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https://www.readbyqxmd.com/read/28522860/involvement-of-fak-erk2-signaling-pathway-in-ckap2-induced-proliferation-and-motility-in-cervical-carcinoma-cell-lines
#1
Qi-Sang Guo, Yu Song, Ke-Qin Hua, Shu-Jun Gao
Cervical carcinoma is the fourth most common cause of death in woman, caused by human papillomavirus (HPV) infections and arising from the cervix. Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein, has been linked to tumorigenic effects. In the present study, we screened CKAP2 as a new candidate gene which promotes development of cervical carcinoma, in two independent datasets (TCGA and GSE27678). Results showed that CKAP2 expression was significantly up-regulated in cervical cancerous tissues compared with normal counterparts...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522560/the-effect-of-long-term-maternal-smoking-on-the-offspring-s-lung-health
#2
Suporn Sukjamnong, Yik Lung Chan, Razia Zakarya, Sonia Saad, Pawan Sharma, Rachana Santiyanont, Hui Chen, Brian G G Oliver
Maternal smoking during pregnancy contributes to long-term health problems in offspring, especially respiratory disorders which can manifest in either childhood or adulthood. Receptors for advanced glycation end-products (RAGE) are multi-ligand receptors abundantly localized in the lung, capable of responding to by-products of reactive oxygen species and pro-inflammatory responses. RAGE signalling is a key regulator of inflammation in cigarette smoking-related pulmonary diseases. However, the impact of maternal cigarette smoke exposure on lung RAGE signalling in the offspring is unclear...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28512266/activating-mapk1-erk2-mutation-in-an-aggressive-case-of-disseminated-juvenile-xanthogranuloma
#3
Rikhia Chakraborty, Oliver A Hampton, Harshal Abhyankar, Daniel J Zinn, Amanda Grimes, Brooks Skull, Olive Eckstein, Nadia Mahmood, David A Wheeler, Dolores Lopez-Terrada, Tricia L Peters, John M. Hicks, Tarek Elghetany, Robert Krance, Poulikos I Poulikakos, Miriam Merad, Kenneth L McClain, Carl E Allen, Donald W. Parsons
Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually benign and self-limiting. We present a case of atypical, aggressive JXG harboring a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1 gene, which encodes mitogen-activated protein kinase 1 or extracellular signal-regulated 2 (ERK2). Our analysis revealed that the mutation results in constitutive ERK activation that is resistant to BRAF or MEK inhibitors but susceptible to an ERK inhibitor. These data highlight the importance of identifying specific MAPK pathway alterations as part of the diagnostic workup for patients with histiocytic disorders rather than initiating empiric treatment with MEK inhibitors...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507546/extracellular-signal-regulated-kinase-signaling-in-cd4-expressing-cells-inhibits-osteochondromas
#4
Marie Wehenkel, Maripat Corr, Clifford S Guy, Benjamin A Edwards, Ashley H Castellaw, Christopher Calabrese, Gilles Pagès, Jacques Pouysségur, Peter Vogel, Maureen A McGargill
Defects in cartilage homeostasis can give rise to various skeletal disorders including osteochondromas. Osteochondromas are benign bone tumors caused by excess accumulation of chondrocytes, the main cell type of cartilage. The extracellular signal-regulated kinase (ERK) pathway is a major signaling node that functions within chondrocytes to regulate their growth and differentiation. However, it is not known whether the ERK pathway in other cell types regulates cartilage homeostasis. We show here that mice with a germline deficiency of Erk1 and a conditional deletion of Erk2 in cells that express CD4, or expressed CD4 at one point in development, unexpectedly developed bone deformities...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28474232/ets-targeted-therapy-can-it-substitute-for-mek-inhibitors
#5
REVIEW
Osamu Tetsu, Frank McCormick
BACKGROUND: The RAS/MAPK pathway has been intensively studied in cancer. Constitutive activation of ERK1 and ERK2 is frequently found in cancer cells from a variety of tissues. In clinical practice and clinical trials, small molecules targeting receptor tyrosine kinases or components in the MAPK cascade are used for treatment. MEK1 and MEK2 are ideal targets because these enzymes are physiologically important and have narrow substrate specificities and distinctive structural characteristics...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28471171/characterizing-the-chemical-space-of-erk2-kinase-inhibitors-using-descriptors-computed-from-molecular-dynamics-trajectories
#6
Jeremy Ash, Denis Fourches
Quantitative Structure-Activity Relationship (QSAR) models typically rely on 2D and 3D molecular descriptors to characterize chemicals and forecast their experimental activities. Previously, we showed that even the most reliable 2D QSAR models and structure-based 3D molecular docking techniques were not capable of accurately ranking a set of known inhibitors for the ERK2 kinase, a key player in various types of cancer. Herein, we calculated and analyzed a series of chemical descriptors computed from the molecular dynamics (MD) trajectories of ERK2-ligand complexes...
