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https://www.readbyqxmd.com/read/29141582/a-novel-interaction-between-kinase-activities-in-regulation-of-cilia-formation
#1
Nicole DeVaul, Katerina Koloustroubis, Rong Wang, Ann O Sperry
BACKGROUND: The primary cilium is an extension of the cell membrane that encloses a microtubule-based axoneme. Primary cilia are essential for transmission of environmental cues that determine cell fate. Disruption of primary cilia function is the molecular basis of numerous developmental disorders. Despite their biological importance, the mechanisms governing their assembly and disassembly are just beginning to be understood. Cilia growth and disassembly are essential events when cells exit and reenter into the cell cycle...
November 15, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#2
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29126937/coccinia-indica-agglutinin-a-17kda-pp2-like-phloem-lectin-affinity-purification-primary-structure-and-formation-of-self-assembled-filaments
#3
Kishore Babu Bobbili, Gottfried Pohlentz, Akkaladevi Narahari, Kaushal Sharma, A Surolia, Michael Mormann, Musti J Swamy
Phloem protein-2 (PP2) is an abundant soluble protein in the sieve elements in plants. Its lectin property was reported in various species. The primary structure of PP2 from Coccinia indica (Coccinia indica agglutinin, CIA17), determined by mass spectrometry, shows extensive homology with PP2 super family phloem lectins. Analysis of mass spectrometric data indicated the presence of 16 potential allelic variants of CIA17 with insignificant divergence in the primary structure. The primary structure contains an intramolecular disulfide bridge between Cys-34 and Cys-51, which is conserved across various cucurbit species and hence likely to be important for carbohydrate binding...
November 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29124352/brain-waves-from-an-isolated-cortex-contribution-of-the-anterior-insula-to-cognitive-functions
#4
Rinaldo Livio Perri, Marika Berchicci, Valentina Bianco, Donatella Spinelli, Francesco Di Russo
Using two independent electrical neuroimaging techniques (BESA and sLORETA), we tested a fMRI-seeded source modeling indicating that in visual discriminative tasks the anterior insula (aIns) participates in the generation of three prefrontal ERP components: the pN1 (at 115 ms), the pP1 (at 170 ms), and the pP2 (at 300 ms). This latter component represented the focus of the present study. Results showed that the pP2 had different activation profiles across hemispheres. The left aIns activity peaked at 420 ms (30 ms before the response) for both Go and No-go trials, that is independently from the ultimate choice (response or inhibition)...
November 9, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29097424/the-free-fatty-acid-receptor-1-promotes-airway-smooth-muscle-cell-proliferation-through-mek-erk-and-pi3k-akt-signaling-pathways
#5
Atsuko Matoba, Nao Matsuyama, Sumire Shibata, Eiji Masaki, Charles W Emala, Kentaro Mizuta
Obesity is a risk factor for asthma and influences airway hyperresponsiveness, which is in part modulated by airway smooth muscle proliferative remodeling. Plasma free fatty acids (FFAs) levels are elevated in obese individuals, and long-chain FFAs act as endogenous ligands for the free fatty acid receptor 1 (FFAR1), which couples to both Gq and Gi proteins. We examined whether stimulation of FFAR1 induces airway smooth muscle cell proliferation through classical MEK/ERK and/or PI3K/Akt signaling pathways. The long-chain FFAs (oleic acid and linoleic acid) and a FFAR1 agonist (GW9508) induced human airway smooth muscle (HASM) cell proliferation, which was inhibited by the MEK inhibitor U0126 and the PI3K inhibitor LY294002...
