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https://www.readbyqxmd.com/read/28239848/protein-phosphatase-2a-pp2a-regulation-of-markers-of-extracellular-matrix-remodelling-in-hcc-cells-functional-consequences-for-tumour-invasion
#1
M P Ward, J P Spiers
BACKGROUND AND PURPOSE: A hallmark of tumour invasion is breakdown of the extracellular matrix as a consequence of dysregulation of the MMP system. While our understanding of how this is regulated by kinase signalling pathways is well established, its counter-regulation by protein phosphatases is less well known. Therefore, we investigated the effect of inhibition of protein phosphatases on markers of extracellular remodelling and how PP2A modulates MMP-9 abundance and function of Hep3B cells...
February 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28224476/protein-phosphatase-2a-a-double-faced-phosphatase-of-cellular-system-and-its-role-in-neurodegenerative-disorders
#2
REVIEW
Md Nematullah, M N Hoda, Farah Khan
Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, is a vitally important phosphatase for the cellular system. Structurally, it is constituted of three different subunits, namely catalytic subunit (PP2Ac), structural scaffold subunit (PP2A-A), and regulatory subunit (PP2A-B). All subunits have various isoforms, and catalytic and scaffold subunits are ubiquitously expressed, whereas regulatory subunits are more specific to tissue and cell type. It is the numerous possibilities of PP2A holoenzyme assembly with varying isoform components that make it possess a dual nature of activator or the inhibitory character in different signaling pathways, namely neural developmental pathways, Akt/protein kinase B pathway, NF-kB pathway, MAPK pathway, apoptosis pathway, and cell cycle progression to name a few...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28224044/mastl-is-essential-for-anaphase-entry-of-proliferating-primordial-germ-cells-and-establishment-of-female-germ-cells-in-mice
#3
Sanjiv Risal, Jingjing Zhang, Deepak Adhikari, Xiaoman Liu, Jingchen Shao, Mengwen Hu, Kiran Busayavalasa, Zhaowei Tu, Zijiang Chen, Philipp Kaldis, Kui Liu
In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28222497/correction-lapatinib-inhibits-cip2a-pp2a-p-akt-signaling-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#4
Chun-Yu Liu, Ming-Hung Hu, Chia-Jung Hsu, Chun-Teng Huang, Duen-Shian Wang, Wen-Chun Tsai, Yi-Ting Chen, Chia-Han Lee, Pei-Yi Chu, Chia-Chi Hsu, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
No abstract text is available yet for this article.
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208772/transcriptional-and-behavioral-responses-of-zebrafish-larvae-to-microcystin-lr-exposure
#5
Eleni Tzima, Iliana Serifi, Ioanna Tsikari, Ainhoa Alzualde, Ioannis Leonardos, Thomais Papamarcaki
Microcystins are cyclic heptapeptides that constitute a diverse group of toxins produced by cyanobacteria. One of the most toxic variants of this family is microcystin-LR (MCLR) which is a potent inhibitor of protein phosphatase 2A (PP2A) and induces cytoskeleton alterations. In this study, zebrafish larvae exposed to 500 μg/L of MCLR for four days exhibited a 40% reduction of PP2A activity compared to the controls, indicating early effects of the toxin. Gene expression profiling of the MCLR-exposed larvae using microarray analysis revealed that keratin 96 (krt96) was the most downregulated gene, consistent with the well-documented effects of MCLR on cytoskeleton structure...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202907/calpain-1-deletion-impairs-mglur-dependent-ltd-and-fear-memory-extinction
#6
Guoqi Zhu, Victor Briz, Jeff Seinfeld, Yan Liu, Xiaoning Bi, Michel Baudry
Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199842/the-mtor-and-pp2a-pathways-regulate-phd2-phosphorylation-to-fine-tune-hif1%C3%AE-levels-and-colorectal-cancer-cell-survival-under-hypoxia