May 4, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28460635/transcriptomic-profiling-and-quantitative-high-throughput-qhts-drug-screening-of-cdh1-deficient-hereditary-diffuse-gastric-cancer-hdgc-cells-identify-treatment-leads-for-familial-gastric-cancer
#7
Ina Chen, Lesley Mathews-Greiner, Dandan Li, Abisola Abisoye-Ogunniyan, Satyajit Ray, Yansong Bian, Vivek Shukla, Xiaohu Zhang, Raj Guha, Craig Thomas, Berkley Gryder, Athina Zacharia, Joal D Beane, Sarangan Ravichandran, Marc Ferrer, Udo Rudloff
BACKGROUND: Patients with hereditary diffuse gastric cancer (HDGC), a cancer predisposition syndrome associated with germline mutations of the CDH1 (E-cadherin) gene, have few effective treatment options. Despite marked differences in natural history, histopathology, and genetic profile to patients afflicted by sporadic gastric cancer, patients with HDGC receive, in large, identical systemic regimens. The lack of a robust preclinical in vitro system suitable for effective drug screening has been one of the obstacles to date which has hampered therapeutic advances in this rare disease...
May 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28453902/lighting-up-kinase-action-in-platelets
#8
Albert Smolenski
Platelet functions are highly regulated by signaling networks involving at least 300 protein kinases [2]. Platelets express members of the mitogen-activated protein kinase (MAPK) family including p42 ERK2 and, at lower concentrations, p44 ERK1. Both ERK isoforms are activated by agonists like von Willebrand factor, collagen, thrombin, ADP and thromboxane A2 [3-7]. ERK activation depends on MAPK kinase (MKK-1 or MEK) and involves Gq, Gi, phospholipase C and Src family kinase signaling [5, 8]. Active ERK has been shown to stimulate thromboxane A2 production [5] and to contribute to platelet aggregation [4, 9]...
April 28, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28436422/rational-design-of-non-resistant-targeted-cancer-therapies
#9
Francisco Martínez-Jiménez, John P Overington, Bissan Al-Lazikani, Marc A Marti-Renom
Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420753/the-kinase-tpl2-activates-erk-and-p38-signaling-to-promote-neutrophilic-inflammation
#10
Kate Senger, Victoria C Pham, Eugene Varfolomeev, Jason A Hackney, Cesar A Corzo, Jenna Collier, Vivian W C Lau, Zhiyu Huang, Kajal Hamidzhadeh, Patrick Caplazi, Ivan Peng, A Francesca Setiadi, Ross Francis, Andres Paler-Martinez, Youngsu C Kwon, Vladimir Ramirez-Carrozzi, Yonglian Sun, Patricia W Grigg, Merone Roose-Girma, Surinder Jeet, Kai H Barck, Anna Pham, Naruhisa Ota, Connie Ha, Jeremy Stinson, Joseph Guillory, Lucinda Tam, Zora Modrusan, Claire Emson, Brent S McKenzie, Michael J Townsend, Richard A D Carano, Søren Warming, Domagoj Vucic, Jason DeVoss, Wyne P Lee, Jennie R Lill, Ali A Zarrin
Tumor progression locus 2 (TPL2; also known as MAP3K8) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that phosphorylates the MAPK kinases MEK1 and MEK2 (MEK1/2), which, in turn, activate the MAPKs extracellular signal-regulated kinase 1 (ERK1) and ERK2 (ERK1/2) in macrophages stimulated through the interleukin-1 receptor (IL-1R), Toll-like receptors (TLRs), or the tumor necrosis factor receptor (TNFR). We describe a conserved and critical role for TPL2 in mediating the effector functions of neutrophils through the activation of the p38 MAPK signaling pathway...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28418405/adenosine-a2a-receptor-and-erk-driven-impulsivity-potentiates-hippocampal-neuroblast-proliferation
#11
A Oliveros, C H Cho, A Cui, S Choi, D Lindberg, D Hinton, M-H Jang, D-S Choi
