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Protein phosphatase 2a

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https://www.readbyqxmd.com/read/28634862/effect-of-gapt-extract-on-expression-of-tau-protein-and-its-phosphorylation-related-enzymes-in-hippocampal-neurons-of-appv717i-transgenic-mice
#1
Jing-Nian Ni, Jing Shi, Xue-Kai Zhang, Yi-Chang Yang, Xiao-Meng Liu, Ming-Qing Wei, Ting Li, Peng-Wen Wang, Jin-Zhou Tian, Yong-Yan Wang
OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg d)], the low, medium and high dosage of GAPT groups [0...
June 20, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28613156/reciprocal-regulation-of-arpp-16-by-pka-and-mast-3-kinases-provides-a-camp-regulated-switch-in-protein-phosphatase-2a-inhibition
#2
Veronica Musante, Lu Li, Jean Kanyo, Tukiet T Lam, Christopher M Colangelo, Shuk Kei Cheng, Harrison Brody, Paul Greengard, Nicolas Le Novère, Angus C Nairn
ARPP-16, ARPP-19, and ENSA are inhibitors of protein phosphatase PP2A. ARPP-19 and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. ARPP-16 is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The ARPP-16/19 proteins were discovered as substrates for PKA, but the function of PKA phosphorylation is unknown. We find that phosphorylation by PKA or MAST3 mutually suppresses the ability of the other kinase to act on ARPP-16...
June 14, 2017: ELife
https://www.readbyqxmd.com/read/28612433/musculin-inhibits-human-t-helper-17-cell-response-to-interleukin-2-by-controlling-stat5b-activity
#3
Veronica Santarlasci, Alessio Mazzoni, Manuela Capone, Maria Caterina Rossi, Laura Maggi, Gianni Montaini, Beatrice Rossettini, Rolando Cimaz, Matteo Ramazzotti, Giusi Barra, Raffaele De Palma, Enrico Maggi, Francesco Liotta, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
We recently demonstrated that human T helper (Th) 17 cells, unlike Th1 cells, do not proliferate in response to T-cell receptor stimulation, mainly because of their reduced capacity to produce and respond to IL-2. In this study we show that their lower responsiveness to IL-2 is due to the selective expression of Musculin (MSC), a member of the basic helix-loop-helix transcription factors. We show that MSC expression in human Th17 cells is retinoic acid orphan receptor (ROR)γt-dependent, and allows the up-regulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28603063/overexpression-of-phosphoprotein-phosphatase-2a-predicts-worse-prognosis-in-patients-with-breast-cancer-a-15-year-follow-up
#4
Po-Ming Chen, Pei-Yi Chu, Shiao-Lin Tung, Chun-Yu Liu, Yi-Fang Tsai, Yen-Shu Lin, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ta-Chung Chao, Ling-Ming Tseng
Breast cancer subtypes can be stratified by immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A)...
June 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28587927/the-%C3%AE-4-subunit-of-the-voltage-gated-calcium-channel-cacnb4-regulates-the-rate-of-cell-proliferation-in-chinese-hamster-ovary-cells
#5
Mohamad Rima, Marwa Daghsni, Stephan De Waard, Nathalie Gaborit, Ziad Fajloun, Michel Ronjat, Yasuo Mori, Juan L Brusés, Michel De Waard
The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β4) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities...
June 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28586756/inhibitors-of-the-pi3k-mtor-pathway-prevent-stat5-phosphorylation-in-jak2v617f-mutated-cells-through-pp2a-cip2a-axis
#6
Niccolò Bartalucci, Laura Calabresi, Manjola Balliu, Serena Martinelli, Maria Caterina Rossi, Jean Luc Villeval, Francesco Annunziato, Paola Guglielmelli, Alessandro M Vannucchi
Inhibition of the constitutively activated JAK/STAT pathway in JAK2V617F mutated cells by the JAK1/JAK2 inhibitor ruxolitinib resulted in clinical benefits in patients with myeloproliferative neoplasms. However, evidence of disease-modifying effects remains scanty; furthermore, some patients do not respond adequately to ruxolitinib, or have transient responses, thus novel treatment strategies are needed. Here we demonstrate that ruxolitinib causes incomplete inhibition of STAT5 in JAK2V617F mutated cells due to persistence of phosphorylated serine residues of STAT5b, that conversely are targeted by PI3K and mTORC1 inhibitors...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28585125/role-of-microtubule-associated-protein-tau-phosphorylation-in-alzheimer-s-disease
#7
REVIEW
Rong-Hong Ma, Yao Zhang, Xiao-Yue Hong, Jun-Fei Zhang, Jian-Zhi Wang, Gong-Ping Liu
As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer's disease (AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) are the most implicated...
