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Cheng He, Ai-Yuan Chen, Hai-Xia Wei, Xiao-Shuang Feng, Hong-Juan Peng
The invasion of Toxoplasma gondii tachyzoites into the host cell results in extensive host cell signaling activation/deactivation that is usually regulated by the phosphorylation/dephosphorylation. To elucidate how T. gondii regulates host cell signal transduction, the comparative phosphoproteome of stable isotope labeling with amino acids in cell culture-labeled human foreskin fibroblast cells was analyzed. The cells were grouped (Light [L], Medium [M], and Heavy [H] groups) based on the labeling isotope weight and were infected with T...
July 2017: American Journal of Tropical Medicine and Hygiene
Hayato Ogura, Yuka Nagatake-Kobayashi, Jun Adachi, Takeshi Tomonaga, Naoya Fujita, Ryohei Katayama
ROS1 rearrangement is observed in 1-2% of non-small cell lung cancers (NSCLC). The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has induced marked tumour shrinkage in ROS1-rearranged cancers. However, emergence of acquired resistance to TKI is inevitable within a few years. Previous findings indicate that cabozantinib overcomes secondary mutation-mediated crizotinib-resistance in ROS1-fusion-positive cells. Here we attempted to establish cabozantinib-resistant cells by N-ethyl-N-nitrosourea mutagenesis screening using CD74-ROS1-expressing Ba/F3 cells...
July 17, 2017: Scientific Reports
Mercedes Cano, Antonio Ayala, Francesco Marotta, Sandro Argüelles
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives . Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review , we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA)...
July 14, 2017: Current Pharmaceutical Design
Jing Ren, Juan Mao, Cunwu Zuo, Alejandro Calderón-Urrea, Mohammed Mujitaba Dawuda, Xin Zhao, Xinwen Li, Baihong Chen
Drought stress is a major problem around the world and there is still little molecular mechanism about how fruit crops deal with moderate drought stress. Here, the physiological and phosphoproteomic responses of drought-sensitive genotype (M26) and drought-tolerant genotype (MBB) under moderate drought stress were investigated. Our results of the physiology analysis indicated that the MBB genotype could produce more osmosis-regulating substances. Furthermore, phosphoproteins from leaves of both genotypes under moderate drought stress were analyzed using the isobaric tags for relative and absolute quantification technology...
July 14, 2017: Molecular Genetics and Genomics: MGG
Xiangbo Xin, Xinfeng Liu, Xin Li, Xiangbin Ding, Shuping Yang, Congfei Jin, Guangpeng Li, Hong Guo
The biosafety of fat-1 transgenic cattle has been a focus of our studies since the first fat-1 transgenic cow was born. In this study, we used tandem mass tag labeling, TiO2 enrichment, and nanoscale liquid chromatography coupled with tandem mass spectrometry (nanol LC-MS/MS) to compare proteomic and phosphoproteomic profiling analyses of muscle between fat-1 transgenic cows and wild-type cows. A total of 1555 proteins and 900 phosphorylation sites in 159 phosphoproteins were identified in the profiling assessments, but only four differentially expressed proteins and nine differentially expressed phosphopeptides were detected in fat-1 transgenic cows relative to wild-type cows...
July 14, 2017: Transgenic Research
Paul M Epstein
No abstract text is available yet for this article.
July 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Ruijin Wang, Junbo Peng, Qing X Li, You-Liang Peng
Protein phosphorylation is known to regulate pathogenesis, mycelial growth, conidiation and stress response in Pyricularia oryzae However, phosphorylation mediated regulatory networks in the fungal pathogen remain largely to be uncovered. In this study, we identified 1621 phosphorylation sites of 799 proteins in mycelia of P. oryzae, including 899 new p-sites of 536 proteins and 47 new p-sites of 31 pathogenesis-relation proteins. From the sequences flanking the phosphorylation sites, 19 conserved phosphorylation motifs were identified...
July 13, 2017: Molecular & Cellular Proteomics: MCP
Didier Vertommen, Gaetan Herinckx, Nusrat Hussain, Fred Opperdoes, Kenneth B Storey, Mark H Rider
Mammalian hibernation is characterized by metabolic rate depression and a strong decrease in core body temperature. Brown adipose tissue (BAT), a thermogenic tissue that uses uncoupled mitochondrial respiration to generate heat instead of ATP, plays a major role in rewarming from deep torpor. In the present study we developed a label-free LC-MS strategy to investigate both differential protein expression and protein phosphorylation in BAT extracts from euthermic versus hibernating ground squirrels. In particular, we incorporated the filter-assisted sample preparation (FASP) protocol, which provides a more in-depth analysis compared with gel-based and other LC-MS proteomics approaches...