Dampened adenosine A2A receptor (A2AR) function has been implicated in addiction through enhancement of goal-directed behaviors. However, the contribution of the A2AR to the control of impulsive reward seeking remains unknown. Using mice that were exposed to differential reward of low rate (DRL) schedules during Pavlovian-conditioning, second-order schedule discrimination, and the 5-choice serial reaction time task (5-CSRTT), we demonstrate that deficits of A2AR function promote impulsive responses. Antagonism of the A2AR lowered ERK1 and ERK2 phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity during Pavlovian-conditioning and the 5-CSRTT...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28413458/mir-9-functions-as-a-tumor-inhibitor-of-cell-proliferation-in-epithelial-ovarian-cancer-through-targeting-the-sdf-1-cxcr4-pathway
#12
Lin He, Li Zhang, Mengfei Wang, Wenrong Wang
The current study aimed to investigate the potential role of miR-9 in the inhibition of ovarian cancer progression through the stromal cell-derived factor-1 (SDF-1)/ C-X-C chemokine receptor type 4 (CXCR4) pathway and to provide a theoretical basis for the diagnosis and treatment of ovarian cancer. Human ovarian cancer OVCAR-3 cells were transfected with miR-9 short hairpin RNA (shRNA). The effect of miR-9 on the mRNA expression levels of CXCR4 were analyzed using reverse transcription-quantitative polymerase chain reaction...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28406179/genetic-visualization-of-protein-interactions-harnessing-liquid-phase-transitions
#13
Taku Watanabe, Tatsuya Seki, Takashi Fukano, Asako Sakaue-Sawano, Satoshi Karasawa, Misaki Kubota, Hiroshi Kurokawa, Ken Inoue, Junichi Akatsuka, Atsushi Miyawaki
Protein-protein interactions (PPIs) are essential components of cellular function. Current fluorescence-based technologies to measure PPIs have limited dynamic range and quantitative reproducibility. Here, we describe a genetically-encoded PPI visualization system that harnesses the dynamics of condensed liquid-phase transitions to analyze protein interactions in living cells. The fluorescent protein Azami-Green and p62-PB1 domain when fused to PPI partners triggered a rapid concatenation/oligomerization process that drove the condensation of liquid-phase droplets for real-time analysis of the interaction with unlimited dynamic range in the fluorescence signal...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28400509/oncogene-kras-activates-fatty-acid-synthase-resulting-in-specific-erk-and-lipid-signatures-associated-with-lung-adenocarcinoma
#14
Arvin M Gouw, Livia S Eberlin, Katherine Margulis, Delaney K Sullivan, Georgia G Toal, Ling Tong, Richard N Zare, Dean W Felsher
KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been associated with altered glucose and glutamine metabolism. Here, we show that KRAS activates lipogenesis, and this activation results in distinct proteomic and lipid signatures. By gene expression analysis, KRAS is shown to be associated with a lipogenesis gene signature and specific induction of fatty acid synthase (FASN). Through desorption electrospray ionization MS imaging (DESI-MSI), specific changes in lipogenesis and specific lipids are identified...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28396345/the-ww-domain-of-the-scaffolding-protein-iqgap1-is-neither-necessary-nor-sufficient-for-binding-to-the-mapks-erk1-and-erk2
#15
A Jane Bardwell, Leonila Lagunes, Ronak Zebarjedi, Lee Bardwell
Mitogen-activated protein kinase (MAPK) scaffold proteins, such as IQ motif containing GTPase activating protein 1 (IQGAP1), are promising targets for novel therapies against cancer and other diseases. Such approaches require accurate information about which domains on the scaffold protein bind to the kinases in the MAPK cascade. Results from previous studies have suggested that the WW domain of IQGAP1 binds to the cancer-associated MAPKs ERK1 and ERK2, and that this domain might thus offer a new tool to selectively inhibit MAPK activation in cancer cells...
