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https://www.readbyqxmd.com/read/28819788/insulin-like-growth-factor-1-activates-different-catalytic-subunits-p110-of-pi3k-in-a-cell-type-dependent-manner-to-induce-lipogenesis-dependent-epithelial-mesenchymal-transition-through-the-regulation-of-adam10-and-adam17
#1
Ga Bin Park, Daejin Kim
The activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is critical for the induction of epithelial-mesenchymal transition (EMT) by growth factors, including insulin-like growth factor 1 (IGF-1). The activation of intracellular lipogenesis provides proliferative and survival signals for cancer cells. In this study, we investigated the connection between lipogenesis-related EMT processes and IGF-1-mediated PI3K p110 isoform activation in primary (SW480 cells) and metastatic (SW620) colon carcinoma cells...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28819423/reelin-promotes-adhesion-of-multiple-myeloma-cells-to-bone-marrow-stromal-cells-via-integrin-%C3%AE-1-signaling
#2
Liang Lin, Xinwei Zhang, Li Cao, Quanming An, Jie Hao, Yan Zhang, Rong Jin, Yingjun Chang, Xiaojun Huang, Jin Lu, Qing Ge
The close interaction between tumor cells and bone marrow stromal cells plays a crucial role in the tumorigenesis of multiple myeloma (MM). Reelin, an extracellular matrix protein, is found expressed in myeloma cells and is negatively associated with prognosis. We examined the role of Reelin in myeloma cell adhesion to bone marrow stromal cells and the signaling pathways involved. The results revealed that Reelin promoted the adhesion of myeloma cells to HS-5, a bone marrow stromal cell line, via the activation of β1 integrin...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28813645/lat-is-essential-for-the-mast-cell-stabilising-effect-of-thga-in-ige-mediated-mast-cell-activation
#3
Ji Wei Tan, Daud Ahmad Israf, Nur Fariesha Md Hashim, Yoke Kqueen Cheah, Hanis Hazeera Harith, Khozirah Shaari, Chau Ling Tham
Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28811826/anti-inflammatory-effect-of-piper-attenuatum-methanol-extract-in-lps-stimulated-inflammatory-responses
#4
You Jin Kim, Jeong Deok, Sunggyu Kim, Deok Hyo Yoon, Gi-Ho Sung, Adithan Aravinthan, Seungihm Lee, Mi-Nam Lee, Suntaek Hong, Jong-Hoon Kim, Young-Jin Son, Jae Youl Cho
Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28808303/nlrp3-inflammasome-activation-results-in-liver-inflammation-and-fibrosis-in-mice-infected-with-schistosoma-japonicum-in-a-syk-dependent-manner
#5
Ya-Qi Lu, Shan Zhong, Nan Meng, Yin-Ping Fan, Wang-Xian Tang
Granulomatous and fibrosing inflammation in response to soluble egg antigen (SEA) from Schistosoma japonicum (S. japonicum) is the main pathological process of S. japonicum infection. Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both in vivo and in vitro during S...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28804558/nadph-oxidase-2-inhibitor-diphenyleneiodonium-enhances-ros-independent-bacterial-phagocytosis-in-murine-macrophages-via-activation-of-the-calcium-mediated-p38-mapk-signaling-pathway
#6
Yuanfeng Zhu, Shijun Fan, Ning Wang, Xiaoli Chen, Yongjun Yang, Yongling Lu, Qian Chen, Jiang Zheng, Xin Liu
Activation of NADPH oxidase 2 (NOX2) triggers reactive oxygen species (ROS) generation, both of which are essential for robust microbial clearance by phagocytes. However, it is unknown whether inhibition of NOX2 activation or ROS generation affects cellular phagocytosis. Here, we found that the classic NOX2 inhibitor diphenyleneiodonium (DPI) induced uptake of E. coli by murine peritoneal macrophages through enhancing phagocytosis, and this effect was temperature-sensitive and attenuated by cytochalasin D as well as chemical inhibition of Syk and PLCγ, two downstream kinases involved in actin polymerization during phagocytosis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28794269/the-fc%C3%AE%C2%B5ri-signaling-cascade-and-integrin-trafficking-converge-at-patterned-ligand-surfaces
#7
Devin L Wakefield, David Holowka, Barbara Baird
We examined the spatial targeting of early and downstream signaling mediated by the IgE receptor (FcεRI) in RBL mast cells utilizing surface-patterned 2,4 dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge-concentrated for DNP-BSA...