July 10, 2017: Physiological Genomics
Lindsay L Traeger, Grzegorz Sabat, Gregory A Barrett-Wilt, Gregg B Wells, Michael R Sussman
The electric eel (Electrophorus electricus) is unusual among electric fishes because it has three pairs of electric organs that serve multiple biological functions: For navigation and communication, it emits continuous pulses of weak electric discharge (<1 V), but for predation and defense, it intermittently emits lethal strong electric discharges (10 to 600 V). We hypothesized that these two electrogenic outputs have different energetic demands reflected by differences in their proteome and phosphoproteome...
July 2017: Science Advances
Yeunkum Lee, Doyoun Kim, Jae Ryun Ryu, Yinhua Zhang, Shinhyun Kim, Yoonhee Kim, Bokyoung Lee, Woong Sun, Kihoon Han
Actin dynamics is a critical mechanism underlying many cellular processes in neurons. The heteropentameric WAVE-regulatory complex (WRC), consisting of WAVE, CYFIP1/2, Nap, Abi, and HSPC300, is a key regulator of actin dynamics that activates the Arp2/3 complex to initiate actin polymerization and branching. The WRC is basally inactive because of intermolecular interactions among the components, which can be modulated by bindings of phospholipids and Rac1, and phosphorylations of WAVE and Abi. However, the phosphorylation of other components of WRC and their functional significance remain largely unknown...
August 16, 2017: Neuroreport
Maria Dermit, Arran Dokal, Pedro R Cutillas
Cells integrate extracellular signals into appropriate responses through a complex network of biochemical reactions driven by the activity of protein and lipid kinases, among other proteins. In order to understand this complexity, new approaches, both experimental and computational, have recently been developed with the aim to identify regulatory kinases and infer their activation status in the context of their signalling network. Here, we review such approaches with particular focus on those based on phosphoproteomics...
July 10, 2017: FEBS Letters
Yuanyuan Zhang, Yajie Zhang, Yonghao Yu
Insulin resistance is a hallmark of type 2 diabetes. Although multiple genetic and physiological factors interact to cause insulin resistance, deregulated signaling by phosphorylation is a common underlying mechanism. In particular, the specific phosphorylation-dependent regulatory mechanisms and signaling outputs of insulin is poorly understood in hepatocytes, which represents one of the most important insulin-responsive cell types. Using primary rat hepatocytes as a model system, we performed reductive di-methylation (ReDi)-based quantitative mass spectrometric analysis, and characterized the phosphoproteome that is regulated by insulin, as well as its key downstream kinases including Akt, mTORC1 and S6K...
July 9, 2017: Journal of Proteome Research
Sudhir Kumar, Manish Kumar, Roseleen Ekka, Jeffrey D Dvorin, Aditya S Paul, Anil K Madugundu, Tim Gilberger, Harsha Gowda, Manoj T Duraisingh, T S Keshava Prasad, Pushkar Sharma
Calcium Dependent Protein Kinases are key effectors of calcium signaling in malaria parasite. PfCDPK1 is critical for asexual development of Plasmodium falciparum, but its precise function and substrates remain largely unknown. Using a conditional knockdown strategy, we here establish that this kinase is critical for the invasion of host erythrocytes. Furthermore, using a multidisciplinary approach involving comparative phosphoproteomics we gain insights into the underlying molecular mechanisms. We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly...
July 5, 2017: Nature Communications
Kizhake V Soman, Susan J Stafford, Konrad Pazdrak, Zheng Wu, Xuemei Luo, Wendy I White, John E Wiktorowicz, William J Calhoun, Alexander Kurosky
Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered an important factor in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset...
July 5, 2017: Journal of Proteome Research
Elena Panizza, Rui M M Branca, Peter Oliviusson, Lukas M Orre, Janne Lehtiö
Protein phosphorylation is involved in the regulation of most eukaryotic cells functions and mass spectrometry-based analysis has made major contributions to our understanding of this regulation. However, low abundance of phosphorylated species presents a major challenge in achieving comprehensive phosphoproteome coverage and robust quantification. In this study, we developed a workflow employing titanium dioxide phospho-enrichment coupled with isobaric labeling by Tandem Mass Tags (TMT) and high-resolution isoelectric focusing (HiRIEF) fractionation to perform in-depth quantitative phosphoproteomics starting with a low sample quantity...
