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https://www.readbyqxmd.com/read/27898395/corrigendum-quantitative-proteomic-analysis-of-purified-yeast-kinetochores-identifies-a-pp1-regulatory-subunit
#1
Bungo Akiyoshi, Christian R Nelson, Jeffrey A Ranish, Sue Biggins
No abstract text is available yet for this article.
October 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27890480/chemerin-induced-arterial-contraction-is-gi-and-calcium-dependent
#2
David J Ferland, Emma S Darios, Richard R Neubig, Benita Sjögren, Nguyen Truong, Rosa Torres, Thomas S Dexheimer, Janice M Thompson, Stephanie W Watts
Chemerin is an adipokine associated with increased blood pressure, and may link obesity with hypertension. We tested the hypothesis that chemerin-induced contraction of the vasculature occurs via calcium flux in smooth muscle cells. Isometric contraction of rat aortic rings was performed in parallel with calcium kinetics of rat aortic smooth muscle cells to assess the possible signaling pathway. Chemerin-9 (nonapeptide of the chemerin S(157) isoform) caused a concentration-dependent contraction of isolated aorta (EC50 100nM) and elicited a concentration-dependent intracellular calcium response (EC50 10nM)...
November 24, 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27881952/tissue-type-plasminogen-activator-tpa-modulates-the-postsynaptic-response-of-cerebral-cortical-neurons-to-the-presynaptic-release-of-glutamate
#3
Valerie Jeanneret, Fang Wu, Paola Merino, Enrique Torre, Ariel Diaz, Lihong Cheng, Manuel Yepes
Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing synaptic vesicles. Here we used electron microscopy, proteomics, quantitative phosphoproteomics, biochemical analyses with extracts of the postsynaptic density (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal tPA to study whether the presynaptic release of tPA also has an effect on the postsynaptic terminal...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27872653/the-zuo-jin-wan-formula-induces-mitochondrial-apoptosis-of-cisplatin-resistant-gastric-cancer-cells-via-cofilin-1
#4
Qing-Feng Tang, Jian Sun, Hui Yu, Xiao-Jing Shi, Rong Lv, Hong-Chang Wei, Pei-Hao Yin
Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy. Here we found that phosphorylated cofilin-1 (p-cofilin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines (SGC7901 and BGC823), and that DDP induced the dephosphorylation of p-cofilin-1 in both parent lines but not in the DDP-resistant lines...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27872270/hiv-glycoprotein-gp120-impairs-fast-axonal-transport-by-activating-tak1-signaling-pathways
#5
Sarah H Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T Brady
Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment...
December 2016: ASN Neuro
https://www.readbyqxmd.com/read/27871951/regulation-of-merlin-by-protein-phosphatase-1-timap-and-ebp50-in-endothelial-cells
#6
Anita Boratkó, Margit Péter, Csilla Csortos
Merlin (moesin-ezrin-radixin like protein), the product of neurofibromatosis type 2 gene, was primarily recognized as a tumor suppressor, but it also functions as a membrane-cytoskeletal linker and regulator of multiple signaling pathways. The activity and localization of merlin is regulated by head to tail folding that is controlled by phosphorylation of the Ser518 side chain. Merlin localizes in the nucleus when the Ser518 side chain is not phosphorylated, while the phosphorylated form is present in the cytoplasm and the plasma membrane...
