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https://www.readbyqxmd.com/read/28230313/crosstalk-between-smad2-3-and-specific-isoforms-of-erk-in-tgf-%C3%AE-1-induced-timp-3-expression-in-rat-chondrocytes
#1
Yanhui Zhu, Jianhua Gu, Tong Zhu, Chen Jin, Xiaopeng Hu, Xiang Wang
This study investigated the roles of ERK1 and ERK2 in transforming growth factor-β1 (TGF-β1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-β1...
February 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28228552/core-engagement-with-%C3%AE-arrestin-is-dispensable-for-agonist-induced-vasopressin-receptor-endocytosis-and-erk-activation
#2
Punita Kumari, Ashish Srivastava, Eshan Ghosh, Ravi Ranjan, Shalini Dogra, Prem N Yadav, Arun K Shukla
G Protein-Coupled Receptors (GPCRs) exhibit highly conserved activation and signaling mechanisms where agonist stimulation leads to coupling of heterotrimeric G proteins and generation of second messenger response. This is followed by receptor phosphorylation, primarily in the carboxyl-terminus but also in the cytoplasmic loops, and subsequent binding of arrestins. GPCRs typically recruit arrestins through two different set of interactions, one involving phosphorylated receptor tail and the other mediated by the receptor core...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28218497/chemotherapy-induces-tumor-immune-evasion-by-upregulation-of-programmed-cell-death-ligand%C3%A2-1-expression-in-bone-marrow-stromal-cells
#3
Mengqi Yang, Panpan Liu, Kefeng Wang, Christophe Glorieux, Yumin Hu, Shijun Wen, Wenqi Jiang, Peng Huang
Programmed cell death ligand 1 (PD-L1) is a negative regulator of the immune response that enables tumor cells to escape T-cell immunity. Although PD-L1 expression in cancer cells has been extensively studied, the expression of PD-L1 in stromal cells and its clinical significance remain largely unknown. Here, we show that bone marrow stromal cells express a low level of PD-L1 and that this molecule is significantly upregulated by key drugs used in the treatment of lymphoma at clinically relevant concentrations...
December 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28197631/repositioning-of-amprenavir-as-a-novel-extracellular-signal-regulated-kinase-2-inhibitor-and-apoptosis-inducer-in-mcf-7-human-breast-cancer
#4
Wenchun Jiang, Xin Li, Tongyu Li, Hailian Wang, Wei Shi, Ping Qi, Chunyang Li, Jie Chen, Jinku Bao, Guodong Huang, Yi Wang
Computational drug repositioning by virtually screening existing drugs for additional therapeutic usage could efficiently accelerate anticancer drug discovery. Herein, a library of 1447 Food and Drug Administration (FDA)-approved small molecule drugs was screened in silico for inhibitors of extracellular signal-regulated kinase 2 (ERK2). Then, in vitro kinase assay demonstrated amprenavir, a HIV-1 protease inhibitor, as a potential kinase inhibitor of ERK2. The in vivo kinase assay indicated that amprenavir could inhibit ERK2-mediated phosphorylation of BimEL at Ser69...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28193531/mutation-of-a-putative-map-kinase-consensus-site-regulates-ncam-endocytosis-and-ncam-dependent-neurite-outgrowth
#5
Tobias Goschzik, Harold Cremer, Vinayaga S Gnanapragassam, Rüdiger Horstkorte, Kaya Bork, Simone Diestel
The cytoplasmic domain of the neural cell adhesion molecule NCAM contains several putative serine/threonine phosphorylation sites whose functions are largely unknown. Human NCAM140 (NCAM140) possesses a potential MAP kinase phosphorylation site at threonine (T) 803. The aim of this study was to analyze a possible phosphorylation of NCAM140 by MAP kinases and to identify the functional role of T803. We found that NCAM140 is phosphorylated by the MAP kinase ERK2 in vitro. Exchange of T803 to aspartic acid (D) which mimics constitutive phosphorylation at the respective position resulted in increased endocytosis compared to NCAM140 in neuroblastoma cells and primary neurons...
