriyuki Sueyoshi, Isamu Kameshita
To analyze a variety of protein phosphatases, we developed phosphorylated TandeMBP (P-TandeMBP), in which two different mouse myelin basic protein isoforms were fused in tandem, as a protein phosphatase substrate. P-TandeMBP was prepared efficiently in four steps: (1) phosphorylation of TandeMBP by a protein kinase mixture (Ca(2+)/calmodulin-dependent protein kinase Iδ, casein kinase 1δ, and extracellular signal-regulated kinase 2); (2) precipitation of both P-TandeMBP and protein kinases to remove ATP, Pi, and ADP; (3) acid extraction of P-TandeMBP with HCl to remove protein kinases; and (4) neutralization of the solution that contains P-TandeMBP with Tris...
November 15, 2016: Analytical Biochemistry
https://www.readbyqxmd.com/read/27501780/protein-phosphatase-5-mediates-corticosteroid-insensitivity-in-airway-smooth-muscle-in-patients-with-severe-asthma
#20
L Chachi, M Abbasian, A Gavrila, A Alzahrani, O Tliba, P Bradding, A J Wardlaw, C Brightling, Y Amrani
BACKGROUND: The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. METHODS: Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR...
January 2017: Allergy
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