November 2, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29079540/il-18-contributes-to-bone-cancer-pain-by-regulating-glia-cells-and-neuron-interaction
#6
Su Liu, Yue-Peng Liu, You Lv, Jun-Li Yao, Dong-Mei Yue, Mao-Yin Zhang, Dun-Yi Qi, Gong-Jian Liu
BACKGROUND: Glia cells hyperactivity has been proposed to be responsible for chronic pain, however, the mechanisms remain unclear. IL-18, released from glial cells, has been reported to be involved in neuropathic pain. Here, we investigated the role of IL-18 in bone cancer pain. METHODS: Bone cancer pain was mimicked by injecting Walker-256 mammary gland carcinoma cells into the intramedullary space of the tibia in rats. Expression and location of IL-18 and IL-18 receptor were tested...
October 24, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29071723/immediate-cortical-adaptation-in-visual-and-non-visual-areas-functions-induced-by-monovision
#7
Fabrizio Zeri, Marika Berchicci, Shehzad A Naroo, Sabrina Pitzalis, Francesco Di Russo
KEY POINTS: Monovision is an optical correction for presbyopes that consists of correcting one eye for far distance and the other for near distance, creating a superimposition of an in-focus with a blurred image. Brain adaptation to monovision was studied in unexperienced observers by measuring visual evoked potentials from 64-channels. The first clear effect of monovision on visual evoked potentials was the C1 amplitude reduction, indicating that the unilateral blurring induced by monovision reduces feed-forward activity in primary visual area...
October 25, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29059150/protein-phosphatase-1-regulatory-subunit-1a-in-ewing-sarcoma-tumorigenesis-and-metastasis
#8
W Luo, C Xu, J Ayello, F Dela Cruz, J M Rosenblum, S L Lessnick, M S Cairo
Protein phosphatase inhibitors are often considered as tumor promoters. Protein phosphatase 1 regulatory subunit 1A (PPP1R1A) is a potent protein phosphatase 1 (PP1) inhibitor; however, its role in tumor development is largely undefined. Here we characterize, for the first time, the functions of PPP1R1A in Ewing sarcoma (ES) pathogenesis. We found that PPP1R1A is one of the top ranked target genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a GGAA microsatellite enhancer element...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29046399/dynamic-localization-of-a-yeast-development-specific-pp1-complex-during-prospore-membrane-formation-is-dependent-on-multiple-localization-signals-and-complex-formation
#9
Tsuyoshi S Nakamura, Yumi Numajiri, Yuuya Okumura, Junji Hidaka, Takayuki Tanaka, Ichiro Inoue, Yasuyuki Suda, Tetsuo Takahashi, Hideki Nakanishi, Xiao-Dong Gao, Aaron M Neiman, Hiroyuki Tachikawa
During the developmental process of sporulation in Saccharomyces cerevisiae, membrane structures called prospore membranes are formed de novo, expand, extend, round up, and finally become plasma membranes of the spores. GIP1 encodes a regulatory/targeting subunit of protein phosphatase type 1 that is required for sporulation. Gip1 recruits the catalytic subunit Glc7 to septin structures that form along the prospore membrane; however, the molecular basis of its localization and function is not fully understood...
