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https://www.readbyqxmd.com/read/28938584/bmpr2-promotes-invasion-and-metastasis-via-the-rhoa-rock-limk2-pathway-in-human-osteosarcoma-cells
#1
Shidong Wang, Tingting Ren, Guangjun Jiao, Yi Huang, Xing Bao, Fan Zhang, Kuisheng Liu, Bingxin Zheng, Kunkun Sun, Wei Guo
Bone morphogenetic protein receptor 2 (BMPR2) has been identified in several types of cancer. However, its role in osteosarcoma is largely unknown. We systematically investigated the role of BMPR2 in osteosarcoma cell lines, human tissue samples and xenograft models. The relationship between BMPR2 expression and osteosarcoma patients' survival was investigated by bioinformatics and clinical data. Wound healing assay and transwell assay were used to detect the changes of cell migration and invasion ability after BMPR2 transfection...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936665/phosphoprotein-enrichment-from-tobacco-mature-pollen-crude-protein-extract
#2
Jan Fíla, David Honys
Protein phosphorylation was repeatedly shown to be the most dynamic post-translational modification mediated by a huge orchestra of protein kinases and phosphatases. Upon landing on a stigma, pollen grain dehydration and activation are accompanied by changes in protein phosphorylation together with the translation activation of stored mRNAs. To enable studies of the total phosphoproteome, it is usually necessary to apply various enrichment techniques. In this chapter, one of these protocols that worked previously well on tobacco mature pollen is presented in more detail...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28934028/toward-neuroproteomics-in-biological-psychiatry-a-systems-approach-unravels-okadaic-acid-induced-alterations-in-the-neuronal-phosphoproteome
#3
Joana Machado Oliveira, Cristóvão B da Cruz E Silva, Thorsten Müller, Tânia Soares Martins, Marta Cova, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Neuroproteomics is an evolving field of postgenomic medicine, highlighting the convergence of psychiatry/neurology and proteomics, yet compared with neurogenetics, it has received little attention. This study in rat primary neuronal cultures provides an example of a neuroproteomic approach relevant to the study of psychiatric disease pathophysiology, focusing on Alzheimer's disease. In this context, okadaic acid (OA) is routinely used in experimental designs to investigate phosphorylation-mediated events. It is a potent protein phosphatase (PP) inhibitor, particularly of PP1 and PP2A...
September 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28933595/phosphoproteome-based-kinase-activity-profiling-reveals-the-critical-role-of-map2k2-and-plk1-in-neuronal-autophagy
#4
Lei-Lei Chen, Yong-Bo Wang, Ju-Xian Song, Wan-Kun Deng, Jia-Hong Lu, Li-Li Ma, Chuan-Bin Yang, Min Li, Yu Xue
Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signalling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B)...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28923824/snapin-promotes-hiv-1-transmission-from-dendritic-cells-by-dampening-tlr8-signaling
#5
Elham Khatamzas, Madeleine Maria Hipp, Daniel Gaughan, Tica Pichulik, Alasdair Leslie, Ricardo A Fernandes, Daniele Muraro, Sarah Booth, Kieran Zausmer, Mei-Yi Sun, Benedikt Kessler, Sarah Rowland-Jones, Vincenzo Cerundolo, Alison Simmons
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4(+) T cells in DCs, including the dynein motor protein Snapin...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28920954/p38-mapk-mk2-dependent-phosphorylation-controls-cytotoxic-ripk1-signalling-in-inflammation-and%C3%A2-infection
#6
Manoj B Menon, Julia Gropengießer, Jessica Fischer, Lena Novikova, Anne Deuretzbacher, Juri Lafera, Hanna Schimmeck, Nicole Czymmeck, Natalia Ronkina, Alexey Kotlyarov, Martin Aepfelbacher, Matthias Gaestel, Klaus Ruckdeschel
Receptor-interacting protein kinase-1 (RIPK1), a master regulator of cell fate decisions, was identified as a direct substrate of MAPKAP kinase-2 (MK2) by phosphoproteomic screens using LPS-treated macrophages and stress-stimulated embryonic fibroblasts. p38(MAPK)/MK2 interact with RIPK1 in a cytoplasmic complex and MK2 phosphorylates mouse RIPK1 at Ser321/336 in response to pro-inflammatory stimuli, such as TNF and LPS, and infection with the pathogen Yersinia enterocolitica. MK2 phosphorylation inhibits RIPK1 autophosphorylation, curtails RIPK1 integration into cytoplasmic cytotoxic complexes, and suppresses RIPK1-dependent apoptosis and necroptosis...
