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https://www.readbyqxmd.com/read/28202662/biogenesis-and-activity-regulation-of-protein-phosphatase-1
#1
REVIEW
Iris Verbinnen, Monica Ferreira, Mathieu Bollen
Protein phosphatase 1 (PP1) is expressed in all eukaryotic cells and catalyzes a substantial fraction of phosphoserine/threonine dephosphorylation reactions. It forms stable complexes with PP1-interacting proteins (PIPs) that guide the phosphatase throughout its life cycle and control its fate and function. The diversity of PIPs is huge (≈200 in vertebrates), and most of them combine short linear motifs to form large and unique interaction interfaces with PP1. Many PIPs have separate domains for PP1 anchoring, PP1 regulation, substrate recruitment and subcellular targeting, which enable them to direct associated PP1 to a specific subset of substrates and mediate acute activity control...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28189088/identification-of-residues-within-the-african-swine-fever-virus-dp71l-protein-required-for-dephosphorylation-of-translation-initiation-factor-eif2%C3%AE-and-inhibiting-activation-of-pro-apoptotic-chop
#2
Claire Barber, Chris Netherton, Lynnette Goatley, Alice Moon, Steve Goodbourn, Linda Dixon
The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required...
February 8, 2017: Virology
https://www.readbyqxmd.com/read/28188792/recruitment-of-pp1-to-the-centrosomal-scaffold-protein-cep192
#3
Isha Nasa, Laura Trinkle-Mulcahy, P Douglas, Sibapriya Chaudhuri, S P Lees-Miller, Kyung S Lee, Greg B Moorhead
Centrosomal protein of 192 kDa (CEP192) is a scaffolding protein that recruits the mitotic protein kinases Aurora A and PLK1 to the centrosome. Here we demonstrate that CEP192 also recruits the type one protein phosphatase (PP1) via a highly conserved KHVTF docking motif. The threonine of the KHVTF motif is phosphorylated during mitosis and protein kinase inhibition studies suggest this to be a PLK1-dependent process.
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28176357/bri2-processing-and-its-neuritogenic-role-are-modulated-by-protein-phosphatase-1-complexing
#4
Filipa Martins, Joana B Serrano, T Müller, Odete A B da Cruz E Silva, Sandra Rebelo
BRI2 is a ubiquitously expressed type-II transmembrane phosphoprotein. BRI2 undergoes proteolytic processing into secreted fragments and during the maturation process it suffers post-translational modifications. Of particular relevance, BRI2 is a protein phosphatase 1 (PP1) interacting protein, where PP1 is able to dephosphorylate the former. Further, disruption of the BRI2:PP1 complex, using BRI2 PP1 binding motif mutants, leads to increased BRI2 phosphorylation levels. However, the physiological function of BRI2 remains elusive; although findings suggest a role in neurite outgrowth and neuronal differentiation...
February 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28163251/overexpression-of-carboxylesterase-contributes-to-the-attenuation-of-cyanotoxin-microcystin-lr-toxicity
#5
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...
February 3, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28152298/salubrinal-alleviates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-endoplasmic-reticulum-stress-pathway
#6
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Chunghee Cho, Do Han Kim
Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs)...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#7
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28134629/liguzinediol-enhances-the-inotropic-effect-of-rat-hearts-via-inhibition-of-protein-phosphatase-pp1-and-pp2a-activities
#8
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/28131631/ryanodine-receptor-modification-and-regulation-by-intracellular-ca-2-and-mg-2-in-healthy-and-failing-human-hearts
#9
K Walweel, P Molenaar, M S Imtiaz, A Denniss, C Dos Remedios, D F van Helden, A F Dulhunty, D R Laver, N A Beard
RATIONALE: Heart failure is a multimodal disorder, of which disrupted Ca(2+) homeostasis is a hallmark. Central to Ca(2+) homeostasis is the major cardiac Ca(2+) release channel - the ryanodine receptor (RyR2) - whose activity is influenced by associated proteins, covalent modification and by Ca(2+) and Mg(2+). That RyR2 is remodelled and its function disturbed in heart failure is well recognized, but poorly understood. OBJECTIVE: To assess Ca(2+) and Mg(2+) regulation of RyR2 from left ventricles of healthy, cystic fibrosis and failing hearts, and to correlate these functional changes with RyR2 modifications and remodelling...
January 25, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28131630/the-effect-of-pka-mediated-phosphorylation-of-ryanodine-receptor-on-sr-ca-2-leak-in-ventricular-myocytes
#10
Elisa Bovo, Sabine Huke, Lothar A Blatter, Aleksey V Zima
Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca(2+) release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca(2+)] and intra-SR [Ca(2+)]SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies...
January 25, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28126489/the-protein-serine-threonine-phosphatases-pp2a-pp1-and-calcineurin-a-triple-threat-in-the-regulation-of-the-neuronal-cytoskeleton
#11
REVIEW
Alexander Hoffman, Goce Taleski, Estelle Sontag
The microtubule, F-actin and neurofilament networks play a critical role in neuronal cell morphogenesis, polarity and synaptic plasticity. Significantly, the assembly/disassembly and stability of these cytoskeletal networks is crucially modulated by protein phosphorylation and dephosphorylation events. Herein, we aim to more closely examine the role played by three major neuronal Ser/Thr protein phosphatases, PP2A, PP1 and calcineurin, in the homeostasis of the neuronal cytoskeleton. There is strong evidence that these enzymes interact with and dephosphorylate a variety of cytoskeletal proteins, resulting in major regulation of neuronal cytoskeletal dynamics...
