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https://www.readbyqxmd.com/read/28921811/a-role-for-the-non-receptor-tyrosine-kinase-ack1-in-tnf-alpha-mediated-apoptosis-and-proliferation-in-human-intestinal-epithelial-caco-2-cells
#1
Xinmei Zhao, Chaolan Lv, Shenbo Chen, Fachao Zhi
The roles of tumor necrosis factor alpha (TNF-alpha) and its mediators in cellular processes related to intestinal diseases remain elusive. In this study, we aimed to determine the biological role of activated Cdc42-associated kinase 1 (ACK1) in TNF-alpha-mediated apoptosis and proliferation in Caco-2 cells. ACK1 expression was knocked down using ACK1-specific siRNAs, and ACK1 activity was disrupted using a small molecule ACK1 inhibitor. The Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) and the BrdU incorporation assays were used to measure apoptosis and cell proliferation, respectively...
September 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28919041/a-split-abl-kinase-for-direct-activation-in-cells
#2
Juan E Diaz, Charles W Morgan, Catherine E Minogue, Alexander S Hebert, Joshua J Coon, James A Wells
To dissect the cellular roles of individual kinases, it is useful to design tools for their selective activation. We describe the engineering of a split-cAbl kinase (sKin-Abl) that is rapidly activated in cells with rapamycin and allows temporal, dose, and compartmentalization control. Our design strategy involves an empirical screen in mammalian cells and identification of split site in the N lobe. This split site leads to complete loss of activity, which can be restored upon small-molecule-induced dimerization in cells...
August 24, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28916556/cell-scientist-to-watch-paul-timpson
#3
(no author information available yet)
Paul Timpson received his bachelor's degree from the University of Strathclyde, UK and completed his PhD under the supervision of Margaret Frame at the Beatson Institute for Cancer Research and the University of Glasgow in 2002, working on Src kinases and Rho family GTPases in cancer cell invasion. He then moved to the Garvan Institute of Medical Research in Sydney, Australia to work with Roger Daly on the actin-binding protein cortactin in several cancer models. Paul returned to the Beatson Institute in 2007 with the aid of an AstraZeneca postdoctoral research fellowship...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#4
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28915027/structure-and-dynamics-of-membrane-proteins-and-membrane-associated-proteins-with-native-bicelles-from-eukaryotic-tissues
#5
Sean T Smrt, Adrian W Draney, Indira Singaram, Justin L Lorieau
In vitro studies of protein structure, function and dynamics typically preclude the complex range of molecular interactions found in living tissues. In vivo studies elucidate these complex relationships, yet they are typically incompatible with the extensive and controlled biophysical experiments available in vitro. We present an alternative approach by extracting membranes from eukaryotic tissues to produce native bicelles to capture the rich and complex molecular environment of in vivo studies while retaining the advantages of in vitro experiments...
September 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28912461/vimentin-knockout-results-in-increased-expression-of-sub-endothelial-basement-membrane-components-and-carotid-stiffness-in-mice
#6
Benoit Langlois, Ekaterina Belozertseva, Ara Parlakian, Mustapha Bourhim, Jacqueline Gao-Li, Jocelyne Blanc, Lei Tian, Dario Coletti, Carlos Labat, Zhor Ramdame-Cherif, Pascal Challande, Véronique Regnault, Patrick Lacolley, Li Zhenlin
Intermediate filaments are involved in stress-related cell mechanical properties and in plasticity via the regulation of focal adhesions (FAs) and the actomyosin network. We investigated whether vimentin regulates endothelial cells (ECs) and vascular smooth muscle cells (SMCs) and thereby influences vasomotor tone and arterial stiffness. Vimentin knockout mice (Vim(-/-)) exhibited increased expression of laminin, fibronectin, perlecan, collagen IV and VE-cadherin as well as von Willebrand factor deposition in the subendothelial basement membrane...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911820/regulation-of-pannexin-channels-in-the-cns-by-src-family-kinases
#7
REVIEW
Alexander W Lohman, Nicholas L Weilinger, Silva Mf Santos, Jennifer Bialecki, Allison C Werner, Connor L Anderson, Roger J Thompson
Pannexins form single membrane channels that regulate the passage of ions, small molecules and metabolites between the intra- and extracellular compartments. In the central nervous system, these channels are integrated into numerous signaling cascades that shape brain physiology and pathology. Post-translational modification of pannexins is complex, with phosphorylation emerging as a prominent form of functional regulation. While much is still not known regarding the specific kinases and modified amino acids, recent reports support a role for Src family tyrosine kinases (SFK) in regulating pannexin channel activity...
