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Cynthia de la Fuente, Chelsea Pinkham, Deemah Dabbagh, Brett Beitzel, Aura Garrison, Gustavo Palacios, Kimberley Alex Hodge, Emanuel F Petricoin, Connie Schmaljohn, Catherine E Campbell, Aarthi Narayanan, Kylene Kehn-Hall
[This corrects the article DOI: 10.1371/journal.pone.0191983.].
2018: PloS One
Shuping Yang, Xin Li, Xinfeng Liu, Xiangbin Ding, Xiangbo Xin, Congfei Jin, Sheng Zhang, Guangpeng Li, Hong Guo
MSTN -encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis...
February 16, 2018: Oncotarget
Alexander Hogrebe, Louise von Stechow, Dorte B Bekker-Jensen, Brian T Weinert, Christian D Kelstrup, Jesper V Olsen
Comprehensive mass spectrometry (MS)-based proteomics is now feasible, but reproducible quantification remains challenging, especially for post-translational modifications such as phosphorylation. Here, we compare the most popular quantification techniques for global phosphoproteomics: label-free quantification (LFQ), stable isotope labeling by amino acids in cell culture (SILAC) and MS2 - and MS3 -measured tandem mass tags (TMT). In a mixed species comparison with fixed phosphopeptide ratios, we find LFQ and SILAC to be the most accurate techniques...
March 13, 2018: Nature Communications
Marina E Borisova, Andrea Voigt, Maxim A X Tollenaere, Sanjeeb Kumar Sahu, Thomas Juretschke, Nastasja Kreim, Niels Mailand, Chunaram Choudhary, Simon Bekker-Jensen, Masato Akutsu, Sebastian A Wagner, Petra Beli
Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway...
March 9, 2018: Nature Communications
Tanveer S Batth, Moreno Papetti, Anamarija Pfeiffer, Maxim A X Tollenaere, Chiara Francavilla, Jesper V Olsen
Despite its low cellular abundance, phosphotyrosine (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)-initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1 and identified more than 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules...
March 6, 2018: Cell Reports
Maren Mönnich, Louise Borgeskov, Loretta Breslin, Lis Jakobsen, Michaela Rogowski, Canan Doganli, Jacob M Schrøder, Johanne B Mogensen, Louise Blinkenkjær, Lea M Harder, Emma Lundberg, Stefan Geimer, Søren T Christensen, Jens S Andersen, Lars A Larsen, Lotte B Pedersen
The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling...
March 6, 2018: Cell Reports
Alireza Azimi, Stefano Caramuta, Brinton Seashore-Ludlow, Johan Boström, Jonathan L Robinson, Fredrik Edfors, Rainer Tuominen, Kristel Kemper, Oscar Krijgsman, Daniel S Peeper, Jens Nielsen, Johan Hansson, Suzanne Egyhazi Brage, Mikael Altun, Mathias Uhlen, Gianluca Maddalo
Novel therapies are undergoing clinical trials, for example, the Hsp90 inhibitor, XL888, in combination with BRAF inhibitors for the treatment of therapy-resistant melanomas. Unfortunately, our data show that this combination elicits a heterogeneous response in a panel of melanoma cell lines including PDX-derived models. We sought to understand the mechanisms underlying the differential responses and suggest a patient stratification strategy. Thermal proteome profiling (TPP) identified the protein targets of XL888 in a pair of sensitive and unresponsive cell lines...
March 5, 2018: Molecular Systems Biology
Johnny R Ramroop, Mark N Stein, Justin M Drake
Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach...
2018: Frontiers in Oncology
Niya Gowthami, B Sunitha, Manish Kumar, T S Keshava Prasad, N Gayathri, B Padmanabhan, M M Srinivas Bharath
In eukaryotes, mitochondrial complex I (NADH: ubiquinone oxidoreductase; CI) is central to oxidative phosphorylation (OXPHOS). Mammalian CI is a 45 subunit complex that forms supercomplexes with other OXPHOS complexes. Since CI defects are associated with aging and neurodegeneration, it is pertinent to understand its structure-function relationship. Although genetic mutations could lower CI activity causing mitochondrial dysfunction in several pathologies, post-translational modifications (PTMs) have emerged as a key mechanism contributing to altered CI activity...