#7
Giusy Di Conza, Sarah Trusso Cafarello, Stefan Loroch, Daniela Mennerich, Sofie Deschoemaeker, Mario Di Matteo, Manuel Ehling, Kris Gevaert, Hans Prenen, Rene Peiman Zahedi, Albert Sickmann, Thomas Kietzmann, Fabiola Moretti, Massimiliano Mazzone
Oxygen-dependent HIF1α hydroxylation and degradation are strictly controlled by PHD2. In hypoxia, HIF1α partly escapes degradation because of low oxygen availability. Here, we show that PHD2 is phosphorylated on serine 125 (S125) by the mechanistic target of rapamycin (mTOR) downstream kinase P70S6K and that this phosphorylation increases its ability to degrade HIF1α. mTOR blockade in hypoxia by REDD1 restrains P70S6K and unleashes PP2A phosphatase activity. Through its regulatory subunit B55α, PP2A directly dephosphorylates PHD2 on S125, resulting in a further reduction of PHD2 activity that ultimately boosts HIF1α accumulation...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28191283/active-%C3%AE-catenin-is-regulated-by-the-pten-pi3-kinase-pathway-a-role-for-protein-phosphatase-pp2a
#8
Amit Persad, Geetha Venkateswaran, Li Hao, Maria E Garcia, Jenny Yoon, Jaskiran Sidhu, Sujata Persad
Dysregulation of Wnt/β-catenin signaling has been associated with the development and progression of many cancers. The stability and subcellular localization of β-catenin, a dual functional protein that plays a role in intracellular adhesion and in regulating gene expression, is tightly regulated. However, little is known about the transcriptionally active form of β-catenin, Active Beta Catenin (ABC), that is unphosphorylated at serine 37 (Ser37) and threonine 41 (Thr41). Elucidating the mechanism by which β-catenin is activated to generate ABC is vital to the development of therapeutic strategies to block β-catenin signaling for cancer treatment...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28188886/propofol-inhibits-high-glucose-induced-pp2a-expression-in-human-umbilical-vein-endothelial-cells
#9
Qichao Wu, Yanjun Zhao, Wenming Duan, Yi Liu, Xiangyuan Chen, Minmin Zhu
Perioperative hyperglycemia is a common clinical metabolic disorder. Hyperglycemia could induce endothelial apoptosis, dysfunction and inflammation, resulting in endothelial injury. Propofol is a widely used anesthetic drug in clinical settings. Our previous studies indicated that propofol, via inhibiting high glucose-induced PP2A expression, attenuated high glucose-induced reactive oxygen species (ROS) accumulation, thus improving endothelial apoptosis, dysfunction and inflammation. However, the mechanisms by which propofol attenuated high glucose-induced PP2A expression is still obscure...
February 8, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28174209/oncoprotein-cip2a-is-stabilized-via-interaction-with-tumor-suppressor-pp2a-b56
#10
Jiao Wang, Juha Okkeri, Karolina Pavic, Zhizhi Wang, Otto Kauko, Tuuli Halonen, Grzegorz Sarek, Päivi M Ojala, Zihe Rao, Wenqing Xu, Jukka Westermarck
Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3...
February 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28167675/arpp-16-is-a-striatal-enriched-inhibitor-of-protein-phosphatase-2a-regulated-by-microtubule-associated-serine-threonine-kinase-3-mast-3-kinase
#11
Erika C Andrade, Veronica Musante, Atsuko Horiuchi, Hideo Matsuzaki, A Harrison Brody, Terence Wu, Paul Greengard, Jane R Taylor, Angus C Nairn
: ARPP-16 (cAMP-Regulated Phospho-Protein of molecular weight 16 kDa) is one of several small acid-soluble proteins highly expressed in medium spiny neurons (MSNs) of striatum that are phosphorylated in response to dopamine acting via D1 receptor/protein kinase A (PKA) signaling. We show here that ARPP-16 is also phosphorylated in vitro and in vivo by microtubule-associated serine/threonine kinase 3 (MAST3 kinase), an enzyme of previously unknown function that is enriched in striatum...