September 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28910941/-effects-of-src-on-cervical-cancer-cells-proliferation-and-apoptosis-through-erk-signal-transduction-pathway
#8
Z C Song, L Ding, Z Y Ren, X S Sun, Q Yang, L Wang, M J Feng, C L Liu, J T Wang
Objective: To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway. Methods: Experimental study was carried out in vitro. Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2. Then, the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM). Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2, c-Fos and c-Jun mRNA and protein respectively...
September 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28910325/src-and-fyn-dependent-apical-membrane-trafficking-events-control-endothelial-lumen-formation-during-vascular-tube-morphogenesis
#9
Dae Joong Kim, Pieter R Norden, Jocelynda Salvador, David M Barry, Stephanie L K Bowers, Ondine Cleaver, George E Davis
Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked apical membrane targeting of activated Src kinases to this apical domain during early and late stages of this process. Immunostaining for phosphotyrosine or phospho-Src reveals apical membrane staining in intracellular vacuoles initially. This is then followed by vacuole to vacuole fusion events to generate an apical luminal membrane, which is similarly decorated with activated phospho-Src kinases...
2017: PloS One
https://www.readbyqxmd.com/read/28903400/hyperglycemia-and-advanced-glycation-end-products-ages-suppress-the-differentiation-of-3t3-l1-preadipocytes
#10
Chia-Chu Chang, Chen-Yu Chen, Geen-Dong Chang, Ting-Huan Chen, Woan-Ling Chen, Hui-Chin Wen, Chih-Yang Huang, Chung-Ho Chang
Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901387/triptolide-blocks-the-stat3-signaling-pathway-through-induction-of-protein-tyrosine-phosphatase-shp-1-in-multiple-myeloma-cells
#11
Ji-Hun Kim, Byoungduck Park
Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis...
September 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28899900/ret-receptor-tyrosine-kinase-sustains-proliferation-and-tissue-maturation-in-intestinal-epithelia
#12
Daniel Perea, Jordi Guiu, Bruno Hudry, Chrysoula Konstantinidou, Alexandra Milona, Dafni Hadjieconomou, Thomas Carroll, Nina Hoyer, Dipa Natarajan, Jukka Kallijärvi, James A Walker, Peter Soba, Nikhil Thapar, Alan J Burns, Kim B Jensen, Irene Miguel-Aliaga
Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation...
September 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28893976/teaching-an-old-drug-new-tricks-agonism-antagonism-and-biased-signaling-of-pilocarpine-through-m3-muscarinic-acetylcholine-receptor
#13
Alexey Pronin, Qiang Wang, Vladlen Z Slepak
Pilocarpine is a prototypical drug used to treat glaucoma and dry mouth and classified as either a full or partial muscarinic agonist. Here, we report several unexpected results pertaining to its interaction with muscarinic M3 receptor (M3R). We found that pilocarpine was 1,000 times less potent in stimulating mouse eye pupil constriction than muscarinic agonists oxotremorin-M (Oxo-M) or carbachol (CCh), even though all three ligands have similar Kd values for M3R. In contrast to CCh or Oxo-M, pilocarpine does not induce Ca2+ mobilization via endogenous M3R in HEK293T or mouse insulinoma MIN6 cells...
September 11, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28892098/correlation-between-e-cadherin-interactions-survivin-expression-and-apoptosis-in-mdck-and-ts-src-mdck-cell-culture-models
#14
Janne Capra, Sinikka Eskelinen
Survivin, a member of inhibitor of apoptosis (IAP) protein family, is a multifunctional protein expressed in most cancers. In addition to inhibition of apoptosis, it regulates proliferation and promotes migration. Its presence and function in cells is strongly regulated via transcription factors, intracellular localization, and degradation. We analyzed the presence of survivin at protein level in various culture environments and under activation of Src tyrosine kinase in epithelial canine kidney MDCK cells in order to elucidate factors controlling survivin 'lifespan'...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28891817/neutrophil-fc%C3%AE-riia-promotes-igg-mediated-glomerular-neutrophil-capture-via-abl-src-kinases
#15
Hiroshi Nishi, Kazuhiro Furuhashi, Xavier Cullere, Gurpanna Saggu, Mark J Miller, Yunfeng Chen, Florencia Rosetti, Samantha L Hamilton, Lihua Yang, Spencer P Pittman, Jiexi Liao, Jan M Herter, Jeffrey C Berry, Daniel J DeAngelo, Cheng Zhu, George C Tsokos, Tanya N Mayadas
The kidney glomerular capillaries are frequent sites of immune complex deposition and subsequent neutrophil accumulation in post-infectious and rapidly progressive glomerulonephritis. However, the mechanisms of neutrophil recruitment remain enigmatic, and there is no targeted therapeutic to avert this proximal event in glomerular inflammation. The uniquely human activating Fc receptor FcγRIIA promotes glomerular neutrophil accumulation and damage in anti-glomerular basement membrane-induced (anti-GBM-induced) glomerulonephritis when expressed on murine neutrophils...
