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https://www.readbyqxmd.com/read/28319894/resolvin-d1-via-prevention-of-ros-mediated-shp2-inactivation-protects-endothelial-adherens-junction-integrity-and-barrier-function
#1
Rima Chattopadhyay, Somasundaram Raghavan, Gadiparthi N Rao
Resolvins are a novel class of lipid mediators that play an important role in the resolution of inflammation, although the underlying mechanisms are not very clear. To explore the anti-inflammatory mechanisms of resolvins, we have studied the effects of resolvin D1 (RvD1) on lipopolysaccharide (LPS)-induced endothelial barrier disruption as it is linked to propagation of inflammation. We found that LPS induces endothelial cell (EC) barrier disruption via xanthine oxidase (XO)-mediated reactive oxygen species (ROS) production, protein tyrosine phosphatase SHP2 inactivation and Fyn-related kinase (Frk) activation leading to tyrosine phosphorylation of α-catenin and VE-cadherin and their dissociation from each other affecting adherens junction (AJ) integrity and thereby increasing endothelial barrier permeability...
March 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/28286257/grouper-epinephelus-coioides-tcr-signaling-pathway-was-involved-in-response-against-cryptocaryon-irritans-infection
#2
Ze-Xiang Li, Yan-Wei Li, Shun Xu, Yang Xu, Ze-Quan Mo, Xue-Ming Dan, Xiao-Chun Luo
T cell activation is a complicated process accompanying with the activation of T cell receptor (TCR) signaling pathway, which is not well described in teleost fish. The initiation of this pathway depends on the interaction of membrane TCR co-receptors (e.g. CD4/8, CD3 and CD45) and a series of cytoplasmic protein tyrosine kinases (e.g. Lck, Fyn and ZAP70). Cyptocaryon irritans is a ciliate pathogen of marine fish white spot disease causing huge economic lost in marine aquaculture. This parasite can infect fish gill and skin and is considered to be a good pathogen model for fish gill and skin mucosal immunity...
March 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28275669/data-supporting-the-role-of-fyn-in-embryonic-sciatic-nerve-fasciculation
#3
Tomohiro Torii, Yuki Miyamoto, Kazuko Kawahara, Akito Tanoue, Yoichi Seki, Takako Morimoto, Masahiro Yamamoto, Junji Yamauchi
Fyn is the cytoplasmic tyrosine kinase that has critical roles in many aspects of biological functions. In the central [1] and peripheral nervous systems [2], [3], Fyn plays the key role in initiating myelination by myelin-forming glial cells (Schwann cells and oligodendrocytes). Herein we provide the data regarding the role of Fyn in fasciculation and branching of embryonic peripheral nerves.
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28266558/selective-induction-of-alternatively-spliced-fynt-isoform-by-tnf-facilitates-persistent-inflammatory-responses-in-astrocytes
#4
Chingli Lee, Clara Y B Low, Siew Ying Wong, Mitchell K P Lai, Michelle G K Tan
Fyn tyrosine kinase has been implicated in the pathogenesis of Alzheimer's disease (AD). We have previously reported that upregulation of the FynT isoform in AD brains was partly associated with astrocyte activation. In this study, we demonstrated selective FynT induction in murine cortex and primary astrocyte culture after prolonged exposure to inflammatory stimulants, suggesting that FynT may mediate persistent neuroinflammation. To delineate the functional role of astrocytic FynT in association with TNF-mediated inflammatory responses, immortalized normal human astrocytes (iNHA) stably expressing FynT kinase constitutively active (FynT-CA) or kinase dead (FynT-KD) mutants were treated with TNF and compared for inflammatory responses using high-throughput real-time RT-PCR and Luminex multi-analyte immunoassays...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28245069/synapsins-regulate-bdnf-mediated-synaptic-potentiation-and-axon-elongation-by-acting-on-membrane-rafts
#5
Hung-Teh Kao, Kanghyun Ryoo, Albert Lin, Stephen R Janoschka, George J Augustine, Barbara Porton
In neurons, intracellular membrane rafts are essential for specific actions of brain-derived neurotrophic factor (BDNF), which include the regulation of axon outgrowth, growth cone turning and synaptic transmission. Virtually all the actions of BDNF are mediated by binding to its receptor, TrkB. The association of TrkB with the tyrosine kinase, Fyn, is critical for its localization to intracellular membrane rafts. Here, we show that synapsins, a family of highly amphipathic neuronal phosphoproteins, regulate membrane raft lipid composition and consequently, the ability of BDNF to regulate axon/neurite development and potentiate synaptic transmission...
