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https://www.readbyqxmd.com/read/28526413/tcr-crosslinking-promotes-crk-adaptor-protein-binding-to-tyrosine-phosphorylated-cd3%C3%AE-chain
#1
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Sigal Gelkop, Noah Isakov
T cell antigen receptor (TCR) binding of a peptide antigen presented by antigen-presenting cells (APCs) in the context of surface MHC molecules initiates signaling events that regulate T cell activation, proliferation and differentiation. A key event in the activation process is the phosphorylation of the conserved tyrosine residues within the CD3 chain immunoreceptor tyrosine-based activation motifs (ITAMs), which operate as docking sites for SH2 domain-containing effector proteins. Phosphorylation of the CD3ζ ITAMs renders the CD3 chain capable of binding the ζ-chain associated protein 70 kDa (ZAP70), a protein tyrosine kinase that is essential for T cell activation...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28521404/silencing-tak1-alters-gene-expression-signatures-in-bladder-cancer-cells
#2
Jimin Chen, Nan Zhang, Jiaming Wen, Zhewei Zhang
The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 (TAK1) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 (FGFR3) bladder cancer cells transfected with control siRNA or TAK1-specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28512623/ca-2-microdomains-in-t-lymphocytes
#3
REVIEW
Insa M A Wolf, Andreas H Guse
Early Ca(2+) signaling is characterized by occurrence of Ca(2+) microdomains formed by opening of single or clusters of Ca(2+) channels, thereby initiating first signaling and subsequently activating global Ca(2+) signaling mechanisms. However, only few data are available focusing on the first seconds and minutes of Ca(2+) microdomain formation and related signaling pathways in activated T-lymphocytes. In this review, we condense current knowledge on Ca(2+) microdomain formation in T-lymphocytes and early Ca(2+) signaling, function of Ca(2+) microdomains, and microdomain organization...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28496318/pri-microrna-124-rs531564-polymorphism-minor-allele-increases-the-risk-of-pulmonary-artery-hypertension-by-abnormally-enhancing-proliferation-of-pulmonary-artery-smooth-muscle-cells
#4
Quanzhong Li, Zongjie Qian, Linqing Wang
MicroRNA-124 (miR-124) has been reported to be downregulated in the cells exposed to hypoxia, which was confirmed in our study. We then used online microRNA target prediction tools to identify GRB2, SMAD5, and JAG1 as the candidate target genes of miR-124, and we next validated GRB2 as a direct gene by using luciferase reporter system. We also established the regulatory relationship between miR-124 and GRB2 by showing the negative linear relationship between GRB2 and miR-124 expression. Furthermore, we investigated the miR-124 and GRB2 expression levels of different genotypes including CC (n=30), GC (n=18), and GG (n=4), which supported the hypothesis that the presence of minor allele (C) of rs531564 polymorphism compromised the expression of miR-124...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28470949/loss-of-sh3gl2-promotes-the-migration-and-invasion-behaviours-of-glioblastoma-cells-through-activating-the-stat3-mmp2-signalling
#5
Yufu Zhu, Xiang Zhang, Lei Wang, Zhe Ji, Manyi Xie, Xinyu Zhou, Zhiyi Liu, Hengliang Shi, Rutong Yu
SH3GL2 (Src homology 3 (SH3) domain GRB2-like 2) is mainly expressed in the central nervous system and regarded as a tumour suppressor in human glioma. However, the molecular mechanism of the SH3GL2 protein involved in malignant behaviours of human glioma has not been elucidated. In this study, we tried to investigate the role of SH3GL2 in glioma cell migration and invasion and explore its underlined molecular mechanism. Firstly, we discovered that the protein level of SH3GL2 was widely decreased in the human glioma patients, especially in high-grade glioma tissues...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28455498/grb2-carboxyl-terminal-sh3-domain-can-bivalently-associate-with-two-ligands-in-an-sh3-dependent-manner
#6
Richa Arya, Rohit Singh Dangi, Pinakin K Makwana, Ambrish Kumar, Santosh Kumar Upadhyay, Monica Sundd
Src homology domain containing leukocyte protein of 65 kDa (SLP65), the growth factor receptor binding protein 2 (Grb2), and the guanine nucleotide exchange factor for the Rho family GTPases (Vav), self associate in unstimulated B cells as components of the preformed B cell receptor transducer module, in an SH3-dependent manner. The complex enables the B cell to promptly respond to BCR aggregation, resulting in signal amplification. It also facilitates Vav translocation to the membrane rafts, for activation...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28452363/mechanism-of-sos-pr-domain-autoinhibition-revealed-by-single-molecule-assays-on-native-protein-from-lysate
#7
Young Kwang Lee, Shalini T Low-Nam, Jean K Chung, Scott D Hansen, Hiu Yue Monatrice Lam, Steven Alvarez, Jay T Groves
The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition...