February 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28165500/flavonol-induced-changes-in-pin2-polarity-and-auxin-transport-in-the-arabidopsis-thaliana-rol1-2-mutant-require-phosphatase-activity
#12
Benjamin M Kuhn, Tomasz Nodzyński, Sanae Errafi, Rahel Bucher, Shibu Gupta, Bibek Aryal, Petre Dobrev, Laurent Bigler, Markus Geisler, Eva Zažímalová, Jiří Friml, Christoph Ringli
The phytohormone auxin is a major determinant and regulatory component important for plant development. Auxin transport between cells is mediated by a complex system of transporters such as AUX1/LAX, PIN, and ABCB proteins, and their localization and activity is thought to be influenced by phosphatases and kinases. Flavonols have been shown to alter auxin transport activity and changes in flavonol accumulation in the Arabidopsis thaliana rol1-2 mutant cause defects in auxin transport and seedling development...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163251/overexpression-of-carboxylesterase-contributes-to-the-attenuation-of-cyanotoxin-microcystin-lr-toxicity
#13
Shota Takumi, Tai Shimono, Satoshi Ikema, Yuki Hotta, Petros K Chigwechokha, Kazuhiro Shiozaki, Yasumasa Sugiyama, Mitsuru Hashimoto, Tatsuhiko Furukawa, Masaharu Komatsu
Microcystin-LR is a hepatotoxin produced by several cyanobacteria. Its toxicity is mainly due to a inhibition of protein phosphatase, PP1 and PP2A. Previously, we used a cell line stably expressing uptake transporter for microcystin-LR, OATP1B3 (HEK293-OATP1B3 cells). In this study, to determine whether overexpression of carboxylesterase (CES), which degrades ester-group and amide-group, attenuates the cytotoxicity of microcystin-LR, we generated the HEK293-OATP1B3/CES2 double-transfected cells. HEK293-OATP1B3/CES2 cells showed high hydrolysis activity of p-nitrophenyl acetate (PNPA), which is an authentic substrate for esterase...
April 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28161506/mathematical-modelling-unveils-the-essential-role-of-cellular-phosphatases-in-the-inhibition-of-raf-mek-erk-signalling-by-sorafenib-in-hepatocellular-carcinoma-cells
#14
Zuzana Saidak, Anne-Sophie Giacobbi, Christophe Louandre, Chloé Sauzay, Youcef Mammeri, Antoine Galmiche
The RAS-RAF-MEK-ERK cascade is a key oncogenic signal transduction pathway activated in many types of tumours in humans. Sorafenib, the medical treatment of reference against advanced stages of hepatocellular carcinoma (HCC), inhibits the RAF-MEK-ERK cascade in HCC cells. Based on previous studies suggesting that this cascade is an important target of sorafenib in HCC cells, we explored its regulation using mathematical modelling and ordinary differential equations. We analysed the dynamic regulation of the core components of the RAF-MEK-ERK cascade in three human HCC cell lines (Huh7, Hep3B and PLC/PRF5) with heterogeneous responses to sorafenib...
February 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28159925/mirna-1246-induces-pro-inflammatory-responses-in-mesenchymal-stem-stromal-cells-by-regulating-pka-and-pp2a
#15
Alexander Bott, Nese Erdem, Shalom Lerrer, Agnes Hotz-Wagenblatt, Christian Breunig, Khalid Abnaof, Angelika Wörner, Heike Wilhelm, Ewald Münstermann, Adit Ben-Baruch, Stefan Wiemann
The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155571/the-augmentation-of-bk-channel-activity-by-nitric-oxide-signaling-in-rat-cerebral-arteries-involves-co-localized-regulatory-elements
#16
Barry D Kyle, Ramesh C Mishra, Andrew P Braun
Large conductance, Ca(2+)-activated K(+) (BK) channels control cerebrovascular tone; however, the regulatory processes influencing these channels remain poorly understood. Here, we investigate the cellular mechanisms underlying the enhancement of BK current in rat cerebral arteries by nitric oxide (NO) signaling. In isolated cerebral myocytes, BK current magnitude was reversibly increased by sodium nitroprusside (SNP, 100 μM) and sensitive to the BK channel inhibitor, penitrem-A (100 nM). Fostriecin (30 nM), a protein phosphatase type 2A (PP2A) inhibitor, significantly prolonged the SNP-induced augmentation of BK current and a similar effect was produced by sildenafil (30 nM), a phosphodiesterase 5 (PDE5) inhibitor...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28137967/selenomethionine-mitigates-cognitive-decline-by-targeting-both-tau-hyperphosphorylation-and-autophagic-clearance-in-an-alzheimer-s-disease-mouse-model
#17
Zhong-Hao Zhang, Qiu-Yan Wu, Rui Zheng, Chen Chen, Yao Chen, Qiong Liu, Peter R Hoffmann, Jia-Zuan Ni, Guo-Li Song
: Tau pathology was recently identified as a key driver of disease progression and an attractive therapeutic target in Alzheimer's disease (AD). Selenomethionine (Se-Met), a major bioactive form of selenium (Se) in organisms with significant antioxidant capacity, reduced the levels of total tau and hyperphosphorylated tau and ameliorated cognitive deficits in younger triple transgenic AD (3xTg-AD) mice. Whether Se-Met has a similar effect on tau pathology and the specific mechanism of action in older 3xTg-AD mice remains unknown...