February 28, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28176147/antagonism-of-dopamine-d2-receptors-alters-phosphorylation-of-fyn-in-the-rat-medial-prefrontal-cortex
#6
Li-Min Mao, John Q Wang
Several Src family kinase (SFK) members are expressed in the mammalian brain and serve as key kinases in the regulation of a variety of cellular and synaptic events. These SFKs may be subject to the modulation by dopamine, although this topic has been investigated incompletely. In this study, we explored whether dopamine D2 receptors (D2Rs) regulate SFKs in adult rat brains in vivo. We investigated the role of D2Rs in two forebrain areas, the medial prefrontal cortex (mPFC) and hippocampus, since dopamine plays a pivotal role in regulating activity of mPFC and hippocampal neurons and D2Rs are expressed in these regions...
April 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28156097/confinement-and-stabilization-of-fyn-sh3-folding-intermediate-mimetics-within-the-cavity-of-the-chaperonin-groel-demonstrated-by-relaxation-based-nmr
#7
David S Libich, Vitali Tugarinov, Rodolfo Ghirlando, G Marius Clore
The interaction of two folding intermediate mimetics of the model protein substrate Fyn SH3 with the chaperonin GroEL, a supramolecular foldase/unfoldase machine, has been investigated by (15)N relaxation-based nuclear magnetic resonance spectroscopy (lifetime line broadening, dark state exchange saturation transfer, and relaxation dispersion). The two mimetics comprise C-terminal truncations of wild-type and triple-mutant (A39V/N53P/V55L) Fyn SH3 in which the C-terminal strand of the SH3 domain is unfolded, while preserving the remaining domain structure...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28137917/elevating-cxcr7-improves-angiogenic-function-of-epcs-via-akt-gsk-3%C3%AE-fyn-mediated-nrf2-activation-in-diabetic-limb-ischemia
#8
Xiaozhen Dai, Xiaoqing Yan, Jun Zeng, Jing Chen, Yuehui Wang, Jun Chen, Yan Li, Michelle T Barati, Kupper A Wintergerst, Kejian Pan, Matthew A Nystoriak, Daniel J Conklin, Gregg Rokosh, Paul N Epstein, Xiaokun Li, Yi Tan
RATIONALE: Endothelial progenitor cells (EPCs) respond to stromal cell-derived factor 1 (SDF-1) through chemokine receptors CXCR7 and CXCR4. Whether SDF-1 receptors involves in diabetes mellitus-induced EPCs dysfunction remains unknown. OBJECTIVE: To determine the role of SDF-1 receptors in diabetic EPCs dysfunction. METHODS AND RESULTS: CXCR7 expression, but not CXCR4 was reduced in EPCs from db/db mice, which coincided with impaired tube formation...
March 3, 2017: Circulation Research
https://www.readbyqxmd.com/read/28125091/microrna-466-inhibits-tumor-growth-and-bone-metastasis-in-prostate-cancer-by-direct-regulation-of-osteogenic-transcription-factor-runx2
#9
Melissa Colden, Altaf A Dar, Sharanjot Saini, Priya V Dahiya, Varahram Shahryari, Soichiro Yamamura, Yuichiro Tanaka, Gary Stein, Rajvir Dahiya, Shahana Majid
MicroRNAs (miRNAs) have emerged as key players in cancer progression and metastatic initiation yet their importance in regulating prostate cancer (PCa) metastasis to bone has begun to be appreciated. We employed multimodal strategy based on in-house PCa clinical samples, publicly available TCGA cohorts, a panel of cell lines, in silico analyses, and a series of in vitro and in vivo assays to investigate the role of miR-466 in PCa. Expression analyses revealed that miR-466 is under-expressed in PCa compared to normal tissues...