April 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28444820/casticin-impairs-cell-migration-and-invasion-of-mouse-melanoma-b16f10-cells-via-pi3k-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#8
Yung-Luen Shih, Hsiao-Min Chou, Hsiu-Chen Chou, Hsu-Feng Lu, Yung-Lin Chu, Hung-Sheng Shang, Jing-Gung Chung
Casticin, a polymethoxyflavone, is one of the major active components obtained from Fructus viticis, which have been shown to have anticancer activities including induce cell apoptosis in human cancer cells. The aim of this study was to investigate the molecular mechanisms by which casticin inhibits cell migration and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT assay and the results indicated that casticin decreased the total percentages of viable cells in dose-dependent manners...
April 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28436964/swell1-is-a-regulator-of-adipocyte-size-insulin-signalling-and-glucose-homeostasis
#9
Yanhui Zhang, Litao Xie, Susheel K Gunasekar, Dan Tong, Anil Mishra, William J Gibson, Chuansong Wang, Trevor Fidler, Brodie Marthaler, Aloysius Klingelhutz, E Dale Abel, Isaac Samuel, Jessica K Smith, Lei Cao, Rajan Sah
Adipocytes undergo considerable volumetric expansion in the setting of obesity. It has been proposed that such marked increases in adipocyte size may be sensed via adipocyte-autonomous mechanisms to mediate size-dependent intracellular signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich Repeat Containing protein family, is an essential component of a volume-sensitive ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented in hypertrophic murine and human adipocytes in the setting of obesity...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28426660/exhaustive-search-of-linear-information-encoding-protein-peptide-recognition
#10
Abdellali Kelil, Benjamin Dubreuil, Emmanuel D Levy, Stephen W Michnick
High-throughput in vitro methods have been extensively applied to identify linear information that encodes peptide recognition. However, these methods are limited in number of peptides, sequence variation, and length of peptides that can be explored, and often produce solutions that are not found in the cell. Despite the large number of methods developed to attempt addressing these issues, the exhaustive search of linear information encoding protein-peptide recognition has been so far physically unfeasible...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28422494/genetically-encoded-2-aryl-5-carboxytetrazoles-for-site-selective-protein-photo-cross-linking
#11
Yulin Tian, Marco Paolo Jacinto, Yu Zeng, Zhipeng Yu, Jun Qu, Wenshe R Liu, Qing Lin
The genetically encoded photo-cross-linkers promise to offer a temporally controlled tool to map transient and dynamic protein-protein interaction complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5-carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation into proteins via amber codon suppression in Escherichia coli and mammalian cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was found to give robust and site-selective photo-cross-linking reactivity in E...
May 3, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28420432/elevated-gab2-induces-tumor-growth-and-angiogenesis-in-colorectal-cancer-through-upregulating-vegf-levels
#12
Chenbo Ding, Junmin Luo, Xiaobo Fan, Longmei Li, Shanshan Li, Kunming Wen, Jihong Feng, Guoqiu Wu
BACKGROUND: Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves as a critical signaling amplifier downstream of tyrosine kinase receptors. Our previous study has shown that Gab2 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of Gab2 in CRC growth and angiogenesis remains unclear. METHODS: The expression of vascular endothelial growth factor (VEGF) in different colorectal tissues was detected by immunohistochemistry and qRT-PCR to evaluate its correlation with Gab2...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28417283/bis-anthracycline-wp760-abrogates-melanoma-cell-growth-by-transcription-inhibition-p53-activation-and-igf1r-downregulation
#13
Magdalena Olbryt, Aleksandra Rusin, Izabela Fokt, Anna Habryka, Patrycja Tudrej, Sebastian Student, Aleksander Sochanik, Rafał Zieliński, Waldemar Priebe
Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations...