February 27, 2018: Journal of Chemical Neuroanatomy
Erxu Pi, Chengmin Zhu, Wei Fan, Yingying Huang, Liqun Qu, Yangyang Li, Qinyi Zhao, Feng Ding, Lijuan Qiu, Huizhong Wang, B W Poovaiah, Liqun Du
Salinity causes osmotic stress to crops and limits their productivity. To understand the mechanism underlying soybean salt tolerance, proteomics approach was used to identify phosphoproteins altered by NaCl treatment. Results revealed that 412 of the 4698 quantitatively analyzed phosphopeptides were significantly up-regulated upon salt treatment, including a phosphopeptide covering the serine 59 in the transcription factor GmMYB173. Our data showed that GmMYB173 is one of the three MYB proteins differentially phosphorylated upon salt treatment, and a substrate of the casein kinase-II...
March 1, 2018: Molecular & Cellular Proteomics: MCP
Raghuveera Kumar Goel, Marta Paczkowska, Juri Reimand, Scott Napper, Kiven Erique Lukong
SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites), also known as PTK 70 (Protein tyrosine kinase 70), is a non-receptor tyrosine kinase that belongs to the BRK family of kinases (BFKs). To date less is known about the cellular role of SRMS primarily due to the unidentified substrates or signaling intermediates regulated by the kinase. In this study, we used phosphotyrosine antibody-based immunoaffinity purification in large-scale label-free quantitative phosphoproteomics to identify novel candidate substrates of SRMS...
March 1, 2018: Molecular & Cellular Proteomics: MCP
Golam Jalal Ahammed
No abstract text is available yet for this article.
February 13, 2018: Current Protein & Peptide Science
Yuehan Pang, Xin Zhou, Yaling Chen, Jinsong Bao
Protein phosphorylation plays important roles in regulation of various molecular events such as plant growth and seed development. However, its involvement in starch biosynthesisis less understood. Here, a comparative phosphoproteomic analysis of two indica rice cultivars during grain development was performed. A total of 2079 and 2434 phosphopeptides from 1273 and 1442 phosphoproteins were identified, covering 2441 and 2808 phosphosites in indica rice 9311 and Guangluai4 (GLA4), respectively. Comparative analysis identified 303 differentially phosphorylated peptides, and 120 and 258 specifically phosphorylated peptides in 9311 and GLA4, respectively...
February 27, 2018: Journal of Agricultural and Food Chemistry
Anna Chorzalska, Nagib Ahsan, R Shyama Prasad Rao, Karim Roder, Xiaoqing Yu, John Morgan, Alexander Tepper, Steven Hines, Peng Zhang, Diana O Treaba, Ting C Zhao, Adam J Olszewski, John Reagan, Olin Liang, Philip A Gruppuso, Patrycja M Dubielecka
The introduction of tyrosine kinase inhibitors (TKI) has transformed chronic myeloid leukemia (CML) into a chronic disease with long-term survival exceeding 85%. However, resistance of CML stem cells to TKI may contribute to the 50% relapse rate observed after TKI discontinuation in molecular remission. We previously described a model of resistance to imatinib mesylate (IM), in which K562 cells cultured in high concentrations of imatinib mesylate showed reduced Bcr-Abl1 protein and activity levels while maintaining proliferative potential...
February 27, 2018: Molecular Oncology
Pavithra Rajagopalan, Vishalakshi Nanjappa, Krishna Patel, Ankit P Jain, Kiran K Mangalaparthi, Arun H Patil, Bipin Nair, Premendu P Mathur, T S Keshava Prasad, Joseph A Califano, David Sidransky, Harsha Gowda, Aditi Chatterjee
Smoking is the leading cause of preventable death worldwide. Though cigarette smoke is an established cause of head and neck cancer (including oral cancer), molecular alterations associated with chronic cigarette smoke exposure are poorly studied. To understand the signaling alterations induced by chronic exposure to cigarette smoke, we developed a cell line model by exposing normal oral keratinocytes to cigarette smoke for a period of 12 months. Chronic exposure to cigarette smoke resulted in increased cellular proliferation and invasive ability of oral keratinocytes...
