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https://www.readbyqxmd.com/read/27923225/integrin-%C3%AE-iib%C3%AE-3-dependent-erk-signaling-is-regulated-by-src-and-rho-kinases-in-both-leu33-and-pro33-polymorphic-isoforms
#1
Khon C Huynh, Thi-Hiep Nguyen, Dinh Chuong Pham, Huong T T Nguyen, Toi Van Vo, Marianna Gyenes, Volker R Stoldt
Platelet integrin αIIbβ3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbβ3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings...
December 7, 2016: Acta Haematologica
https://www.readbyqxmd.com/read/27914516/leukotriene-b4-induces-emt-and-vimentin-expression-in-panc-1-pancreatic-cancer-cells-involvement-of-blt2-via-erk2-activation
#2
You Ri Kim, Mi Kyung Park, Gyeong Jin Kang, Hyun Ji Kim, Eun Ji Kim, Hyun Jung Byun, Moo-Yeol Lee, Chang Hoon Lee
Leukotriene B4 (LTB4) is a leukocyte chemoattractant and plays a major role controlling inflammatory responses including pancreatitis. LTB4 is known to be correlated with cancer progression. LTB4 induces keratin phosphorylation and reorganization by activating extracellular regulated kinase (ERK) in PANC-1 pancreatic cancer cell lines. However, the role of LTB4 in epithelial mesenchymal transition (EMT) and vimentin expression in pancreatic cancer cells is unknown. We examined whether LTB4 induces EMT and vimentin expression by Western blot, si-RNA, and RT-PCR...
December 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27890652/inhibition-of-erk-mapk-suppresses-avian-leukosis-virus-subgroup-a-and-b-replication
#3
Manman Dai, Min Feng, Ming Liao, Weisheng Cao
We have previously shown that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway contributes to subgroup J avian leukosis virus (ALV-J) replication and tumorigenicity. However, a role for ERK/MAPK signaling in ALV-A and ALV-B replication is unknown. In this study we successfully constructed and recovered a recombinant form of ALV-A strain GD13-1 which showed similarities in growth to the parental wild type virus in vitro. ALV subgroups J, A or B all triggered ERK2 activation in primary CEF cells...
November 24, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27878277/synthetic-paclitaxel-octreotide-conjugate-reverses-the-resistance-of-paclitaxel-in-a2780-taxol-ovarian-cancer-cell-line
#4
Yang Shen, Xiao-Yu Zhang, Xi Chen, Li-Li Fan, Mu-Lan Ren, Yong-Ping Wu, Kenneth Chanda, Shi-Wen Jiang
The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27860455/papaverine-sensitive-phosphodiesterase-activity-is-measured-in-bovine-spermatozoa
#5
A Bergeron, A Hébert, C Guillemette, A Laroche, M-P Poulin, J P Aragon, P Leclerc, R Sullivan, P Blondin, C Vigneault, F J Richard
Cyclic adenosine monophosphate (cAMP) plays a crucial role as a signaling molecule for capacitation, motility, and acrosome reaction in mammalian spermatozoa. It is well-known that cAMP degradation by phosphodiesterase (PDE) enzyme has a major impact on sperm functions. This study was undertaken to characterize cAMP-PDE activity in bovine spermatozoa. Total cAMP-PDE activity in cauda epididymal and ejaculated spermatozoa was 543.2 ± 49.5 and 1252.6 ± 86.5 fmoles/min/10(6) spermatozoa, respectively. Using different family-specific PDE inhibitors, we showed that in cauda epididymal and ejaculated spermatozoa, the major cAMP-PDE activity was papaverine-sensitive (44...