June 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28577190/17%C3%AE-estradiol-and-or-estrogen-receptor-alpha-blocks-isoproterenol-induced-calcium-accumulation-and-hypertrophy-via-gsk3%C3%AE-pp2a-nfat3-anp-pathway
#8
Peiying Pai, Bharath Kumar Velmurugan, Chia-Hua Kuo, Chung-Yi Yen, Tsung-Jung Ho, Yueh-Min Lin, Yu-Feng Chen, Chao-Hung Lai, Cecilia Hsuan Day, Chih-Yang Huang
The present study was aimed to investigate the protective effects of 17β-estradiol (E2) and estrogen receptor α (ERα) on isoproterenol (ISO)-treated H9c2 cardiomyoblast cells. In the present study, we treated H9c2 cells with ISO, a β-adrenergic receptor agonist, to induce myocardiac hypertrophy. Pre-administration of E2 or ERα (induced by doxycycline) and E2 plus ERα significantly prevented ISO-induced increase of cell size and cytosolic calcium accumulation, accompanied with increased mRNA of atrial natriuretic peptide and brain natriuretic peptide...
June 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28560452/arctigenin-inhibits-triple-negative-breast-cancers-by-targeting-cip2a-to-reactivate-protein-phosphatase-2a
#9
Qiuyue Huang, Shanshan Qin, Xiaoning Yuan, Liang Zhang, Juanli Ji, Xuewen Liu, Wenjing Ma, Yunfei Zhang, Pengfei Liu, Zhiting Sun, Jingxuan Zhang, Ying Liu
We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers...
May 24, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28559983/feedback-between-e2f1-and-cip2a-regulated-by-human-papillomavirus-e7-in-cervical-cancer-implications-for-prognosis
#10
Xiao Wang, Peng Gao, Meng Wang, Jing Liu, Jiaxiang Lin, Shule Zhang, Yiwei Zhao, Jingwen Zhang, Wei Pan, Zeyu Sun, Feifei Sun, Weiming Zhao, Chenghao Guo, Qingwei Wang
Previously, we found that cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a key role in the malignant transformation of cervical cancer. Here, we further explore whether and how CIP2A is regulated by human papillomavirus E7 (HPV E7) and the prognostic value of CIP2A in cervical cancer. We demonstrated a positive feedback loop between the E2F transcription factor 1 (E2F1) and CIP2A at the transcription level in HeLa and SiHa cells by real-time PCR and western blot analysis. The feedback, regulated by HPV E7, was further confirmed by their sub-cellular co-expression seen on immunofluorescence and immunohistochemistry staining in vitro and in vivo...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28553304/reference-gene-selection-for-qrt-pcr-normalization-analysis-in-kenaf-hibiscus-cannabinus-l-under-abiotic-stress-and-hormonal-stimuli
#11
Xiaoping Niu, Meixia Chen, Xinyu Huang, Huihuang Chen, Aifen Tao, Jiantang Xu, Jianmin Qi
Kenaf (Hibiscus cannabinus L.), an environmental friendly and economic fiber crop, has a certain tolerance to abiotic stresses. Identification of reliable reference genes for transcript normalization of stress responsive genes expression by quantitative real-time PCR (qRT-PCR) is important for exploring the molecular mechanisms of plants response to abiotic stresses. In this study, nine candidate reference genes were cloned, and their expression stabilities were assessed in 132 abiotic stress and hormonal stimuli samples of kenaf using geNorm, NormFinder, and BestKeeper algorithms...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28548306/zanthoxylum-avicennae-extract-enhances-gsk-3%C3%AE-to-attenuate-%C3%AE-catenin-via-phosphatase-2a-to-block-metastatic-effects-of-ha22t-cells-and-hepatocellular-carcinoma-xenografted-nude-mice
#12
Hsi-Chin Wu, Ing-Shiow Lay, Marthandam Asokan Shibu, Tsung-Jung Ho, Shiu-Min Cheng, Chih-Hao Lin, Tran Duc Dung, Long-Bin Jeng, Vijaya Padma Viswanadha, Chih-Yang Huang
Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28546021/sodium-butyrate-improved-intestinal-immune-function-associated-with-nf-%C3%AE%C2%BAb-and-p38mapk-signalling-pathways-in-young-grass-carp-ctenopharyngodon-idella
#13
Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Fei Xie, Lin Feng
The present study evaluated the effect of dietary sodium butyrate (SB) supplementation on the growth and immune function in the proximal intestine (PI), middle intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg(-1) diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg(-1) diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28543283/targeting-pp2a-and-proteasome-activity-ameliorates-features-of-allergic-airway-disease-in-mice
#14
P M Nair, M R Starkey, T J Haw, G Liu, J C Horvat, J C Morris, N M Verrills, A R Clark, A J Ammit, P M Hansbro
BACKGROUND: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD...