September 18, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28916722/phosphoproteomics-reveals-that-glycogen-synthase-kinase-3-phosphorylates-multiple-splicing-factors-and-is-associated-with-alternative-splicing
#7
Mansi Y Shinde, Simone Sidoli, Katarzyna Kulej, Michael J Mallory, Caleb M Radens, Amanda Reicherter, Rebecca L Myers, Yoseph Barash, Kristen W Lynch, Benjamin A Garcia, Peter S Klein
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif (pS/pTXXXS/T), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry (MS) techniques to analyze the repertoire of GSK-3-dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ~2...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915803/tartrate-resistant-acid-phosphatase-trap-acp5-promotes-metastasis-related-properties-via-tgf%C3%AE-2-t%C3%AE-r-and-cd44-in-mda-mb-231-breast-cancer-cells
#8
Anja Reithmeier, Elena Panizza, Michael Krumpel, Lukas M Orre, Rui M M Branca, Janne Lehtiö, Barbro Ek-Rylander, Göran Andersson
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. METHODS: MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28915586/hepatitis-c-virus-core-protein-targets-4e-bp1-expression-and-phosphorylation-and-potentiates-myc-induced-liver-carcinogenesis-in-transgenic-mice
#9
Cosette Abdallah, Charlène Lejamtel, Nassima Benzoubir, Serena Battaglia, Nazha Sidahmed-Adrar, Christophe Desterke, Matthieu Lemasson, Arielle R Rosenberg, Didier Samuel, Christian Bréchot, Delphine Pflieger, François Le Naour, Marie-Françoise Bourgeade
Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915437/temporal-characterization-of-the-non-structural-adenovirus-type-2-proteome-and-phosphoproteome-using-high-resolving-mass-spectrometry
#10
Malin Källsten, Arina Gromova, Hongxing Zhao, Alberto Valdés, Anne Konzer, Ulf Pettersson, Sara Bergström Lind
The proteome and phosphoproteome of non-structural proteins of Adenovirus type 2 (Ad2) were time resolved using a developed mass spectrometry approach. These proteins are expressed by the viral genome and important for the infection process, but not part of the virus particle. We unambiguously confirm the existence of 95% of the viral proteins predicted to be encoded by the viral genome. Most non-structural proteins peaked in expression at late time post infection. We identified 27 non-redundant sites of phosphorylation on seven different non-structural proteins...
September 12, 2017: Virology
https://www.readbyqxmd.com/read/28888781/siglec-8-is-an-activating-receptor-mediating-%C3%AE-2-integrin-dependent-function-in-human-eosinophils
#11
Daniela J Carroll, Jeremy A O'Sullivan, David B Nix, Yun Cao, Michael Tiemeyer, Bruce S Bochner
BACKGROUND: Siglec-8 is a CD33 subfamily cell surface receptor that is selectively expressed on human eosinophils. Following cytokine-priming, Siglec-8 mAb or glycan ligand binding causes eosinophil apoptosis associated with reactive oxygen species (ROS) production. Most CD33-related Siglecs function as inhibitory receptors, but the ability of Siglec-8 to stimulate eosinophil ROS production and apoptosis suggests that Siglec-8 may instead function as an activating receptor. OBJECTIVE: To determine the role of IL-5 priming and to identify the signaling molecules involved in Siglec-8 function for human eosinophils...
September 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28883432/quantitative-phosphoproteomic-analysis-reveals-key-mechanisms-of-cellular-proliferation-in-liver-cancer-cells
#12
Bo Zhu, Quanze He, Jingjing Xiang, Fang Qi, Hao Cai, Jun Mao, Chunhua Zhang, Qin Zhang, Haibo Li, Lu Lu, Ting Wang, Wenbo Yu
Understanding the mechanisms of uncontrolled proliferation in cancer cells provides valuable insights into tumor development and is benefit for discovering efficient methods in cancer treatment. In this study, we identified and quantified 2,057 phosphoproteins and 9,824 unique phosphosites in three liver cell lines with high (QGY, Hep3B) and low (L02) proliferative potentials and disclosed the wide variations in phosphorylation sites and levels among them. We found that the number of identified phosphoproteins and phosphosites in these cells were negatively correlated with their proliferative abilities...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882890/c-terminal-phosphorylation-of-nav1-5-impairs-fgf13-dependent-regulation-of-channel-inactivation
#13
Sophie Burel, Fabien C Coyan, Maxime Lorenzini, Matthew R Meyer, Cheryl F Lichti, Joan H Brown, Gildas Loussouarn, Flavien Charpentier, Jeanne M Nerbonne, R Reid Townsend, Lars S Maier, Céline Marionneau
Voltage-gated Na(+) (NaV) channels are key regulators of myocardial excitability, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent alterations in NaV1.5 channel inactivation are emerging as a critical determinant of arrhythmias in heart failure. However, the global native phosphorylation pattern of NaV1.5 subunits associated with these arrhythmogenic disorders, and the associated channel regulatory defects remain unknown. Here, we undertook phosphoproteomic analyses to identify and quantify in situ the phosphorylation sites in the NaV1...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28879772/brain-membrane-proteome-and-phosphoproteome-reveal-molecular-basis-associating-with-nursing-and-foraging-behaviors-of-honeybee-workers
#14
Bin Han, Yu Fang, Mao Feng, Han Hu, Yue Hao, Chuan Ma, Xinmei Huo, Lifeng Meng, Xufeng Zhang, Fan Wu, Jianke Li
The brain is a vital organ in regulating complex social behaviors of honeybees including learning and memory. Knowledge of how brain membrane proteins and their phosphorylation underlie the age-related behavioral polyethism is still lacking. A hitherto age-resolved brain membrane proteome and phosphoproteome were reported in adult worker bees from two strains of honeybee (Apis mellifera ligustica): Italian bee (ITB) and Royal Jelly bee (RJB), a line selected from ITB for increased RJ outputs over 4 decades...