November 16, 2016: Andrology
https://www.readbyqxmd.com/read/27857998/a-parp1-erk2-synergism-is-required-for-stimulation-induced-expression-of-immediate-early-genes
#6
M Cohen-Armon
A PARP1-Erk2 synergism was required to generate synaptic long-term potentiation in the CA3-CA1 hippocampal connections. This molecular mechanism was associated with the recently identified pivotal role of polyADP-ribosylation in learning. High frequency electrical stimulation of cortical and hippocampal neurons induced binding of phosphorylated Erk2 (transported into the nucleus) to the nuclear protein PARP1. PARP1-Erk2 binding induced PARP1 activation and polyADP-ribosylation of its prominent substrate, linker histone H1...
2016: Gene & Translational Bioinformatics
https://www.readbyqxmd.com/read/27846317/ras-mitogen-activated-protein-kinase-signal-is-required-for-enhanced-pd-l1-expression-in-human-lung-cancers
#7
Hidetoshi Sumimoto, Atsushi Takano, Koji Teramoto, Yataro Daigo
Ectopic programmed cell death ligand 1 (PD-L1) expression in non-small cell lung cancers (NSCLCs) is related to immune evasion by cancer, and it is a molecular target of immune checkpoint therapies. Although some altered signals in NSCLCs are responsible for ectopic PD-L1 expression, the precise mechanisms remain obscure. Because we found a higher frequency of EGFR/KRAS mutations in NSCLC cell lines with high PD-L1 expression (p < 0.001), we evaluated the relationships between downstream signals and PD-L1 expression, particularly in three KRAS-mutant adenocarcinoma cell lines...
2016: PloS One
https://www.readbyqxmd.com/read/27827993/hydrostatic-compress-force-enhances-the-viability-and-decreases-the-apoptosis-of-condylar-chondrocytes-through-integrin-fak-erk-pi3k-pathway
#8
Dandan Ma, Xiaoxing Kou, Jing Jin, Taotao Xu, Mengjie Wu, Liquan Deng, Lusi Fu, Yi Liu, Gang Wu, Haiping Lu
Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal-regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading...
November 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27822540/identification-of-novel-host-interactors-of-effectors-secreted-by-salmonella-and-citrobacter
#9
Ryan L Sontag, Ernesto S Nakayasu, Roslyn N Brown, George S Niemann, Michael A Sydor, Octavio Sanchez, Charles Ansong, Shao-Yeh Lu, Hyungwon Choi, Dylan Valleau, Karl K Weitz, Alexei Savchenko, Eric D Cambronne, Joshua N Adkins
Many pathogenic bacteria of the family Enterobacteriaceae use type III secretion systems to inject virulence proteins, termed "effectors," into the host cell cytosol. Although host-cellular activities of several effectors have been demonstrated, the function and host-targeted pathways of most of the effectors identified to date are largely undetermined. To gain insight into host proteins targeted by bacterial effectors, we performed coaffinity purification of host proteins from cell lysates using recombinant effectors from the Enterobacteriaceae intracellular pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium...
July 2016: MSystems
https://www.readbyqxmd.com/read/27815160/expression-and-regulation-of-prolactin-like-protein-messenger-rna-in-undifferentiated-chicken-granulosa-cells
#10
Shenqiang Hu, Raj Duggavathi, David Zadworny
Prolactin-like protein (PRL-L; LOC417800) is a homolog of PRL in non-mammalian vertebrates and can act as a functional ligand of PRL receptor (PRLR). Despite its widespread expression in extrapituitary tissues, mechanisms of regulation of PRL-L in the chicken ovary remain unknown. In this study, we first examined PRL-L expression in chicken ovarian developing follicles. PRL-L transcript levels were highest (P<0.05) in follicular walls of <2mm follicles and progressively declined during follicle maturation...