February 10, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28192403/a-double-negative-feedback-loop-between-epcam-and-erk-contributes-to-the-regulation-of-epithelial-mesenchymal-transition-in-cancer
#6
N V Sankpal, T P Fleming, P K Sharma, H J Wiedner, W E Gillanders
Epithelial-mesenchymal transition (EMT) is an important biological process that has been implicated in cancer metastasis. Epithelial cell adhesion molecule (EpCAM) is expressed at the basolateral membrane of most normal epithelial cells but is overexpressed in many epithelial cancers. In our studies on the role of EpCAM in cancer biology, we observed that EpCAM expression is decreased in mesenchymal-like primary cancer specimens in vivo and following induction of EMT in cancer cell lines in vitro. Extracellular signal-related kinase (ERK) is a key regulator of EMT...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28183201/effect-of-titanium-dioxide-nanoparticles-tio2-nps-on-the-expression-of-mucin-genes-in-human-airway-epithelial-cells
#7
Gui Ok Kim, Yoon Seok Choi, Chang Hoon Bae, Si-Youn Song, Yong-Dae Kim
OBJECTIVE: Titanium dioxide nanoparticles (TiO2 NPs) are utilized with growing frequency for a wide variety of industrial applications. Recently, acute and chronic exposures to TiO2 NPs have been found to induce inflammatory response in the human respiratory tract. However, the effect and mechanism underlying the induction of major airway mucins by TiO2 NPs have not been elucidated. This study was conducted to characterize the effect of TiO2 NPs, and the mechanism involved, on the expressions of airway mucins in human airway epithelial cells...
January 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28174228/profiling-subcellular-protein-phosphatase-responses-to-coxsackievirus-b3-infection-of-cardiomyocytes
#8
Millie Shah, Christian M Smolko, Sarah Kinicki, Zachary D Chapman, David L Brautigan, Kevin A Janes
Cellular responses to stimuli involve dynamic and localized changes in protein kinases and phosphatases. Here, we report a generalized functional assay for high-throughput profiling of multiple protein phosphatases with subcellular resolution and apply it to analyze coxsackievirus B3 (CVB3) infection counteracted by interferon signaling. Using on-plate cell fractionation optimized for adherent cells, we isolate protein extracts containing active endogenous phosphatases from cell membranes, the cytoplasm, and the nucleus...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28168209/familial-amyloid-polyneuropathy-in-portugal-new-genes-modulating-age-at-onset
#9
Diana Santos, Teresa Coelho, Miguel Alves-Ferreira, Jorge Sequeiros, Denisa Mendonça, Isabel Alonso, Carolina Lemos, Alda Sousa
OBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HSP27, and YWHAZ - in a sample of 318 V30M Portuguese patients (106 families), currently under follow-up...
February 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28160492/a-prognostic-4-gene-expression-signature-for-squamous-cell-lung-carcinoma
#10
Jun Li, Jing Wang, Yanbin Chen, Lijie Yang, Sheng Chen
Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28145992/different-effects-of-prenatal-stress-on-erk2-creb-bcl-2-expression-in-the-hippocampus-and-the-prefrontal-cortex-of-adult-offspring-rats
#11
Zeen Zhu, Hongli Sun, Xiaojie Gong, Hui Li
It has become increasingly evident that prenatal stress and its psychological and physiological concomitants are associated with the pathophysiology of mood disorders. However, the mechanisms underlying the prenatal stress-induced offspring's anxiety disorders remain unknown. We recently reported that prenatal stress enhanced anxiety-like behavior in adult offspring rat, and involved N-methyl-D-aspartate receptor subunits, including NR1 and NR2A. In the present research, using the same prenatal stress model, we measured the ERK2/CREB/Bcl-2 mRNA levels by real-time PCR...
January 31, 2017: Neuroreport
https://www.readbyqxmd.com/read/28119463/erk-signaling-pathway-regulates-sleep-duration-through-activity-induced-gene-expression-during-wakefulness
#12
Cyril Mikhail, Angélique Vaucher, Sonia Jimenez, Mehdi Tafti
Wakefulness is accompanied by experience-dependent synaptic plasticity and an increase in activity-regulated gene transcription. Wake-induced genes are certainly markers of neuronal activity and may also directly regulate the duration of and need for sleep. We stimulated murine cortical cultures with the neuromodulatory signals that are known to control wakefulness in the brain and found that norepinephrine alone or a mixture of these neuromodulators induced activity-regulated gene transcription. Pharmacological inhibition of the various signaling pathways involved in the regulation of gene expression indicated that the extracellular signal-regulated kinase (ERK) pathway is the principal one mediating the effects of waking neuromodulators on gene expression...
January 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/28115189/rosmarinic-acid-counteracts-activation-of-hepatic-stellate-cells-via-inhibiting-the-ros-dependent-mmp-2-activity-involvement-of-nrf2-antioxidant-system
#13
Changfang Lu, Yu Zou, Yuzhang Liu, Yingcai Niu
Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28109909/erk2-zeb1-mir-101-1-axis-contributes-to-epithelial-mesenchymal-transition-and-cell-migration-in-cancer
#14
Kailash Chandra Mangalhara, Siddharth Manvati, Sunil Kumar Saini, Kalaiarasan Ponnusamy, Gaurav Agarwal, Suresh K Abraham, Rameshwar N K Bamezai
Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28107515/regulatory-mechanisms-underlying-the-expression-of-prolactin-receptor-in-chicken-granulosa-cells
#15
Shenqiang Hu, Raj Duggavathi, David Zadworny
Prolactin (PRL) has both pro- and anti-gonadal roles in the regulation of avian ovarian functions through its interaction with the receptor (PRLR). However, neither the pattern of expression of PRLR nor its regulatory mechanisms during follicle development have been clearly defined. The objective of the present study was to investigate mechanisms of PRLR expression in chicken granulosa cells. Levels of PRLR transcript were highest in the stroma and walls of follicles < 2 mm in diameter and progressively declined with the maturation of follicles...