July 3, 2017: Scientific Reports
Edmund Wilkes, Pedro Casado, Vinothini Rajeeve, Pedro Rodriguez Cutillas
Cell survival is regulated by a signaling network driven by the activity of protein kinases; however, determining the contribution that each kinase in the network makes to such regulation remains challenging. Here, we report a computational approach that uses mass spectrometry-based phosphoproteomics data to rank protein kinases based on their contribution to cell regulation. We found that the scores returned by this algorithm, which we have termed Kinase Activity Ranking using Phosphoproteomics data (KARP), were a quantitative measure of the contribution that individual kinases make to the signaling output...
July 3, 2017: Molecular & Cellular Proteomics: MCP
Zaibao Zhang, Menghui Hu, Xiaobing Feng, Andong Gong, Lin Cheng, Hongyu Yuan
In flowering plants, anther development plays crucial role in sexual reproduction. Within the anther, microspore mother cells meiosis produces microspores, which further develop into pollen grains that play decisive role in plant reproduction. Previous studies on anther biology mainly focused on single gene functions relying on genetic and molecular methods. Recently, anther development has been expanded from multiple OMICS approaches like transcriptomics, proteomics/phosphoproteomics, and metabolomics. The development of proteomics techniques allowing increased proteome coverage and quantitative measurements of proteins which can characterize proteomes and their modulation during normal development, biotic and abiotic stresses in anther development...
June 30, 2017: Proteomics
Brendan L Powers, Mark C Hall
Inactivation of cyclin-dependent kinase (Cdk) and reversal of Cdk phosphorylation are universally required for mitotic exit. In budding yeast, Cdc14 is essential for both and thought to be the major Cdk-counteracting phosphatase. However, Cdc14 is not required for mitotic exit in many eukaryotes, despite highly conserved biochemical properties. The question of how similar enzymes could have such disparate influences on mitotic exit prompted us to re-examine the contribution of budding yeast Cdc14. Using an auxin-inducible degron, severe Cdc14 depletion had no effect on the kinetics of mitotic exit and bulk Cdk substrate dephosphorylation, but caused a cell separation defect and was ultimately lethal...
June 29, 2017: Journal of Cell Science
Bifan Chen, Leekyoung Hwang, William Ochowicz, Ziqing Lin, Tania M Guardado-Alvarez, Wenxuan Cai, Lichen Xiu, Kunal Dani, Cyrus Colah, Song Jin, Ying Ge
Phosphorylation plays pivotal roles in cellular processes and dysregulated phosphorylation is considered as an underlying mechanism in many human diseases. Top-down mass spectrometry (MS) analyzes intact proteins and provides a comprehensive analysis of protein phosphorylation. However, top-down MS-based phosphoproteomics is challenging due to the difficulty in enriching low abundance intact phosphoproteins as well as separating and detecting the enriched phosphoproteins from complex mixtures. Herein, we have designed and synthesized the next generation functionalized superparamagnetic cobalt ferrite (CoFe2O4) nanoparticles (NPs), and have further developed a top-down phosphoproteomics strategy coupling phosphoprotein enrichment enabled by the functionalized CoFe2O4 NPs with online liquid chromatography (LC)/MS/MS for comprehensive characterization of phosphoproteins...
June 1, 2017: Chemical Science
Sarah-Lena Offenburger, Dalila Bensaddek, Alejandro Brenes Murillo, Angus I Lamond, Anton Gartner
Asymmetric cell divisions are required for cellular diversity and defects can lead to altered daughter cell fates and numbers. In a genetic screen for C. elegans mutants with defects in dopaminergic head neuron specification or differentiation, we isolated a new allele of the transcription factor HAM-1 [HSN (Hermaphrodite-Specific Neurons) Abnormal Migration]. Loss of both HAM-1 and its target, the kinase PIG-1 [PAR-1(I)-like Gene], leads to abnormal dopaminergic head neuron numbers. We identified discrete genetic relationships between ham-1, pig-1 and apoptosis pathway genes in dopaminergic head neurons...
June 28, 2017: Scientific Reports
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