January 1, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27812285/a-multifaceted-role-for-myd88-dependent-signaling-in-progression-of-murine-mammary-carcinoma
#11
Mary J Higgins, Antonio Serrano, Kofi Y Boateng, Victoria A Parsons, Tiffany Phuong, Alyssa Seifert, Jacob M Ricca, Kyle C Tucker, Alec S Eidelman, Maureen A Carey, Robert A Kurt
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal-regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C-C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27802129/cpeb4-is-regulated-during-cell-cycle-by-erk2-cdk1-mediated-phosphorylation-and-its-assembly-into-liquid-like-droplets
#12
Jordina Guillén-Boixet, Víctor Buzon, Xavier Salvatella, Raúl Méndez
The four members of the vertebrate CPEB family of RNA-binding proteins share similar RNA-binding domains by which they regulate the translation of CPE-containing mRNAs, thereby controlling cell cycle and differentiation or synaptic plasticity. However, the N-terminal domains of CPEBs are distinct and contain specific regulatory post-translational modifications that presumably differentially integrate extracellular signals. Here we show that CPEB4 activity is regulated by ERK2- and Cdk1-mediated hyperphosphorylation...
November 1, 2016: ELife
https://www.readbyqxmd.com/read/27796752/synaptic-erk2-phosphorylates-and-regulates-metabotropic-glutamate-receptor-1-in-vitro-and-in-neurons
#13
Ju Hwan Yang, Li-Min Mao, Eun Sang Choe, John Q Wang
A synaptic pool of extracellular signal-regulated kinases (ERK) controls synaptic transmission, although little is known about its underlying signaling mechanisms. Here, we found that synaptic ERK2 directly binds to postsynaptic metabotropic glutamate receptor 1a (mGluR1a). This binding is direct and the ERK-binding site is located in the intracellular C-terminus (CT) of mGluR1a. Parallel with this binding, ERK2 phosphorylates mGluR1a at a cluster of serine residues in the distal part of mGluR1a-CT. In rat cerebellar neurons, ERK2 interacts with mGluR1a at synaptic sites, and active ERK constitutively phosphorylates mGluR1a under normal conditions...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27793200/subcellular-localisation-of-pmek-has-a-different-prognosis-in-locally-advanced-head-and-neck-cancer-treated-with-concomitant-radiochemotherapy
#14
J Gomez-Millan, B Pajares, L Perez-Villa, A Carnero, M Alvarez, V De Luque, F Rivas, J M Trigo, M D Toledo, E Alba, J A Medina
BACKGROUND: MEK1 (MAP2K1) and MEK2 (MAP2K2) are closely related dual-specificity protein kinases which function by phosphorylating both serine/threonine and tyrosine residues of their substrates ERK1 and ERK2, controlling fundamental cellular processes that include cell growth and proliferation. To investigate the prognostic significance of pMEK expression in the nucleus and cytoplasm among patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy. METHODS: Immunohistochemistry was performed on the retrieved archival tissue of 96 patients to detect pMEK, p53 and Ki-67...
October 28, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27791265/glul-promotes-cell-proliferation-in-breast-cancer
#15
Yanyan Wang, Shaohua Fan, Jun Lu, Zifeng Zhang, Dongmei Wu, Zhiyong Wu, Yuanlin Zheng
Glutamate-ammonia ligase (GLUL) belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the breast cancer patients was associated with larger tumor size and higher level of HER2 expression. In addition, GLUL was heterogeneously expressed in various breast cancer cells. The mRNA and protein expression levels of GLUL in SK-BR-3 cells were obviously higher than that in the other types of breast cancer cells...
October 28, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27780852/high-throughput-screening-identifies-mir-451-as-a-pleiotropic-modulator-that-suppresses-gastric-cancer-metastasis
#16
Wendao You, Liang Xu, Xing Zhang, Huan Zou, Dongtao Shi, Hanshuo Zhang, Juan Li, Weichang Chen, Rui Li
MicroRNAs (miRNAs) are globally dysregulated in human carcinomas. However, the specific miRNAs that mediate gastric cancer metastasis have not been identified. We identified 100 miRNAs that are dysregulated in gastric cancer and used a self-assembled cell microarray method to systematically evaluate their capacity to regulate cell migration. MiR-451, which is down-regulated in human gastric cancer samples, potently modulated multiple metastatic phenotypes including cell migration, invasion, proliferation, and epithelial-mesenchymal transition...