January 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28112226/click-chemistry-based-high-throughput-screening-platform-for-modulators-of-ras-palmitoylation
#10
Lakshmi Ganesan, Peyton Shieh, Carolyn R Bertozzi, Ilya Levental
Palmitoylation is a widespread, reversible lipid modification that has been implicated in regulating a variety of cellular processes. Approximately one thousand proteins are annotated as being palmitoylated, and for some of these, including several oncogenes of the Ras and Src families, palmitoylation is indispensable for protein function. Despite this wealth of disease-relevant targets, there are currently few effective pharmacological tools to interfere with protein palmitoylation. One reason for this lack of development is the dearth of assays to efficiently screen for small molecular inhibitors of palmitoylation...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#11
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28092037/structural-characterization-of-monomeric-dimeric-state-of-p59-fyn-sh2-domain
#12
Radu Huculeci, Fabien Kieken, Abel Garcia-Pino, Lieven Buts, Nico van Nuland, Tom Lenaerts
Src homology 2 (SH2) domains are key modulators in various signaling pathways allowing the recognition of phosphotyrosine sites of different proteins. Despite the fact that SH2 domains acquire their biological functions in a monomeric state, a multitude of reports have shown their tendency to dimerize. Here, we provide a technical description on how to isolate and characterize by gel filtration, circular dichroism (CD), and nuclear magnetic resonance (NMR) each conformational state of p59(fyn) SH2 domain.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28077797/repression-of-fyn-related-kinase-in-breast-cancer-cells-is-associated-with-promoter-site-specific-cpg-methylation
#13
Edward T Bagu, Sayem Miah, Chenlu Dai, Travis Spriggs, Yetunde Ogunbolude, Erika Beaton, Michelle Sanders, Raghuveera K Goel, Keith Bonham, Kiven E Lukong
The triple-negative breast cancer subtype is highly aggressive and has no defined therapeutic target. Fyn-related kinase (FRK) is a non-receptor tyrosine kinase, reported to be downregulated in breast cancer and gliomas, where it is suggested to have tumor suppressor activity. We examined the expression profile of FRK in a panel of 40 breast cancer cells representing all the major subtypes, as well as in 4 non-malignant mammary epithelial cell lines. We found that FRK expression was significantly repressed in a proportion of basal B breast cancer cell lines...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076826/identification-of-new-pyrrolo-2-3-d-pyrimidines-as-src-tyrosine-kinase-inhibitors-in%C3%A2-vitro-active-against-glioblastoma
#14
Francesca Musumeci, Anna Lucia Fallacara, Chiara Brullo, Giancarlo Grossi, Lorenzo Botta, Pierpaolo Calandro, Mario Chiariello, Miroslava Kissova, Emmanuele Crespan, Giovanni Maga, Silvia Schenone
In the last few years, several pyrrolo-pyrimidine derivatives have been either approved by the US FDA and in other countries for the treatment of different diseases or are currently in phase I/II clinical trials. Herein we present the synthesis and the characterization of a novel series of pyrrolo[2,3-d]pyrimidines, compounds 8a-j, and their activity against Glioblastoma multiforme (GBM). Docking studies and MM-GBSA analysis revealed the ability of such compounds to efficiently interact with the ATP binding site of Src...