November 18, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27856640/g-protein-coupled-receptors-gpcrs-that-signal-via-protein-kinase-a-pka-cross-talk-at-insulin-receptor-substrate-1-irs1-to-activate-the-pi3k-akt-pathway
#7
Nathan C Law, Morris F White, Mary E Hunzicker-Dunn
GPCRs (G protein-coupled receptors)2 activate PI3K/AKT (phosphatidylinositol-3 kinase/v-AKT thymoma viral oncoprotein) to regulate many cellular functions that promote cell survival, proliferation, and growth. However, the mechanism by which GPCRs activate PI3K/AKT remains poorly understood. We used ovarian preantral granulosa cells (GCs) to elucidate the mechanism by which the GPCR agonist FSH (follicle-stimulating hormone) via PKA (protein kinase A) activates the PI3K/AKT cascade. IGF1 (insulin-like growth factor 1) is secreted in an autocrine/paracrine manner by GCs and activates the IGF1R (IGF1 receptor), but in the absence of FSH fails to stimulate YXXM phosphorylation of IRS1 (insulin receptor substrate 1) required for PI3K/AKT activation...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27827901/structure-activity-relationship-studies-using-natural-and-synthetic-okadaic-acid-dinophysistoxin-toxins
#8
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/27820830/budding-yeast-rif1-controls-genome-integrity-by-inhibiting-rdna-replication
#9
Maksym Shyian, Stefano Mattarocci, Benjamin Albert, Lukas Hafner, Aleksandra Lezaja, Michael Costanzo, Charlie Boone, David Shore
The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc7 on rDNA replication is similar to that of the Sir2 deacetylase, and the two would appear to act in the same pathway, since the rif1Δ sir2Δ double mutant shows no further increase in rDNA replication...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27808115/multi-phasic-bi-directional-chemotactic-responses-of-the-growth-cone
#10
Honda Naoki, Makoto Nishiyama, Kazunobu Togashi, Yasunobu Igarashi, Kyonsoo Hong, Shin Ishii
The nerve growth cone is bi-directionally attracted and repelled by the same cue molecules depending on the situations, while other non-neural chemotactic cells usually show uni-directional attraction or repulsion toward their specific cue molecules. However, how the growth cone differs from other non-neural cells remains unclear. Toward this question, we developed a theory for describing chemotactic response based on a mathematical model of intracellular signaling of activator and inhibitor. Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807175/ablation-of-perk-in-schwann-cells-improves-myelination-in-the-s63del-charcot-marie-tooth-1b-mouse
#11
Mariapaola Sidoli, Nicolò Musner, Nicholas Silvestri, Daniela Ungaro, Maurizio D'Antonio, Douglas R Cavener, M Laura Feltri, Lawrence Wrabetz
: In factory cells, the accumulation of misfolded protein provokes the unfolded protein response (UPR). For example, deletion of serine 63 (S63del) in myelin protein zero (P0) induces P0 accumulation in the endoplasmic reticulum (ER) of Schwann cells and a persistent UPR associated with Charcot-Marie-Tooth 1B (CMT1B) demyelinating peripheral neuropathy in human and mouse. PERK (protein kinase RNA-like ER kinase) is the ER stress sensor that attenuates global translation by phosphorylating eIF2α...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27802161/elys-regulates-the-localization-of-lbr-by-modulating-its-phosphorylation-state
#12
Yasuhiro Mimura, Masatoshi Takagi, Michaela Clever, Naoko Imamoto
Lamin B receptor (LBR), an inner nuclear membrane (INM) protein, contributes to the functional integrity of the nucleus by tethering heterochromatin to the nuclear envelope. We have previously reported that the depletion of embryonic large molecule derived from yolk sac (ELYS; also known as AHCTF1), a component of the nuclear pore complex, from cells perturbs the localization of LBR to the INM, but little is known about the underlying molecular mechanism. In this study, we found that the depletion of ELYS promoted LBR phosphorylation at the residues known to be phosphorylated by cyclin-dependent kinase (CDK) and serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2, respectively)...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27784696/serine-threonine-phosphatases-and-aquaporin-2-regulation-in-renal-collecting-duct
#13
Sophia 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...
October 26, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27759153/the-master-greatwall-kinase-a-critical-regulator-of-mitosis-and-meiosis
#14
Suzanne Vigneron, Perle Robert, Khaled Hached, Lena Sundermann, Sophie Charrasse, Jean-Claude Labbé, Anna Castro, Thierry Lorca
Entry into mitosis requires the coordinated activation of various protein kinases and phosphatases that together activate sequential signaling pathways allowing entry, progression and exit of mitosis. The limiting step is thought to be the activation of the mitotic Cdk1-cyclin B kinase. However, this model has recently evolved with new data showing that in addition to the Cdk1-cyclin B complex, Greatwall (Gwl) kinase is also required to enter into and maintain mitosis. This new concept proposes that entry into mitosis is now based on the combined activation of both kinases Cdk1-cyclin B and Gwl, the former promoting massive phosphorylation of mitotic substrates and the latter inhibiting PP2A-B55 phosphatase responsible for dephosphorylation of these substrates...