October 25, 2016: Journal of Laboratory Automation
https://www.readbyqxmd.com/read/27760319/phenotypic-characterization-of-a-comprehensive-set-of-mapk1-erk2-missense-mutants
#17
Lisa Brenan, Aleksandr Andreev, Ofir Cohen, Sasha Pantel, Atanas Kamburov, Davide Cacchiarelli, Nicole S Persky, Cong Zhu, Mukta Bagul, Eva M Goetz, Alex B Burgin, Levi A Garraway, Gad Getz, Tarjei S Mikkelsen, Federica Piccioni, David E Root, Cory M Johannessen
Tumor-specific genomic information has the potential to guide therapeutic strategies and revolutionize patient treatment. Currently, this approach is limited by an abundance of disease-associated mutants whose biological functions and impacts on therapeutic response are uncharacterized. To begin to address this limitation, we functionally characterized nearly all (99.84%) missense mutants of MAPK1/ERK2, an essential effector of oncogenic RAS and RAF. Using this approach, we discovered rare gain- and loss-of-function ERK2 mutants found in human tumors, revealing that, in the context of this assay, mutational frequency alone cannot identify all functionally impactful mutants...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27739308/critical-role-of-the-secondary-binding-pocket-in-modulating-enzymatic-activity-of-dusp5-towards-phosphorylated-erks
#18
Marat R Talipov, Jaladhi Nayak, Michael Lepley, Robert D Bongard, Daniel S Sem, Ramani Ramchandran, Rajendra Rathore
DUSP5 is an inducible nuclear dual-specificity phosphatase that specifically interacts with and deactivates extracellular signal-regulated kinases ERK1 and ERK2, which are responsible for cell proliferation, differentiation, and survival. The phosphatase domain (PD) of DUSP5 has unique structural features absent in other nuclear DUSPs, such as presence of a secondary anion-binding site in the proximity to the reaction center and a glutamic acid E264 positioned next to the catalytic cysteine C263, as well as a remote intra-molecular disulfide linkage...
October 14, 2016: Biochemistry
https://www.readbyqxmd.com/read/27738173/opposing-effects-of-elk-1-multisite-phosphorylation-shape-its-response-to-erk-activation
#19
Anastasia Mylona, Francois-Xavier Theillet, Charles Foster, Tammy M Cheng, Francesc Miralles, Paul A Bates, Philipp Selenko, Richard Treisman
Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of the transcriptional activation domain (TAD) of Elk-1 by the protein kinase ERK at multiple sites potentiates recruitment of the Mediator transcriptional coactivator complex and transcriptional activation, but the roles of individual phosphorylation events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 phosphorylation proceeds at markedly different rates at eight TAD sites in vitro, which we classified as fast, intermediate, and slow...
October 14, 2016: Science
https://www.readbyqxmd.com/read/27732676/bacterial-expression-purification-and-in-vitro-phosphorylation-of-full-length-ribosomal-s6-kinase-2-rsk2
#20
Darkhan Utepbergenov, Paulina M Hennig, Urszula Derewenda, Mykhaylo V Artamonov, Avril V Somlyo, Zygmunt S Derewenda
Ribosomal S6 kinases (RSK) play important roles in cell signaling through the mitogen-activated protein kinase (MAPK) pathway. Each of the four RSK isoforms (RSK1-4) is a single polypeptide chain containing two kinase domains connected by a linker sequence with regulatory phosphorylation sites. Here, we demonstrate that full-length RSK2-which is implicated in several types of cancer, and which is linked to the genetic Coffin-Lowry syndrome-can be overexpressed with high yields in Escherichia coli as a fusion with maltose binding protein (MBP), and can be purified to homogeneity after proteolytic removal of MBP by affinity and size-exclusion chromatography...
2016: PloS One
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