April 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28393304/lanthanum-chloride-precipitation-based-toxicoproteomic-analysis-of-3-monochloropropane-1-2-diol-toxicity-in-rat-kidney-reveals-involvement-of-extracellular-signal-regulated-kinase-2
#16
Axel Oberemm, Monique Braun, Stefanie Sawada, Mario Pink, Falko Frenzel, Christel Rozycki, Christine Meckert, Elke Zabinsky, Albert Braeuning, Alfonso Lampen
The heat-induced food contaminant 3-monochloropropane-1,2-diol (3-MCPD) and its fatty acid esters exert nephrotoxicity in rodents. Previous studies including a non-targeted toxicoproteomics approach using samples from a 28-day oral toxicity study in rats with 10 mg/kg body weight (b.w.) of 3-MCPD, an equimolar dose of 53 mg/kg b.w. 3-MCPD dipalmitate and a lower dose of 13.3 mg/kg b.w. of 3-MCPD dipalmitate, revealed substance-induced alterations in metabolic pathways, especially for glycolysis and energy metabolism...
April 9, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28380434/inos-derived-nitric-oxide-promotes-glycolysis-by-inducing-pyruvate-kinase-m2-nuclear-translocation-in-ovarian-cancer
#17
Linlin Li, Lingqun Zhu, Bingtao Hao, Wenwen Gao, Qianli Wang, Keyi Li, Meng Wang, Mengqiu Huang, Zhengjun Liu, Qiaohong Yang, Xiqing Li, Zhuo Zhong, Wenhua Huang, Guanghui Xiao, Yang Xu, Kaitai Yao, Qiuzhen Liu
Aerobic glycolysis is essential for tumor growth and survival. Activation of multiple carcinogenic signals contributes to metabolism reprogramming during malignant transformation of cancer. Recently nitric oxide has been noted to promote glycolysis but the mechanism remains elusive. We report here the dual role of nitric oxide in glycolysis: low/physiological nitric oxide (≤ 100 nM) promotes glycolysis for ATP production, oxidative defense and cell proliferation of ovary cancer cells, whereas excess nitric oxide (≥ 500 nM) inhibits it...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28359799/paxillin-and-embryonic-polyadenylation-binding-protein-epabp-engage-to-regulate-androgen-dependent-xenopus-laevis-oocyte-maturation-a-model-of-kinase-dependent-regulation-of-protein-expression
#18
Susanne U Miedlich, Manisha Taya, Melissa Rasar Young, Stephen R Hammes
Steroid-triggered Xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. We previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in Xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances Mos protein translation, ensued by Erk2 activation and Erk-dependent phosphorylation of paxillin on serine residues...
March 28, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28359774/trpv4-regulates-insulin-mrna-expression-and-ins-1e-cell-death-via-erk1-2-and-no-dependent-mechanisms
#19
M Billert, M Skrzypski, M Sassek, D Szczepankiewicz, T Wojciechowicz, S Mergler, M Z Strowski, K W Nowak
TRPV4 is a Ca(2+)-permeable, nonselective cation channel. Recently, TRPV4 was implicated in controlling peripheral insulin sensitivity, insulin secretion and apoptosis of pancreatic beta cells. Here, we characterize the role and potential mechanisms of TRPV4 in regulating insulin mRNA expression and cell death in insulin producing INS-1E cells and rat pancreatic islets. TRPV4 protein production was downregulated by siRNA. Intracellular calcium level was measured using Fluo-3 AM. Gene expression was studied by real-time PCR...
March 27, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28333195/genome-wide-genetic-analyses-highlight-mitogen-activated-protein-kinase-mapk-signaling-in-the-pathogenesis-of-endometriosis
#20
Outi Uimari, Nilufer Rahmioglu, Dale R Nyholt, Katy Vincent, Stacey A Missmer, Christian Becker, Andrew P Morris, Grant W Montgomery, Krina T Zondervan
STUDY QUESTION: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways...
April 1, 2017: Human Reproduction
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