October 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29042623/the-protein-phosphatase-1-regulator-nipp1-is-essential-for-mammalian-spermatogenesis
#10
Mónica Ferreira, Shannah Boens, Claudia Winkler, Kathelijne Szekér, Iris Verbinnen, Aleyde Van Eynde, Margarida Fardilha, Mathieu Bollen
NIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The deletion of NIPP1 in mice is early embryonic lethal, which has precluded functional studies in adult tissues. Hence, we have generated an inducible NIPP1 knockout model using a tamoxifen-inducible Cre recombinase transgene. The inactivation of the NIPP1 encoding alleles (Ppp1r8) in adult mice occurred very efficiently in testis and resulted in a gradual loss of germ cells, culminating in a Sertoli-cell only phenotype. Before the overt development of this phenotype Ppp1r8 (-/-) testis showed a decreased proliferation and survival capacity of cells of the spermatogenic lineage...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038521/pkc%C3%AE%C2%B5-phosphorylates-miip-and-promotes-colorectal-cancer-metastasis-through-inhibition-of-rela-deacetylation
#11
Tao Chen, Jingjie Li, Meidong Xu, Qin Zhao, Yingyong Hou, Liqing Yao, Yunshi Zhong, Ping-Chieh Chou, Wei Zhang, Pinghong Zhou, Yuhui Jiang
EGFR signaling is implicated in NF-κB activation. However, the concrete mechanisms by which the core transducer of NF-κB signaling pathway, RelA/p65 is regulated under EGFR activation remains to be further clarified. Here, we show that EGF stimulation induces PKCε-dependent phosphorylation of migration and invasion inhibitory protein (MIIP) at Ser303; this phosphorylation promotes the interaction between MIIP and RelA in the nucleus, by which MIIP prevents histone deacetylase 6 (HDAC6)-mediated RelA deacetylation, and thus enhances transcriptional activity of RelA and facilitates tumor metastasis...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28985363/protein-phosphatase-1-and-phosphatase-1-nuclear-targeting-subunit-dependent-regulation-of-dna-dependent-protein-kinase-and-non-homologous-end-joining
#12
Songli Zhu, Laura A Fisher, Tadayoshi Bessho, Aimin Peng
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a key role in mediating non-homologous end joining (NHEJ), a major repair pathway for DNA double-strand breaks (DSBs). The activation, function and dynamics of DNA-PKcs is regulated largely by its reversible phosphorylation at numerous residues, many of which are targeted by DNA-PKcs itself. Interestingly, these DNA-PKcs phosphorylation sites function in a distinct, and sometimes opposing manner, suggesting that they are differentially regulated via complex actions of both kinases and phosphatases...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28982702/phosphatase-regulated-recruitment-of-the-spindle-and-kinetochore-associated-ska-complex-to-kinetochores
#13
Sushama Sivakumar, Gary J Gorbsky
Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The spindle- and kinetochore-associated (Ska) complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1) to kinetochores...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28968740/activity-dependent-neuroplasticity-induced-by-an-enriched-environment-reverses-cognitive-deficits-in-scribble-deficient-mouse
#14
Muna L Hilal, Maité M Moreau, Claudia Racca, Vera L Pinheiro, Nicolas H Piguel, Marie-Josée Santoni, Steve Dos Santos Carvalho, Jean-Michel Blanc, Yah-Se K Abada, Ronan Peyroutou, Chantal Medina, Hélène Doat, Thomas Papouin, Laurent Vuillard, Jean-Paul Borg, Rivka Rachel, Aude Panatier, Mireille Montcouquiol, Stéphane H R Oliet, Nathalie Sans
Planar cell polarity (PCP) signaling is well known to play a critical role during prenatal brain development; whether it plays specific roles at postnatal stages remains rather unknown. Here, we investigated the role of a key PCP-associated gene scrib in CA1 hippocampal structure and function at postnatal stages. We found that Scrib is required for learning and memory consolidation in the Morris water maze as well as synaptic maturation and NMDAR-dependent bidirectional plasticity. Furthermore, we unveiled a direct molecular interaction between Scrib and PP1/PP2A phosphatases whose levels were decreased in postsynaptic density of conditional knock-out mice...
December 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28934390/protein-phosphatase-1-regulates-huntingtin-exon-1-aggregation-and-toxicity
#15
Joana Branco-Santos, Federico Herrera, Gonçalo M Poças, Yolanda Pires-Afonso, Flaviano Giorgini, Pedro M Domingos, Tiago F Outeiro
Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregation and toxicity in human cells and Drosophila neurons. We used bimolecular fluorescence complementation to show that expression of single phosphomimic mutations completely abolished HTTex1 aggregation in human cells...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934028/toward-neuroproteomics-in-biological-psychiatry-a-systems-approach-unravels-okadaic-acid-induced-alterations-in-the-neuronal-phosphoproteome
#16
Joana Machado Oliveira, Cristóvão B da Cruz E Silva, Thorsten Müller, Tânia Soares Martins, Marta Cova, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Neuroproteomics is an evolving field of postgenomic medicine, highlighting the convergence of psychiatry/neurology and proteomics, yet compared with neurogenetics, it has received little attention. This study in rat primary neuronal cultures provides an example of a neuroproteomic approach relevant to the study of psychiatric disease pathophysiology, focusing on Alzheimer's disease. In this context, okadaic acid (OA) is routinely used in experimental designs to investigate phosphorylation-mediated events. It is a potent protein phosphatase (PP) inhibitor, particularly of PP1 and PP2A...