February 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28033507/regulatory-region-genetic-variation-is-associated-with-fyn-expression-in-alzheimer-s-disease
#15
Jeffrey A Zahratka, Yvonne Shao, McKenzie Shaw, Kaitlin Todd, Shane V Formica, Maria Khrestian, Thomas Montine, James B Leverenz, Lynn M Bekris
Neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau, are a key pathologic feature of Alzheimer's disease (AD). Tau phosphorylation is under the control of multiple kinases and phosphatases, including Fyn. Previously, our group found an association between 2 regulatory single nucleotide polymorphisms in the FYN gene with increased tau levels in the cerebrospinal fluid. In this study, we hypothesized that Fyn expression in the brain is influenced by AD status and genetic content. We found that Fyn protein, but not messenger RNA, levels were increased in AD patients compared to cognitively normal controls and are associated with regulatory region single nucleotide polymorphisms...
March 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27993968/mechanisms-of-acquired-drug-resistance-to-the-hdac6-selective-inhibitor-ricolinostat-reveals-rational-drug-drug-combination-with-ibrutinib
#16
Jennifer E Amengual, Sathyen A Prabhu, Maximilian Lombardo, Kelly M Zullo, Paul M Johannet, Yulissa Gonzalez, Luigi Scotto, Xavier Jirau-Serrano, Ying Wei, Jimmy K Duong, Renu Nandakumar, Serge Cremers, Akanksha Verma, Olivier Elemento, Owen A O'Connor
PURPOSE: Pan-class I/II histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. ACY-1215 (ricolinostat) is a first in class selective HDAC6 inhibitor. To better understand the discrete function of HDAC6 and its role in lymphoma, we developed a lymphoma cell line resistant to ACY-1215. EXPERIMENTAL DESIGN: The diffuse large B-cell lymphoma cell line OCI-Ly10 was exposed to increasing concentrations of ACY-1215 over an extended period of time, leading to the development of a resistant cell line...
December 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27975258/proximity-ligation-assay-a-tool-to-study-endogenous-interactions-between-tau-and-its-neuronal-partners
#17
Alexis Bretteville, Florie Demiautte, Julien Chapuis
Tau is a microtubule associated protein (MAP) that is expressed in neurons of the central nervous system. Tau proteins are deregulated in a group of pathologies, including Alzheimer's disease, commonly called tauopathies. Therefore intensive research has been conducted to understand both the regulation of Tau and its involvement in neuronal cellular pathways. Since its originally described interactor tubulin, Tau has been described to interact with several other proteins, including tyrosine kinases (Src, Fyn, Lck) and Phospholipase C-γ...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27940916/hierarchical-crmp2-posttranslational-modifications-control-nav1-7-function
#18
Erik T Dustrude, Aubin Moutal, Xiaofang Yang, Yuying Wang, May Khanna, Rajesh Khanna
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27940153/fyn-kinase-regulates-translation-in-mammalian-mitochondria
#19
Emine C Koc, Jennifer L Miller-Lee, Hasan Koc
BACKGROUND: Mitochondrial translation machinery solely exists for the synthesis of 13 mitochondrially-encoded subunits of the oxidative phosphorylation (OXPHOS) complexes in mammals. Therefore, it plays a critical role in mitochondrial energy production. However, regulation of the mitochondrial translation machinery is still poorly understood. In comprehensive proteomics studies with normal and diseased tissues and cell lines, we and others have found the majority of mitochondrial ribosomal proteins (MRPs) to be phosphorylated...
March 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27926876/potentiation-of-synaptic-glun2b-nmdar-currents-by-fyn-kinase-is-gated-through-bdnf-mediated-disinhibition-in-spinal-pain-processing
#20
Michael E Hildebrand, Jian Xu, Annemarie Dedek, Yi Li, Ameet S Sengar, Simon Beggs, Paul J Lombroso, Michael W Salter
In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropathic pain. We find that BDNF mediates NMDAR potentiation through activation of TrkB and phosphorylation of the GluN2B subunit by the Src-family kinase Fyn...
December 6, 2016: Cell Reports
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