September 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28878229/hydrogen-bond-based-smart-polymer-for-highly-selective-and-tunable-capture-of-multiply-phosphorylated-peptides
#15
Guangyan Qing, Qi Lu, Xiuling Li, Jing Liu, Mingliang Ye, Xinmiao Liang, Taolei Sun
Multisite phosphorylation is an important and common mechanism for finely regulating protein functions and subsequent cellular responses. However, this study is largely restricted by the difficulty to capture low-abundance multiply phosphorylated peptides (MPPs) from complex biosamples owing to the limitation of enrichment materials and their interactions with phosphates. Here we show that smart polymer can serve as an ideal platform to resolve this challenge. Driven by specific but tunable hydrogen bonding interactions, the smart polymer displays differential complexation with MPPs, singly phosphorylated and non-modified peptides...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28877958/proline-dependent-and-basophilic-kinases-phosphorylate-human-trpc6-at-serine-14-to-control-channel-activity-through-increased-membrane-expression
#16
Henning Hagmann, Nicole Mangold, Markus M Rinschen, Tim Koenig, Karl Kunzelmann, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Signaling via the transient receptor potential (TRP) ion channel C6 plays a pivotal role in hereditary and sporadic glomerular kidney disease. Several studies have identified gain-of-function mutations of TRPC6 and report induced expression and enhanced channel activity of TRPC6 in association with glomerular diseases. Interfering with TRPC6 activity may open novel therapeutic pathways. TRPC6 channel activity is controlled by protein expression and stability as well as intracellular trafficking. Identification of regulatory phosphorylation sites in TRPC6 and corresponding protein kinases is essential to understand the regulation of TRPC6 activity and may result in future therapeutic strategies...
September 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28874695/deep-phospho-and-phosphotyrosine-proteomics-identified-active-kinases-and-phosphorylation-networks-in-colorectal-cancer-cell-lines-resistant-to-cetuximab
#17
Yuichi Abe, Maiko Nagano, Takahisa Kuga, Asa Tada, Junko Isoyama, Jun Adachi, Takeshi Tomonaga
Abnormality in cellular phosphorylation is closely related to oncogenesis. Thus, kinase inhibitors, especially tyrosine kinase inhibitors (TKIs), have been developed as anti-cancer drugs. Genomic analyses have been used in research on TKI sensitivity, but some types of TKI resistance have been unclassifiable by genomic data. Therefore, global proteomic analysis, especially phosphotyrosine (pY) proteomic analysis, could contribute to predict TKI sensitivity and overcome TKI-resistant cancer. In this study, we conducted deep phosphoproteomic analysis to select active kinase candidates in colorectal cancer intrinsically resistant to Cetuximab...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870897/phosphoproteomic-analysis-identifies-signaling-pathways-regulated-by-curcumin-in-human-colon-cancer-cells
#18
Tatsuhiro Sato, Yutaka Higuchi, Yoshio Shibagaki, Seisuke Hattori
BACKGROUND: Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. MATERIALS AND METHODS: Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28866816/distinctively-expressed-cytokines-by-three-different-inflammation-cells-and-their-interaction-with-keratinocytes-in-wound-healing
#19
Jingwen Wang, Xusheng Wang, Haiyan Chen, Jianjun Liu, Edward E Tredget, Yaojiong Wu
Inflammatory cells exert crucial influence on wound healing, while exploration is still desired to get further insight into the key factors that promote the process. In the present study, we performed comparative microarray data analysis of the three types of inflammatory cells isolated from skin wounds and focused on differentially expressed secreted factors. Gene Ontology enrichment and receptor analysis indicated that 11 genes of secreted factors in Ly6C(+) inflammatory macrophages and 27 genes of secreted factors in neutrophils exhibited higher (≥ 5-fold) expression, and all these factors were considered as candidates with potentially important role in keratinocyte activation...
September 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28860483/selective-lrrk2-kinase-inhibition-reduces-phosphorylation-of-endogenous-rab10-and-rab12-in-human-peripheral-mononuclear-blood-cells
#20
Kenneth Thirstrup, Justus C Dächsel, Felix S Oppermann, Douglas S Williamson, Garrick P Smith, Karina Fog, Kenneth V Christensen
Genetic variation in the leucine-rich repeat kinase 2 (LRRK2) gene is associated with risk of familial and sporadic Parkinson's disease (PD). To support clinical development of LRRK2 inhibitors as disease-modifying treatment in PD biomarkers for kinase activity, target engagement and kinase inhibition are prerequisite tools. In a combined proteomics and phosphoproteomics study on human peripheral mononuclear blood cells (PBMCs) treated with the LRRK2 inhibitor Lu AF58786 a number of putative biomarkers were identified...
August 31, 2017: Scientific Reports
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