August 9, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28791394/identification-of-key-genes-and-pathways-associated-with-classical-hodgkin-lymphoma-by-bioinformatics-analysis
#8
Zhixing Kuang, Li Guo, Xun Li
The current study aimed to explore the mechanisms associated with classic Hodgkin lymphoma (cHL) to identify novel diagnostic and therapeutic targets. The GES12453 microarray dataset was downloaded from the Gene Expression Omnibus database; the differentially expressed genes (DEGs) between cHL samples and normal B cell samples by were identified using the limma package. Gene ontology (GO) and pathway enrichment analysis of DEGs gene were performed. Furthermore, construction and analysis of protein‑protein interaction (PPI) network was performed, and co‑expression modules of DEGs were produced...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28791367/molecular-mechanisms-of-breast-cancer-metastasis-by-gene-expression-profile-analysis
#9
Tianying Zheng, Aijun Wang, Dongyan Hu, Yonggang Wang
Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software...
August 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28789968/b-cell-phenotypes-signaling-and-their-roles-in-secretion-of-antibodies-in-systemic-lupus-erythematosus
#10
Yoshiya Tanaka, Satoshi Kubo, Shigeru Iwata, Maiko Yoshikawa, Shingo Nakayamada
B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5(+) IgM memory B cells to CXCR3(+) class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features...
August 5, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28775078/tlr2-plays-a-key-role-in-platelet-hyperreactivity-and-accelerated-thrombosis-associated-with-hyperlipidemia
#11
Sudipta Biswas, Alejandro Zimman, Detao Gao, Tatiana Byzova, Eugene Podrez
Rationale: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. Objective: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to accumulation in the circulation of a specific group of oxidized phospholipids (oxPCCD36) that are ligands for the platelet pattern-recognition receptor CD36...
August 3, 2017: Circulation Research
https://www.readbyqxmd.com/read/28768156/the-syk-kinases-orchestrate-cerebellar-granule-cell-tangential-migration
#12
Aurélien Benon, Choua Ya, Laurent Martin, Chantal Watrin, Naura Chounlamountri, Iness Jaaoini, Jérôme Honnorat, Véronique Pellier-Monnin, Nelly Noraz
The tyrosine kinases of the Syk family are essential components of the well-characterized immunoreceptor ITAM-based signaling pathway. However, ITAM-based signaling typically does not function in isolation. Instead, it is enmeshed in the molecular network controlling cellular adhesion and chemotaxis. Consistent with the increasing number of data involving ITAM-bearing molecules in neuronal functions, we previously depicted a role for Syk kinases in the establishment of neuronal connectivity. In the developing cerebellum, we found that Syk is essentially expressed in the granule cells (GC) and more importantly, phosphorylated on tyrosine residues representative of an active form of the kinase in tangentially migrating GC...
July 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/28767218/selective-binders-of-the-tandem-sh2-domains-in-syk-and-zap-70-kinases-by-dna-programmed-spatial-screening
#13
Michaela Marczynke, Katharina Groeger, Oliver Seitz
Members of the Syk family of tyrosine kinases arrange Src homology 2 (SH2) domains in tandem to allow firm binding of immunoreceptor tyrosine-based interaction motifs (ITAMs). While the advantages provided by the bivalency enhanced interactions are evident, the impact on binding specificity is less clear. For example, the Spleen tyrosine kinase (Syk) and the Zeta-chain-associated protein kinase (ZAP-70) recognize the consensus sequence pYXXI/L(X)6-8 pYXXI/L with near identical nanomolar affinity. The non-discriminatory recognition on the one hand poses a specificity challenge for the design of sub-type selective protein binders and, on the other hand, raises the question as to how differential activation of Syk and ZAP-70 is ensured when both kinases are co-expressed...
August 2, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28760774/unperturbed-immune-function-despite-mutation-of-c-terminal-tyrosines-in-syk-previously-implicated-in-signaling-and-activity-regulation
#14
Vanessa Weis, Sebastian Königsberger, Susanne Amler, Jürgen Wienands, Friedemann Kiefer
The non-receptor tyrosine kinase Syk, a central regulator of immune cell differentiation and activation, is a promising drug target for treatment of leukemia, allergic and inflammatory diseases. The clinical failure of Syk inhibitors underscores the importance to understand the regulation of Syk function and activity.A series of previous studies emphasized the importance of three C-terminal tyrosines in Syk for kinase activity regulation, as docking sites for downstream effector molecules and for Ca(2+) mobilization...