April 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28412750/microrna-302c-3p-inhibits-renal-cell-carcinoma-cell-proliferation-by-targeting-grb2-associated-binding-2-gab2
#14
Dong-Hua Gu, Jia-Hui Mao, Xiao-Dong Pan, Hua Zhu, Xinfeng Chen, Bing Zheng, Yuxi Shan
The expression and biological function of Grb2-associated binding 2 (Gab2) in renal cell carcinoma (RCC) cells was tested here. We showed that Gab2 expression was significantly elevated in human RCC tissues and RCC cells. It was correlated with over-activation of Akt and downregulation of microRNA-302c-3p ("miR-302c-3p"), a putative Gab2-targeting microRNA. Knockdown of Gab2 inhibited Akt activation and 786-O RCC cell proliferation. Reversely, forced over-expression of Gab2 led to Akt hyper-activation to facilitate 786-O cell proliferation...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28374783/itraq-based-proteomic-analysis-of-porcine-kidney-epithelial-pk15-cells-infected-with-pseudorabies-virus
#15
Songbai Yang, Yue Pei, Ayong Zhao
Pseudorabies virus (PRV) is one of the most important pathogens of swine, resulting in severe economic losses to the pig industry. To improve our understanding of the host responses to PRV infection, we applied isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography-tandem mass spectrometry to quantitatively identify the differentially expressed cellular proteins in PRV-infected PK15 cells. In total, relative quantitative data were identified for 4333 proteins in PRV and mock- infected PK15 cells, among which 466 cellular proteins were differentially expressed, including 234 upregulated proteins and 232 downregulated proteins...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28361043/cleavage-of-grb2-associated-binding-protein-2-by-viral-proteinase-2a-during-coxsackievirus-infection
#16
Haoyu Deng, Gabriel Fung, Ye Qiu, Chen Wang, Jingchun Zhang, Zheng-Gen Jin, Honglin Luo
Coxsackievirus type B3 (CV-B3), an enterovirus associated with the pathogenesis of several human diseases, subverts, or employs the host intracellular signaling pathways to support effective viral infection. We have previously demonstrated that Grb2-associated binding protein 1 (GAB1), a signaling adaptor protein that serves as a platform for intracellular signaling assembly and transduction, is cleaved upon CV-B3 infection, resulting in a gain-of-pro-viral-function via the modification of GAB1-mediated ERK1/2 pathway...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28360125/cellular-levels-of-grb2-and-cytoskeleton-stability-are-correlated-in-a-neurodegenerative-scenario
#17
Piyali Majumder, Kasturi Roy, Brijesh Kumar Singh, Nihar Ranjan Jana, Debashis Mukhopadhyay
Alzheimer's disease (AD) manifests as neuronal loss. On the premise of Grb2 overexpression in AD mouse brain and brain tissues of AD patients, our study primarily focuses on the stability of cytoskeletal proteins in the context of degenerative AD-like conditions. Two predominant molecular features of AD, extracellular accumulation of β-amyloid oligomers and intracellular elevation of amyloid precursor protein intracellular domain levels, have been used to closely inspect the series of signalling events. In their presence, multiple signalling pathways involving ROCK and PAK1 proteins lead to disassembly of the cytoskeleton, and Grb2 partially counterbalances the cytoskeletal loss...
May 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28355572/precise-temporal-profiling-of-signaling-complexes-in-primary-cells-using-swath-mass-spectrometry
#18
Etienne Caron, Romain Roncagalli, Takeshi Hase, Witold E Wolski, Meena Choi, Marisa G Menoita, Stephane Durand, Antonio García-Blesa, Ivo Fierro-Monti, Tatjana Sajic, Moritz Heusel, Tobias Weiss, Marie Malissen, Ralph Schlapbach, Ben C Collins, Samik Ghosh, Hiroaki Kitano, Ruedi Aebersold, Bernard Malissen, Matthias Gstaiger
Spatiotemporal organization of protein interactions in cell signaling is a fundamental process that drives cellular functions. Given differential protein expression across tissues and developmental stages, the architecture and dynamics of signaling interaction proteomes is, likely, highly context dependent. However, current interaction information has been almost exclusively obtained from transformed cells. In this study, we applied an advanced and robust workflow combining mouse genetics and affinity purification (AP)-SWATH mass spectrometry to profile the dynamics of 53 high-confidence protein interactions in primary T cells, using the scaffold protein GRB2 as a model...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28333195/genome-wide-genetic-analyses-highlight-mitogen-activated-protein-kinase-mapk-signaling-in-the-pathogenesis-of-endometriosis
#19
Outi Uimari, Nilufer Rahmioglu, Dale R Nyholt, Katy Vincent, Stacey A Missmer, Christian Becker, Andrew P Morris, Grant W Montgomery, Krina T Zondervan
STUDY QUESTION: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways...
April 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28322937/snail-induced-epithelial-to-mesenchymal-transition-enhances-p-gp-mediated-multi-drug-resistance-in-hcc827-cells
#20
Takumi Tomono, Kentaro Yano, Takuo Ogihara
Overexpression and/or activation of P-glycoprotein (P-gp), which mediates efflux transport of various anti-cancer drugs in cancer cells, are associated with multi-drug resistance (MDR). On the other hand, malignant cancer cells frequently undergo epithelial-to-mesenchymal transition (EMT), thereby acquiring high migratory mobility and invasive ability. Snail is a transcriptional factor that represses multiple other factors, and its overexpression is a trigger of EMT. Since both P-gp and Snail are involved in malignant evolution of cancer, in this work, we evaluated whether or not EMT induced by overexpression of Snail influences P-gp expression and/or activity...
March 17, 2017: Journal of Pharmaceutical Sciences
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