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phosphatase signalling

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https://www.readbyqxmd.com/read/28916342/pp2a-regulates-signaling-through-hormonal-receptors-in-breast-cancer-with-important-therapeutic-implications
#1
REVIEW
Ion Cristóbal, Blanca Torrejón, Javier Martínez-Useros, Juan Madoz-Gurpide, Federico Rojo, Jesús García-Foncillas
The functional inhibition of protein phosphatase 2A (PP2A) has emerged in the last years as a common alteration in breast cancer that determines poor outcome and contributes to disease progression and aggressiveness. Furthermore, expression of estrogen receptor (ER) is a high relevant molecular event with key therapeutic implications in breast cancer, and androgen receptor (AR) signaling is involved in the pathogenesis of breast cancer and represents a novel target with crescent importance in this disease. In this review, we summarize the role of the tumor suppressor PP2A in modulating ER and AR signaling in breast cancer, the molecular mechanisms involved, and its biological and therapeutic impact...
September 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#2
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
September 5, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28915803/tartrate-resistant-acid-phosphatase-trap-acp5-promotes-metastasis-related-properties-via-tgf%C3%AE-2-t%C3%AE-r-and-cd44-in-mda-mb-231-breast-cancer-cells
#3
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M Orre, Rui M M Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. METHODS: MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28915331/dual-specificity-phosphatase-5-substrate-interaction-a-mechanistic-perspective
#4
Raman G Kutty, Marat R Talipov, Robert D Bongard, Rachel A Jones Lipinski, Noreena L Sweeney, Daniel S Sem, Rajendra Rathore, Ramani Ramchandran
The mammalian genome contains approximately 200 phosphatases that are responsible for catalytically removing phosphate groups from proteins. In this review, we discuss dual specificity phosphatase 5 (DUSP5). DUSP5 belongs to the dual specificity phosphatase (DUSP) family, so named after the family members' abilities to remove phosphate groups from serine/threonine and tyrosine residues. We provide a comparison of DUSP5's structure to other DUSPs and, using molecular modeling studies, provide an explanation for DUSP5's mechanistic interaction and specificity toward phospho-extracellular regulated kinase, its only known substrate...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28913955/controlled-jagged1-delivery-induces-human-embryonic-palate-mesenchymal-cells-to-form-osteoblasts
#5
Jean De La Croix Ndong, Stephenson Yvonne, Michael E Davis, Andrés J García, Steven Goudy
Osteoblast commitment and differentiation are controlled by multiple growth factors including members of the Notch signaling pathway. JAGGED1 is a cell surface ligand of the Notch pathway that is necessary for murine bone formation. The delivery of JAGGED1 to induce bone formation is complicated by its need to be presented in a bound form to allow for proper Notch receptor signaling. In this study we investigate whether the sustained release of JAGGED1 stimulates human mesenchymal cells to commit to osteoblast cell fate using polyethylene glycol malemeide (PEG-MAL) hydrogel delivery system...
September 15, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28913664/supplementation-of-enzyme-treated-soy-protein-saves-dietary-protein-and-promotes-digestive-and-absorptive-ability-referring-to-tor-signaling-in-juvenile-fish
#6
Weiwei Xiao, Weidan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Yongan Zhang, Xiaoqiu Zhou
This study was conducted to evaluate the effect of enzyme-treated soy protein (ETSP) supplementation in the low-protein diet on growth performance, digestive and absorptive capacities, and related signaling molecules' gene expressions in juvenile Jian carp. The results showed that percent weight gain (PWG), specific growth rate (SGR), and feed intake (FI) were decreased by reducing dietary protein from 34 to 32% (P < 0.05). Supplying low-protein diet with optimal ETSP increased previously mentioned indices of juvenile Jian carp (P < 0...