September 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28931335/activation-of-erk-signalling-by-src-family-kinases-sfks-in-drg-neurons-contributes-to-hydrogen-peroxide-h2o2-induced-thermal-hyperalgesia
#17
Ajeet Kumar Singh, Manjula Vinayak
Concomitant generation of reactive oxygen species during tissue inflammation has been recognised as a major factor for the development and the maintenance of hyperalgesia, out of which H2O2 is the major player. However, molecular mechanism of H2O2 induced hyperalgesia is still obscure. The aim of present study is to analyse the mechanism of H2O2-induced hyperalgesia in rats. Intraplantar injection of H2O2 (5, 10 and 20 µmoles/paw) induced a significant thermal hyperalgesia in the hind paw, confirmed by increased c-Fos activity in dorsal horn of spinal cord...
October 2017: Free Radical Research
https://www.readbyqxmd.com/read/28910568/network-of-phosphatases-and-hdac-complexes-at-repressed-chromatin
#18
I J de Castro, H A Amin, V Vinciotti, P Vagnarelli
Tight regulation of gene expression is achieved by a variety of protein complexes that selectively bind chromatin, modify it and change its transcription competency. Histone acetylases (HATs) and deacetylases (HDACs) play an important role in this process. They can generate transcriptionally active or inactive chromatin through the addition (HATs) or removal (HDACs) of acetyl groups on histones, respectively. Repo-Man is a Protein Phosphatase 1 targeting subunit that accumulates on chromosomes during mitotic exit and mediates the removal of mitotic histone H3 phosphorylations...
September 14, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28893598/microcystins-synthesis-and-structure-activity-relationship-studies-toward-pp1-and-pp2a
#19
REVIEW
Miriam Fontanillo, Maja Köhn
Microcystins are highly toxic cyanotoxins responsible for plant, animal and human poisoning. Exposure to microcystins, mainly through drinkable water and contaminated food, is a current world health concern. Although it is quite challenging, the synthesis of these potent cyanotoxins, analogs and derivatives helps to evaluate their toxicological properties and to elucidate their binding mechanisms to their main targets Protein Phosphatase-1 (PP1) and -2A (PP2A). This review focuses on synthetic approaches to prepare microcystins and analogs and compiles structure-activity relationship (SAR) studies that describe the unique features of microcystins that make them so potent...
August 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28890776/discovery-of-a-potent-protein-kinase-d-inhibitor-insights-in-the-binding-mode-of-pyrazolo-3-4-d-pyrimidine-analogues
#20
Klaas Verschueren, Mathias Cobbaut, Joachim Demaerel, Lina Saadah, Arnout R D Voet, Johan Van Lint, Wim M De Borggraeve
In this study, we set out to rationally optimize PKD inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold. The lead compound for this study was 1-NM-PP1, which was previously found by us and others to inhibit PKD. In our screening we identified one compound (3-IN-PP1) displaying a 10-fold increase in potency over 1-NM-PP1, opening new possibilities for specific protein kinase inhibitors for kinases that show sensitivity towards pyrazolo[3,4-d]pyrimidine derived compounds. Interestingly the observed SAR was not in complete agreement with the commonly observed binding mode where the pyrazolo[3,4-d]pyrimidine compounds are bound in a similar fashion as PKD's natural ligand ATP...
March 1, 2017: MedChemComm
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