September 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28888895/regulation-of-platelet-activation-and-thrombus-formation-by-reactive-oxygen-species
#16
Jianlin Qiao, Jane F Arthur, Elizabeth E Gardiner, Robert K Andrews, Lingyu Zeng, Kailin Xu
Reactive oxygen species (ROS) are generated within activated platelets and play an important role in regulating platelet responses to collagen and collagen-mediated thrombus formation. As a major collagen receptor, platelet-specific glycoprotein (GP)VI is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin domain, a transmembrane domain and a cytoplasmic tail. GPVI forms a functional complex with the Fc receptor γ-chain (FcRγ) that, following receptor dimerization, signals via an intracellular immunoreceptor tyrosine-based activation motif (ITAM), leading to rapid activation of Src family kinase signaling pathways...
September 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28882999/mir-193b-regulated-signaling-networks-serve-as-tumor-suppressors-in-liposarcoma-and-promote-adipogenesis-in-adipose-derived-stem-cells
#17
Ying Z Mazzu, Yulan Hu, Rajesh K Soni, Kelly M Mojica, Li-Xuan Qin, Phaedra Agius, Zachary M Waxman, Aleksandra Mihailovic, Nicholas D Socci, Ronald C Hendrickson, Thomas Tuschl, Samuel Singer
Well-differentiated and dedifferentiated liposarcomas (WDLS/DDLS) account for approximately 13% of all soft tissue sarcoma in adults and cause substantial morbidity or mortality in the majority of patients. In this study, we evaluated the functions of miRNA (miR-193b) in liposarcoma in vitro and in vivo. Deep RNA sequencing on 93 WDLS, 145 DDLS and 12 normal fat samples demonstrated that miR-193b was significantly underexpressed in DDLS compared to normal fat. Re-introduction of miR-193b induced apoptosis in liposarcoma cells and promoted adipogenesis in human adipose-derived stem cells (ASC)...
September 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28881828/shp2-negatively-regulates-hla-abc-and-pd-l1-expression-via-stat1-phosphorylation-in-prostate-cancer-cells
#18
Zhuqing Liu, Yu Zhao, Juemin Fang, Ran Cui, Yuanyuan Xiao, Qing Xu
Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) is a ubiquitous protein tyrosine phosphatase that activates the signal transduction pathways of several growth factors and cytokines. In our study, SHP2 expression was very high in prostate cancer (PCa) cell lines, and the expression of phospho-signal transducer and activator of transcription 1 (p-STAT1) and STAT1 was very low. SHP2 knockdown upregulated the expression of p-STAT1 and downregulated phospho-extracellular signal regulated kinase (p-ERK)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879797/amorfrutin-a-inhibits-tnf-%C3%AE-induced-jak-stat-signaling-cell-survival-and-proliferation-of-human-cancer-cells
#19
Chunliu Mi, Juan Ma, Ke Si Wang, Zhe Wang, Ming Yue Li, Jun Bo Li, Xuezheng Li, Lian Xun Piao, Guang Hua Xu, Xuejun Jin
CONTEXT: Amorfrutin A is a natural product isolated from the fruits of Amorpha fruticosa L. and has been shown to exhibit multiple bioeffector functions. In the present study, we investigated whether amorfrutin A exerts anticancer effects by inhibiting STAT3 activation in cervical cancer cells. OBJECTIVE: To investigate the effectiveness of amorfrutin A as a treatment of cancer, and determine the underlying pharmacological mechanism of action. MATERIALS AND METHODS: HeLa, SK-Hep1, MDA-MB-231 and HCT116 cells were used in this study...
September 7, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28879169/herpes-simplex-virus-type-1-neuronal-infection-perturbs-golgi-apparatus-integrity-through-activation-of-src-tyrosine-kinase-and-dyn-2-gtpase
#20
Carolina Martin, Luis Leyton, Melissa Hott, Yennyfer Arancibia, Carlos Spichiger, Mark A McNiven, Felipe A Court, Margarita I Concha, Patricia V Burgos, Carola Otth
Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance...
2017: Frontiers in Cellular and Infection Microbiology
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