September 14, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28912580/ptprj-inhibits-leptin-signaling-and-induction-of-ptprj-in-the-hypothalamus-is-a-cause-of-the-development-of-leptin-resistance
#7
Takafumi Shintani, Satoru Higashi, Ryoko Suzuki, Yasushi Takeuchi, Reina Ikaga, Tomomi Yamazaki, Kenta Kobayashi, Masaharu Noda
Leptin signaling in the hypothalamus plays a crucial role in the regulation of body weight. Leptin resistance, in which leptin signaling is disrupted, is a major obstacle to the improvement of obesity. We herein demonstrated that protein tyrosine phosphatase receptor type J (Ptprj) is expressed in hypothalamic neurons together with leptin receptors, and that PTPRJ negatively regulates leptin signaling by inhibiting the activation of JAK2, the primary tyrosine kinase in leptin signaling, through the dephosphorylation of Y813 and Y868 in JAK2 autophosphorylation sites...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912526/mpzl1-forms-a-signalling-complex-with-grb2-adaptor-and-ptpn11-phosphatase-in-her2-positive-breast-cancer-cells
#8
Alice Beigbeder, François J M Chartier, Nicolas Bisson
HER2/ErbB2 is overexpressed in a significant fraction of breast tumours and is associated with a poor prognosis. The adaptor protein GRB2 interacts directly with activated HER2 and is sufficient to transmit oncogenic signals. However, the consequence of HER2 activation on global GRB2 signalling networks is poorly characterized. We performed GRB2 affinity purification combined with mass spectrometry analysis of associated proteins in a HER2+ breast cancer model to delineate GRB2-nucleated protein interaction networks...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911943/heterozygous-deletion-of-akt1-rescues-cardiac-contractility-but-not-hypertrophy-in-a-mouse-model-of-noonan-syndrome-with-multiple-lentigines
#9
Rajika Roy, Maike Krenz
Noonan Syndrome with Multiple Lentigines (NSML) is associated with congenital heart disease in form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Genetically, NSML is primarily caused by mutations in the non-receptor protein tyrosine phosphatase SHP2. Importantly, certain SHP2 mutations such as Q510E can cause a particularly severe form of HCM with heart failure in infancy. Due to lack of insight into the underlying pathomechanisms, an effective custom-tailored therapy to prevent heart failure in these patients has not yet been found...
September 11, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28911860/glucose-elicits-serine-threonine-kinase-vrk1-to-phosphorylate-nuclear-pregnane-x-receptor-as-a-novel-hepatic-gluconeogenic-signal
#10
Saki Gotoh, Yuu Miyauchi, Rick Moore, Masahiko Negishi
Low glucose stimulated phosphorylation of pregnane X receptor (PXR) at Ser(350) in correlation with an increased gluconeogenesis in human hepatoma-derived HepG2 cells. Only glucose, but neither insulin nor glucagon, stimulated this phosphorylation. Here, serine/threonine kinase, vaccinia related kinase 1 (VRK1)-mediated phosphorylation of PXR is now defined as this glucose-elicited novel signal. In low glucose conditions, VRK1 directly phosphorylates PXR at Ser(350), enabling PO3-PXR to scaffold protein phosphatase PP2Cα...
September 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28910982/exosomes-containing-mir-21-transfer-the-characteristic-of-cisplatin-resistance-by-targeting-pten-and-pdcd4-in-oral-squamous-cell-carcinoma
#11
Tao Liu, Gang Chen, Dawei Sun, Minghui Lei, Yongqiang Li, Changming Zhou, Xiaodong Li, Wei Xue, Hong Wang, Chunjun Liu, Jiang Xu
Resistance to chemotherapy remains a major obstacle for the effective treatment of oral squamous cell carcinoma (OSCC). Evidence for the involvement of exosomes as important regulators of cisplatin chemoresistance in OSCC is still poorly understood. Our objective of this study was to explore the roles for exosomes in modulating key cellular pathways mediating response to chemotherapy. We first developed the cisplatin-resistant cell lines (HSC-3-R and SCC-9-R) and found that the conditioned media from cisplatin-resistant OSCC cells enhanced the chemoresistance of parental OSCC cell...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28910818/protein-expression-of-programmed-death-1-ligand-1-and-her2-in-gastric-carcinoma
#12
Eiji Oki, Shinji Okano, Hiroshi Saeki, Yuichiro Umemoto, Koji Teraishi, Yu Nakaji, Koji Ando, Yoko Zaitsu, Nami Yamashita, Masahiko Sugiyama, Yuichiro Nakashima, Kippei Ohgaki, Yoshinao Oda, Yoshihiko Maehara
OBJECTIVES: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. MATERIALS AND METHODS: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients...