July 31, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28754125/syk-inhibitors-in-clinical-development-for-hematological-malignancies
#15
REVIEW
Delong Liu, Aleksandra Mamorska-Dyga
Spleen tyrosine kinase (Syk) is a cytosolic non-receptor protein tyrosine kinase (PTK) and is mainly expressed in hematopoietic cells. Syk was recognized as a critical element in the B-cell receptor signaling pathway. Syk is also a key component in signal transduction from other immune receptors like Fc receptors and adhesion receptors. Several oral Syk inhibitors including fostamatinib (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659 are being assessed in clinical trials. The second generation compound, entospletinib, showed promising results in clinical trials against B-cell malignancies, mainly chronic lymphoid leukemia...
July 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28747804/differential-signalling-and-kinetics-of-neutrophil-extracellular-trap-release-revealed-by-quantitative-live-imaging
#16
Maarten van der Linden, Geertje H A Westerlaken, Michiel van der Vlist, Joris van Montfrans, Linde Meyaard
A wide variety of microbial and inflammatory factors induce DNA release from neutrophils as neutrophil extracellular traps (NETs). Consensus on the kinetics and mechanism of NET release has been hindered by the lack of distinctive methods to specifically quantify NET release in time. Here, we validate and refine a semi-automatic live imaging approach for quantification of NET release. Importantly, our approach is able to correct for neutrophil input and distinguishes NET release from neutrophil death by other means, aspects that are lacking in many NET quantification methods...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747380/identification-of-differentially-expressed-splice-variants-by-the-proteogenomic-pipeline-splicify
#17
Malgorzata A Komor, Thang Pham, Annemieke C Hiemstra, Sander R Piersma, Anne S Bolijn, Tim Schelfhorst, Pien M Delis-van Diemen, Marianne Tijssen, Robert P Sebra, Meredith Ashby, Gerrit A Meijer, Connie R Jimenez, Remond J A Fijneman
Proteogenomics, i.e. comprehensive integration of genomics and proteomics data, is a powerful approach identifying novel protein biomarkers. This is especially the case for proteins that differ structurally between disease and control conditions. As tumor development is associated with aberrant splicing, we focus on this rich source of cancer specific biomarkers. To this end, we developed a proteogenomic pipeline, Splicify, which is able to detect differentially expressed protein isoforms. Splicify is based on integrating RNA massive parallel sequencing data and tandem mass spectrometry proteomics data to identify protein isoforms resulting from differential splicing between two conditions...
July 26, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28744004/sirt1-negatively-regulates-fc%C3%AE%C2%B5ri-mediated-mast-cell-activation-through-ampk-and-ptp1b-dependent-processes
#18
Xian Li, Youn Ju Lee, Fansi Jin, Young Na Park, Yifeng Deng, Youra Kang, Ju Hye Yang, Jae-Hoon Chang, Dong-Young Kim, Jung-Ae Kim, Young-Chae Chang, Hyun-Jeong Ko, Cheorl-Ho Kim, Makoto Murakami, Hyeun Wook Chang
Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736554/differential-requirements-for-src-family-kinases-in-syk-or-zap70-mediated-slp-76-phosphorylation-in-lymphocytes
#19
Frank Fasbender, Maren Claus, Sabine Wingert, Mina Sandusky, Carsten Watzl
In a synthetic biology approach using Schneider (S2) cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736076/suppression-of-ige-mediated-mast-cell-activation-and-mouse-anaphylaxis-via-inhibition-of-syk-activation-by-8-formyl-7-hydroxy-4-methylcoumarin-4%C3%AE-8c
#20
Seung Taek Nam, Young Hwan Park, Hyun Woo Kim, Hyuk Soon Kim, Dajeong Lee, Min Bum Lee, Young Mi Kim, Wahn Soo Choi
Mast cells trigger IgE-mediated allergic reactions by releasing various allergic mediators. 8-Formyl-7-hydroxy-4-methylcoumarin, also called 4μ8C, was originally known as an inositol-requiring enzyme 1 (IRE1) suppressant, but no study has examined its relationship with mast cells and allergic diseases. Therefore, the purpose of this study was to determine whether 4μ8C is effective in suppressing allergic reactions in mast cells and in IgE-mediated allergic animal model. 4μ8C suppressed the degranulation of IgE-mediated mast cells (IC50=3...
July 20, 2017: Toxicology and Applied Pharmacology
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