2017: PloS One
https://www.readbyqxmd.com/read/28106280/erk1-directly-interacts-with-jnk1-leading-to-regulation-of-jnk1-c-jun-activity-and-cell-transformation
#16
Bong Seok Kang, Yoon Jin Hwang, Zigang Dong
ERK1 and ERK2 share a great deal of homology and have been presumed to have similar functions. Available antibodies recognize both isoforms making the elucidation of functional differences challenging. Mitogen-activated protein (MAP) kinase networks are commonly depicted in the literature as linear and sequential phosphorylation cascades; however, the activation of these pathways is not mutually exclusive. Little doubt exists that MAP kinases engage in crosstalk, but the extent or the direct effect of these "conversations" is unclear...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28100697/the-histone-demethylase-phf8-is-a-molecular-safeguard-of-the-ifn%C3%AE-response
#17
Elena Asensio-Juan, Raquel Fueyo, Stella Pappa, Simona Iacobucci, Carmen Badosa, Sergi Lois, Miriam Balada, Laia Bosch-Presegué, Alex Vaquero, Sara Gutiérrez, Carme Caelles, Carme Gallego, Xavier de la Cruz, Marian A Martínez-Balbás
A precise immune response is essential for cellular homeostasis and animal survival. The paramount importance of its control is reflected by the fact that its non-specific activation leads to inflammatory events that ultimately contribute to the appearance of many chronic diseases. However, the molecular mechanisms preventing non-specific activation and allowing a quick response upon signal activation are not yet fully understood. In this paper we uncover a new function of PHF8 blocking signal independent activation of immune gene promoters...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28098907/synergistic-combination-of-ys-1-and-adriamycin-inhibits-human-renal-cancer-through-erk1-2-signaling-pathway-in%C3%A2-vitro-and-in%C3%A2-vivo
#18
Xiaowen Yu, Qingqing Yang, Sensen Lin, Shengtao Yuan, Li Sun
Adriamycin (ADM) is a principal drug for the treatment of renal cell cancer (RCC). Due to its limited response and high renal and cardiac toxicity, synergistic effects of ADM in combination with other drugs have been widely researched. In this study, we found the combination between YS-1 and ADM, performed higher anticancer activity on 786-O human RCC cells in vitro and in vivo, than that reported on its anti-angiogenesis effect compared with monotherapy of ADM. Our data showed that when combined with ADM, YS-1 promoted the sensitivity of 786-O cells to ADM...
January 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098263/a-lab-on-a-chip-for-monolith-based-preconcentration-and-electrophoresis-separation-of-phosphopeptides
#19
Monica Araya-Farias, Szymon Dziomba, Benjamin Carbonnier, Mohamed Guerrouache, Ichraf Ayed, Nacera Aboud, Myriam Taverna, N Thuy Tran
A microdevice combining online preconcentration and separation of phosphopeptides was developed in a glass microchip. An ethylene glycol methacrylate phosphate (EGMP), acrylamide (AM) and bisacrylamide (BAA) based monolith was synthesized within microchannels through a photo-driven process. Morphological investigations revealed a homogeneous monolithic structure composed of uniform nodules (∼0.8 μm), with a large pore volume (0.62 cm(3) g(-1)) and sufficiently high specific surface area (34.1 m(2) g(-1))...
January 18, 2017: Analyst
https://www.readbyqxmd.com/read/28096188/erk1-2-phosphorylate-gab2-to-promote-a-negative-feedback-loop-that-attenuates-pi3k-akt-signaling
#20
Xiaocui Zhang, Geneviève Lavoie, Antoine Méant, Léo Aubert, Marie Cargnello, André Haman, Trang Hoang, Philippe P Roux
The scaffolding adapter protein Gab2 (Grb2-associated binder) promotes cell proliferation, survival and motility by engaging several signaling pathways downstream of growth factor and cytokine receptors. In particular, Gab2 plays essential roles in mast cells as it is required for PI3K (phosphoinositide 3-kinase) activation in response to Kit and the high-affinity IgE receptor. While the positive role of Gab2 in PI3K signaling is well documented, very little is known about the mechanisms that attenuate its function...
January 17, 2017: Molecular and Cellular Biology
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