September 15, 2017: Oncology
https://www.readbyqxmd.com/read/28910386/dusp5-and-dusp6-two-erk-specific-phosphatases-are-markers-of-a-higher-mapk-signaling-activation-in-braf-mutated-thyroid-cancers
#13
Camille Buffet, Karine Hecale-Perlemoine, Léopoldine Bricaire, Florent Dumont, Camille Baudry, Frédérique Tissier, Jérôme Bertherat, Beatrix Cochand-Priollet, Marie-Laure Raffin-Sanson, Françoise Cormier, Lionel Groussin
BACKGROUND: Molecular alterations of the MAPK pathway are frequently observed in papillary thyroid carcinomas (PTCs). It leads to a constitutive activation of the signalling pathway through an increase in MEK and ERK phosphorylation. ERK is negatively feedback-regulated by Dual Specificity Phosphatases (DUSPs), especially two ERK-specific DUSPs, DUSP5 (nuclear) and DUSP6 (cytosolic). These negative MAPK regulators may play a role in thyroid carcinogenesis. METHODS: MAPK pathway activation was analyzed in 11 human thyroid cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28910136/nrp1-accelerates-odontoblast-differentiation-of-dental-pulp-stem-cells-through-classical-wnt-%C3%AE-catenin-signaling
#14
Yihua Song, Xiaojuan Liu, Xingmei Feng, Zhifeng Gu, Yongchun Gu, Min Lian, Jingwen Xiao, Peipei Cao, Ke Zheng, Xiaobing Gu, Dongping Li, Ping He, Chenfei Wang
Neuropilin-1 (NRP1) is one of the members of neuropilin family. It can combine with disparate ligands involved in regulating cell proliferation, apoptosis, and differentiation. The binding of NRP1 to Sema3A stimulates osteoblast differentiation through the classical Wnt/β-catenin pathway. However, the functions of NRP1 in dental pulp stem cells (DPSCs) are not clear. The aim of our study was to investigate how NRP1 controlled odontoblast differentiation in DPSCs and clarified the underlying mechanisms. NRP1 expression was increased in time-dependent manner along with cell odontoblast differentiation...
September 14, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28906490/popx2-phosphatase-regulates-apoptosis-through-the-tak1-ikk-nf-%C3%AE%C2%BAb-pathway
#15
Ting Weng, Cheng-Gee Koh
Chemoresistance is one of the leading causes that contributes to tumor relapse and poor patient outcome after several rounds of drug therapy. The causes of chemoresistance are multi-factorial. Ultimately, it is the balance of pro- and anti-apoptotic activities in the cells. We have previously reported links between POPX2 serine/threonine phosphatase with cell motility and invasiveness of breast cancer cells. Here, we show that POPX2 plays a role in the regulation of apoptosis. The effect of POPX2 on apoptosis centers on the inactivation of TGF-β activated kinase (TAK1)...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28903340/multi-modality-imaging-monitored-creation-of-rat-orthotopic-pancreatic-head-cancer-with-obstructive-jaundice
#16
Zhibin Bai, Yaoping Shi, Jianfeng Wang, Longhua Qiu, Gaojun Teng, Feng Zhang, Xiaoming Yang
PURPOSE: To investigate the feasibility of using multi-modality imaging to monitor the creation of rat models with orthotopic pancreatic head cancer with obstructive jaundice. RESULTS: 27 of 52 rats (51.92%) developed pancreatic head cancer. The tumor formation rate was significantly higher in the animal group receiving bioluminescent tumor, compared to the group receiving non-bioluminescent donor tumors [78.1% (25/32 rats) vs 10.0% (2/20 rats), P = 0.0001]. Both ultrasound imaging and MRI clearly characterized the orthotopic tumors...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903318/myc-dependent-recruitment-of-runx1-and-gata2-on-the-set-oncogene-promoter-enhances-pp2a-inactivation-in-acute-myeloid-leukemia
#17