2016: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/27757582/regulation-of-gap-junction-conductance-by-calcineurin-through-cx43-phosphorylation-implications-for-action-potential-conduction
#15
Rita I Jabr, Fiona S Hatch, Samantha C Salvage, Alejandro Orlowski, Paul D Lampe, Christopher H Fry
Cardiac arrhythmias are associated with raised intracellular [Ca(2+)] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca(2+)-dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27729423/maternal-memi-promotes-female-meiosis-ii-in-response-to-fertilization-in-caenorhabditis-elegans
#16
Maryam Ataeian, Justus Tegha-Dunghu, Donna G Curtis, Ellen M E Sykes, Ashkan Nozohourmehrabad, Megha Bajaj, Karen Cheung, Martin Srayko
In most animals, female meiosis completes only after fertilization. Sperm entry has been implicated in providing a signal for the initiation of the final meiotic processes, however, a maternal component required for this process has not been previously identified. We report the characterization of a novel family of three highly similar paralogs (memi-1, memi-2, memi-3) that encode oocyte-specific proteins. A hypermorphic mutation memi-1(sb41) results in failure to exit female meiosis II properly, however, loss of all three paralogs results in a "skipped meiosis II" phenotype...
October 11, 2016: Genetics
https://www.readbyqxmd.com/read/27723199/synthesis-of-highly-selective-submicromolar-microcystin-based-inhibitors-of-protein-phosphatase-pp-2a-over-pp1
#17
Miriam Fontanillo, Ivan Zemskov, Maximilian Häfner, Ulrike Uhrig, Francesca Salvi, Bernd Simon, Valentin Wittmann, Maja Köhn
Research and therapeutic targeting of the phosphoserine/threonine phosphatases PP1 and PP2A is hindered by the lack of selective inhibitors. The microcystin (MC) natural toxins target both phosphatases with equal potency, and their complex synthesis has complicated structure-activity relationship studies in the past. We report herein the synthesis and biochemical evaluation of 11 MC analogues, which was accomplished through an efficient strategy combining solid- and solution-phase approaches. Our approach led to the first MC analogue with submicromolar inhibitory potency that is strongly selective for PP2A over PP1 and does not require the complex lipophilic Adda group...
November 2, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27716204/insulin-growth-factor-1-like-receptor-igf-1r
#18
Gopal Iyer, James Price, Shay Bourgeois, Eric Armstrong, Shyhmin Huang, Paul M Harari
BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and several other human cancers. Monoclonal antibodies, such as cetuximab that block EGFR signaling, have emerged as valuable molecular targeting agents in clinical cancer therapy. Prolonged exposure to cetuximab can result in cells acquiring resistance by a process that remains incompletely understood. METHODS: In this study, we analyzed the immediate early molecular response of cetuximab on physical interactions between EGFR and Insulin growth factor 1 like receptor (IGF-1R) in head and neck cancer cells that are resistant to cetuximab...
October 6, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27697110/oct4-resetting-by-aurkb-pp1-cell-cycle-axis-determines-the-identity-of-mouse-embryonic-stem-cells
#19
Jihoon Shin, Hong-Duk Youn
In embryonic stem cells (ESCs), cell cycle regulation is deeply connected to pluripotency. Especially, core transcription factors (CTFs) which are essential to maintain the pluripotency transcription programs should be reset during M/G1 transition. However, it remains unknown about how CTFs are governed during cell cycle progression. Here, we describe that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) axis during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle related target genes in determining the identity of ESCs...
September 29, 2016: BMB Reports
https://www.readbyqxmd.com/read/27681385/de-novo-missense-variants-in-ppp1cb-are-associated-with-intellectual-disability-and-congenital-heart-disease
#20
Lijiang Ma, Yavuz Bayram, Heather M McLaughlin, Megan T Cho, Alyson Krokosky, Clesson E Turner, Kristin Lindstrom, Caleb P Bupp, Katey Mayberry, Weiyi Mu, Joann Bodurtha, Veronique Weinstein, Neda Zadeh, Wendy Alcaraz, Zöe Powis, Yunru Shao, Daryl A Scott, Andrea M Lewis, Janson J White, Shalani N Jhangiani, Elif Yilmaz Gulec, Seema R Lalani, James R Lupski, Kyle Retterer, Rhonda E Schnur, Ingrid M Wentzensen, Sherri Bale, Wendy K Chung
Intellectual disabilities are genetically heterogeneous and can be associated with congenital anomalies. Using whole-exome sequencing (WES), we identified five different de novo missense variants in the protein phosphatase-1 catalytic subunit beta (PPP1CB) gene in eight unrelated individuals who share an overlapping phenotype of dysmorphic features, macrocephaly, developmental delay or intellectual disability (ID), congenital heart disease, short stature, and skeletal and connective tissue abnormalities. Protein phosphatase-1 (PP1) is a serine/threonine-specific protein phosphatase involved in the dephosphorylation of a variety of proteins...
December 2016: Human Genetics
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