May 24, 2017: Allergy
https://www.readbyqxmd.com/read/28534965/cucurbitacin%C3%A2-b-induces-autophagy-and-apoptosis-by-suppressing-cip2a-pp2a-mtorc1-signaling-axis-in-human-cisplatin-resistant-gastric-cancer-cells
#15
Xuewen Liu, Chao Duan, Juanli Ji, Te Zhang, Xiaoning Yuan, Yunfei Zhang, Wenjing Ma, Jingyuan Yang, Linsen Yang, Zhiguo Jiang, Huiliang Yu, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28526910/expression-and-regulation-of-type-2a-protein-phosphatases-and-alpha4-signalling-in-cardiac-health-and-hypertrophy
#16
Olga Eleftheriadou, Andrii Boguslavskyi, Michael R Longman, Jonathan Cowan, Asvi Francois, Richard J Heads, Brian E Wadzinski, Ali Ryan, Michael J Shattock, Andrew K Snabaitis
Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C)...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28526544/interleukin-18-gene-deletion-protects-against-sepsis-induced-cardiac-dysfunction-by-inhibiting-pp2a-activity
#17
Yoshitaka Okuhara, Shunichi Yokoe, Toshihiro Iwasaku, Akiyo Eguchi, Koichi Nishimura, Wen Li, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Michio Asahi, Haruki Okamura, Tohru Masuyama, Shinichi Hirotani
BACKGROUND: Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. METHODS AND RESULTS: Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS...
May 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28521777/cip2a-mediates-fibronectin-induced-bladder-cancer-cell-proliferation-by-stabilizing-%C3%AE-catenin
#18
Fengbin Gao, Tianyuan Xu, Xianjin Wang, Shan Zhong, Shanwen Chen, Minguang Zhang, Xiaohua Zhang, Yifan Shen, Xiaojing Wang, Chen Xu, Zhoujun Shen
BACKGROUND: Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. METHODS: The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients...
May 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28516459/pp2a-deactivation-is-a-common-event-in-oral-cancer-and-reactivation-by-fty720-shows-promising-therapeutic-potential
#19
Bharath K Velmurugan, Chien-Hung Lee, Shang-Lun Chiang, Chun-Hung Hua, Mei-Chung Chen, Shu-Hui Lin, Kun-Tu Yeh, Ying-Chin Ko
Protein phosphatase 2A (PP2A) is a tumor suppressor gene, that has been frequently deactivated in many types of cancer. However, its molecular and clinical relevance in oral squamous cell carcinoma (OSCC) remain unclear. Here we show that, PP2A deactivation is a common event in oral cancer cells and hyperphosphorylation in its tyrosine-307 (Y307) residue contributes to PP2A deactivation. PP2A restoration by FTY720 treatment reduced cell growth and decreased GSK-3β phosphorylation without significantly altering other PP2A targets...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28504652/a-smap-in-the-face-for-cancer
#20
Shirish Shenolikar
Observed deficits in protein phosphatase 2A (PP2A) function in a variety of human cancers have stimulated drug discovery efforts aimed at restoring PP2A function to inhibit tumor growth. Work published by Sangodkar et al. in this issue of the JCI describes the characterization of orally available small molecule activators of PP2A (SMAPs). These SMAPs attenuated mitogenic signaling and triggered apoptosis in KRAS-mutant lung cancer cells and inhibited tumor growth in murine models. Tumors with mutations in the SMAP-binding site of the PP2A A subunit displayed resistance to SMAPs...
June 1, 2017: Journal of Clinical Investigation
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