January 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28137908/the-pp2a-b56-phosphatase-opposes-cyclin-e-autocatalytic-degradation-via-site-specific-dephosphorylation
#18
Ryan J Davis, Jherek Swanger, Bridget T Hughes, Bruce E Clurman
Cyclin E, in conjunction with its catalytic partner cyclin-dependent kinase 2 (CDK2), regulates cell cycle progression as cells exit quiescence and enter S-phase. Multiple mechanisms control cyclin E periodicity during the cell cycle, including phosphorylation-dependent cyclin E ubiquitylation by the SCF(Fbw7) ubiquitin ligase. Serine 384 (S384) is the critical cyclin E phosphorylation site that stimulates Fbw7 binding and cyclin E ubiquitylation and degradation. Because S384 is autophosphorylated by bound CDK2, this presents a paradox as to how cyclin E can evade autocatalytically induced degradation in order to phosphorylate its other substrates...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28134629/liguzinediol-enhances-the-inotropic-effect-of-rat-hearts-via-inhibition-of-protein-phosphatase-pp1-and-pp2a-activities
#19
Sha Li, Huili Huang, Mengdan Zhang, Wei Wang, Shuyin Xue, Ying Gao, Ming Xie, Kesu Chen, Fuming Liu, Long Chen
It has been demonstrated that Liguzinediol (LZDO), a derivative of ligustrazine from ligusticum wallichii Franch, exerts positive inotropy in isolated rat heart mediated by the sarcoplasmic reticulum Ca-ATPase (SERCA2a). Here, we further explore the underlying mechanism of the positive inotropic effect of LZDO in rat hearts. In vivo and ex vivo rat heart experiments, biochemistry and Western blot techniques were used to analyze the rat heart contractility, SERCA2a activity, phospholamban (PLB) phosphorylation and protein phosphatase (PP1 and PP2A) activities in rat left ventricular myocytes, respectively...
January 27, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28132875/the-impact-of-cruciferous-vegetable-isothiocyanates-on-histone-acetylation-and-histone-phosphorylation-in-bladder-cancer
#20
Besma Abbaoui, Kelly H Telu, Christopher R Lucas, Jennifer M Thomas-Ahner, Steven J Schwartz, Steven K Clinton, Michael A Freitas, Amir Mortazavi
: Cruciferous vegetable intake is associated with reduced risk of bladder cancer, yet mechanisms remain unclear. Cruciferous vegetable isothiocyanates (ITCs), namely sulforaphane (SFN) and erucin (ECN), significantly inhibit histone deacetylase (HDAC) activity in human bladder cancer cells representing superficial to invasive biology (59-83% inhibition with 20μM, 48h treatment), and in bladder cancer xenografts (59±3% ECN inhibition). Individual HDACs inhibited by SFN and ECN include HDACs 1, 2, 4 and 6...
March 6, 2017: Journal of Proteomics
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