January 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28103229/protein-phosphatase-1-down-regulates-zyg-1-levels-to-limit-centriole-duplication
#12
Nina Peel, Jyoti Iyer, Anar Naik, Michael P Dougherty, Markus Decker, Kevin F O'Connell
In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2SZY-2 and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation of szy-2 or sds-22 can rescue the loss of centriole duplication associated with a zyg-1 hypomorphic allele...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28102742/the-nucleoporin-mel-28-elys-a-pp1-scaffold-during-m-phase-exit
#13
Neil Hattersley, Arshad Desai
No abstract text is available yet for this article.
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28091603/repo-man-pp1-regulates-heterochromatin-formation-in-interphase
#14
Inês J de Castro, James Budzak, Maria L Di Giacinto, Lorena Ligammari, Ezgi Gokhan, Christos Spanos, Daniela Moralli, Christine Richardson, Jose I de Las Heras, Silvia Salatino, Eric C Schirmer, Katharine S Ullman, Wendy A Bickmore, Catherine Green, Juri Rappsilber, Sarah Lamble, Martin W Goldberg, Veronica Vinciotti, Paola Vagnarelli
Repo-Man is a protein phosphatase 1 (PP1) targeting subunit that regulates mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 remains associated with chromatin but its function in interphase is not known. Here we show that Repo-Man, via Nup153, is enriched on condensed chromatin at the nuclear periphery and at the edge of the nucleopore basket. Repo-Man/PP1 regulates the formation of heterochromatin, dephosphorylates H3S28 and it is necessary and sufficient for heterochromatin protein 1 binding and H3K27me3 recruitment...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28077461/human-rif1-and-protein-phosphatase-1-stimulate-dna-replication-origin-licensing-but-suppress-origin-activation
#15
Shin-Ichiro Hiraga, Tony Ly, Javier Garzón, Zuzana Hořejší, Yoshi-Nobu Ohkubo, Akinori Endo, Chikashi Obuse, Simon J Boulton, Angus I Lamond, Anne D Donaldson
The human RIF1 protein controls DNA replication, but the molecular mechanism is largely unknown. Here, we demonstrate that human RIF1 negatively regulates DNA replication by forming a complex with protein phosphatase 1 (PP1) that limits phosphorylation-mediated activation of the MCM replicative helicase. We identify specific residues on four MCM helicase subunits that show hyperphosphorylation upon RIF1 depletion, with the regulatory N-terminal domain of MCM4 being particularly strongly affected. In addition to this role in limiting origin activation, we discover an unexpected new role for human RIF1-PP1 in mediating efficient origin licensing...
January 11, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28077320/serine-threonine-phosphatases-in-atrial-fibrillation
#16
Jordi Heijman, Shokoufeh Ghezelbash, Xander H T Wehrens, Dobromir Dobrev
Serine/threonine protein phosphatases control dephosphorylation of numerous cardiac proteins, including a variety of ion channels and calcium-handling proteins, thereby providing precise post-translational regulation of cardiac electrophysiology and function. Accordingly, dysfunction of this regulation can contribute to the initiation, maintenance and progression of cardiac arrhythmias. Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by electrical, autonomic, calcium-handling, contractile, and structural remodeling, which include, among other things, changes in the phosphorylation status of a wide range of proteins...
January 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28074910/myosin-phosphatase-and-rhoa-activated-kinase-modulate-arginine-methylation-by-the-regulation-of-protein-arginine-methyltransferase-5-in-hepatocellular-carcinoma-cells
#17
Adrienn Sipos, Judit Iván, Bálint Bécsi, Zsuzsanna Darula, István Tamás, Dániel Horváth, Katalin F Medzihradszky, Ferenc Erdődi, Beáta Lontay
Myosin phosphatase (MP) holoenzyme is a protein phosphatase-1 (PP1) type Ser/Thr specific enzyme that consists of a PP1 catalytic (PP1c) and a myosin phosphatase target subunit-1 (MYPT1). MYPT1 is an ubiquitously expressed isoform and it targets PP1c to its substrates. We identified the protein arginine methyltransferase 5 (PRMT5) enzyme of the methylosome complex as a MYPT1-binding protein uncovering the nuclear MYPT1-interactome of hepatocellular carcinoma cells. It is shown that PRMT5 is regulated by phosphorylation at Thr80 by RhoA-associated protein kinase and MP...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069132/molecular-regulation-of-the-spindle-assembly-checkpoint-by-kinases-and-phosphatases
#18
G Manic, F Corradi, A Sistigu, S Siteni, I Vitale
The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28062487/alcohol-drives-s-nitrosylation-and-redox-activation-of-protein-phosphatase-1-causing-bovine-airway-cilia-dysfunction
#19
Michael Earl Price, Jacqueline A Pavlik, Miao Liu, Shi-Jian Ding, Todd A Wyatt, Joseph H Sisson
Individuals with alcohol (ethanol) use disorders are at increased risk for lung infections in part due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated demembranated bovine cilia (axonemes) are capable of producing nitric oxide (∙NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of ∙NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosium cations or ⋅NO to thiolate or thiyl groups, respectively, of proteins forming S-nitrosothiols...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28044939/inhibition-of-tgf-%C3%AE-signaling-in-tumor-cells-by-small-molecule-src-family-kinase-inhibitors
#20
Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnerta, Hendrik Ungefroren
In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated shown that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
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