Raffaella Pippa, Ana Dominguez, Raquel Malumbres, Akinori Endo, Elena Arriazu, Nerea Marcotegui, Elizabeth Guruceaga, María D Odero
The SET (I2PP2A) oncoprotein is a potent inhibitor of protein phosphatase 2A (PP2A) that regulates many cell processes and important signaling pathways. Despite the importance of SET overexpression and its prognostic impact in both hematologic and solid tumors, little is known about the mechanisms involved in its transcriptional regulation. In this report, we define the minimal promoter region of the SET gene, and identify a novel multi-protein transcription complex, composed of MYC, SP1, RUNX1 and GATA2, which activates SET expression in AML...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902714/altered-subcellular-localization-of-fragile-x-mental-retardation-signaling-partners-and-targets-in-superior-frontal-cortex-of-individuals-with-schizophrenia
#18
S Hossein Fatemi, Timothy D Folsom, Paul D Thuras
Schizophrenia is a severe, debilitating, neurodevelopmental disorder that affects 1% of the world's population. Recent findings from our laboratory have identified reduced levels of fragile X mental retardation protein (FMRP) and several downstream FMRP targets in superior frontal cortex of individuals with schizophrenia. We hypothesized that altered subcellular expression of FMRP and its signaling partners may explain these changes. In the current study we employed subcellular fractionation and western blotting to determine levels of FMRP, phosphorylated-FMRP as well as selected signaling partners [protein phosphatase 2A catalytic subunit (PP2AC), p70 S6 kinase (p70 S6K), and amyloid-β A4 precursor protein (APP)] in the total homogenate, nuclear, and rough endoplasmic reticulum fractions in superior frontal cortex of individuals with schizophrenia versus controls (N=12/group)...
September 11, 2017: Neuroreport
https://www.readbyqxmd.com/read/28902166/critical-roles-of-dual-specificity-phosphatases-in-neuronal-proteostasis-and-neurological-diseases
#19
REVIEW
Noopur Bhore, Bo-Jeng Wang, Yun-Wen Chen, Yung-Feng Liao
Protein homeostasis or proteostasis is a fundamental cellular property that encompasses the dynamic balancing of processes in the proteostasis network (PN). Such processes include protein synthesis, folding, and degradation in both non-stressed and stressful conditions. The role of the PN in neurodegenerative disease is well-documented, where it is known to respond to changes in protein folding states or toxic gain-of-function protein aggregation. Dual-specificity phosphatases have recently emerged as important participants in maintaining balance within the PN, acting through modulation of cellular signaling pathways that are involved in neurodegeneration...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28901902/simian-varicella-virus-inhibits-the-interferon-gamma-signalling-pathway
#20
Werner J D Ouwendijk, Suzanne van Veen, Ravi Mahalingam, Georges M G M Verjans
The alphaherpesvirus simian varicella virus (SVV) causes varicella and zoster in nonhuman primates. Herpesviruses evolved elaborate mechanisms to escape host immunity, but the immune evasion strategies employed by SVV remain ill-defined. We analysed whether SVV impairs the cellular response to key antiviral cytokine interferon-γ (IFNγ). SVV infection inhibited the expression of IFNγ-induced genes like C-X-C motif chemokine 10 and interferon regulatory factor 1. Phosphorylation and nuclear translocation of the signal transducer and activator of transcription 1 (STAT1) was blocked in SVV-infected cells, which did not involve cellular and viral phosphatases...
September 13, 2017: Journal of General Virology
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