February 26, 2018: Journal of Cell Communication and Signaling
Filip Mundt, Sandeep Rajput, Shunqiang Li, Kelly V Ruggles, Arshag D Mooradian, Philipp Mertins, Michael A Gillette, Karsten Krug, Zhanfang Guo, Jeremy Hoog, Petra Erdmann-Gilmore, Tina Primeau, Shixia Huang, Dean P Edwards, Xiaowei Wang, Xuya Wang, Emily Kawaler, D R Mani, Karl R Clauser, Feng Gao, Jingqin Luo, Sherri R Davies, Gary L Johnson, Kuan-Lin Huang, Christopher J Yoon, Li Ding, David Fenyö, Matthew J Ellis, R Reid Townsend, Jason M Held, Steven A Carr, Cynthia X Ma
Activation of phosphoinositide 3-kinase (PI3K) signaling is frequently observed in triple-negative breast cancer (TNBC), yet PI3K inhibitors have shown limited clinical activity. To investigate intrinsic and adaptive mechanisms of resistance, we analyzed a panel of patient-derived xenograft models of TNBC with varying responsiveness to buparlisib, a pan-PI3K inhibitor. In a subset of patient-derived xenografts, resistance was associated with incomplete inhibition of PI3K signaling and upregulated MAPK/MEK signaling in response to buparlisib...
February 22, 2018: Cancer Research
Liangliang Ren, Chaoying Li, Youliang Wang, Yan Teng, Huichuan Sun, Baocai Xing, Xiao Yang, Ying Jiang, Fuchu He
Aberrant kinases contribute to cancer survival and proliferation. Here, we quantitatively characterized phosphoproteomic changes in an HBx-transgenic mouse model of hepatocellular carcinoma (HCC) using high-resolution mass spectrometry, profiled 22,539 phosphorylation sites on 5,431 proteins. Utilizing a strategy to interpret kinase-substrate relations in HCC and to uncover predominant kinases in tumors, our results, revealed elevated kinase activities of Src family kinases (SFKs), PKCs, MAPKs, and ROCK2 in HCC, representatives of which were further validated in cell models and clinical HBV-positive HCC samples...
February 22, 2018: Molecular & Cellular Proteomics: MCP
Matthew J Berberich, Joao A Paulo, Robert A Everley
Protein phosphorylation is critically important for many cellular processes, including progression through the cell cycle, cellular metabolism and differentiation. The addition of isobaric labeling, e.g., Tandem Mass Tags (TMT), to phosphoproteomics workflows enables both relative and absolute quantitation of these phosphorylation events. Traditional TMT workflows identify peptides using fragment ions at the MS2 level and quantify reporter ions at the MS3 level. However, in addition to the TMT reporter ions, MS3 spectra also include fragment ions which can be used to identify peptides...
February 20, 2018: Journal of Proteome Research
Hwee Tong Tan, Maxey Ching Ming Chung
In this communication, we present the phosphoproteome changes in an isogenic pair of colorectal cancer cell lines, viz., the poorly metastatic HCT-116 and the highly metastatic derivative E1, upon stathmin-1 knockdown. The aim was to better understand how the alterations of the phosphoproteins in these cells are involved in cancer metastasis. After the phospho-peptides were enriched using the TiO2 HAMMOC approach, comparative proteomics analysis was carried out using SWATH-MS. Following bioinformatics analysis using MarkerView and OneOmics platforms, we identified a list of regulated phosphoproteins that may play a potential role in signaling, maintenance of cytoskeletal structure, and focal adhesion...
February 20, 2018: Proteomics
Ulrich Baumgartner, Fabienne Berger, Ali Hashemi Gheinani, Sabrina Sofia Burgener, Katia Monastyrskaya, Erik Vassella
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease...
February 19, 2018: Molecular Cancer
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