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https://www.readbyqxmd.com/read/29018805/insight-into-the-selectivity-of-the-g7-18nate-inhibitor-peptide-for-the-grb7-sh2-domain-target
#1
Gabrielle M Watson, William A H Lucas, Menachem J Gunzburg, Jacqueline A Wilce
Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28993193/%C3%AE-lipoic-acid-inhibits-human-lung-cancer-cell-proliferation-through-grb2-mediated-egfr-downregulation
#2
Lan Yang, Ya Wen, Guoqing Lv, Yuntao Lin, Junlong Tang, Jingxiao Lu, Manqiao Zhang, Wen Liu, Xiaojuan Sun
BACKGROUND: Alpha lipoic acid (α -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, α -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of α -LA on non-small cell lung cancer (NSCLC) development remain unclear. METHODS: The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after α -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28978467/m-%C3%A2-tuberculosis-initiated-human-mannose-receptor-signaling-regulates-macrophage-recognition-and-vesicle-trafficking-by-fcr%C3%AE-chain-grb2-and-shp-1
#3
Murugesan V S Rajaram, Eusondia Arnett, Abul K Azad, Evelyn Guirado, Bin Ni, Abigail D Gerberick, Li-Zhen He, Tibor Keler, Lawrence J Thomas, William P Lafuse, Larry S Schlesinger
Despite its prominent role as a C-type lectin (CTL) pattern recognition receptor, mannose receptor (MR, CD206)-specific signaling molecules and pathways are unknown. The MR is highly expressed on human macrophages, regulating endocytosis, phagocytosis, and immune responses and mediating Mycobacterium tuberculosis (M.tb) phagocytosis by human macrophages, thereby limiting phagosome-lysosome (P-L) fusion. We identified human MR-associated proteins using phosphorylated and non-phosphorylated MR cytoplasmic tail peptides...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28973902/drk-mediated-signaling-to-rho-kinase-is-required-for-anesthesia-resistant-memory-in-drosophila
#4
Vasileia Kotoula, Anastasios Moressis, Ourania Semelidou, Efthimios M C Skoulakis
Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in Drosophila remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28964849/grb2-regulates-the-proliferation-of-hematopoietic-stem-and-progenitors-cells
#5
Catherine Frelin, Yishai Ofran, Julie Ruston, Michal Hayun, Yael Derdikman, Yasmine Khier, Kinneret Rozales, Benjamin Brenner, Norman Iscove, Tony Pawson, Igal Louria-Hayon
Although Hematopoietic Stem and Progenitor Cell (HSPC) proliferation, survival and expansion have been shown to be supported by the cooperative action of different cytokines, little is known about the intracellular signaling pathways that are activated by cytokines upon binding to their receptors. Our study showed that Growth factor receptor-bound protein 2 (Grb2) mRNAs are preferentially expressed in HSC compared to progenitors and differentiated cells of the myeloid and erythroid lineages. Conditional deletion of Grb2 induced a rapid decline of erythroid and myeloid progenitors and a progressive decline of HSC numbers in steady state conditions...
September 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28951535/dimerization-of-the-adaptor-gads-facilitates-antigen-receptor-signaling-by-promoting-the-cooperative-binding-of-gads-to-the-adaptor-lat
#6
Sigalit Sukenik, Maria P Frushicheva, Cecilia Waknin-Lellouche, Enas Hallumi, Talia Ifrach, Rose Shalah, Dvora Beach, Reuven Avidan, Ilana Oz, Evgeny Libman, Ami Aronheim, Oded Lewinson, Deborah Yablonski
The accurate assembly of signalosomes centered on the adaptor protein LAT (linker of activated T cells) is required for antigen receptor signaling in T cells and mast cells. During signalosome assembly, members of the growth factor receptor-bound protein 2 (Grb2) family of cytosolic adaptor proteins bind cooperatively to LAT through interactions with its phosphorylated tyrosine (pTyr) residues. We demonstrated the Src homology 2 (SH2) domain-mediated dimerization of the Grb2 family member, Grb2-related adaptor downstream of Shc (Gads)...
September 26, 2017: Science Signaling
https://www.readbyqxmd.com/read/28938536/integrating-omics-data-and-protein-interaction-networks-to-prioritize-driver-genes-in-cancer
#7
Tiejun Zhang, Di Zhang
Although numerous approaches have been proposed to discern driver from passenger, identification of driver genes remains a critical challenge in the cancer genomics field. Driver genes with low mutated frequency tend to be filtered in cancer research. In addition, the accumulation of different omics data necessitates the development of algorithmic frameworks for nominating putative driver genes. In this study, we presented a novel framework to identify driver genes through integrating multi-omics data such as somatic mutation, gene expression, and copy number alterations...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936468/gfp-grb2-translocation-assay-using-high-content-imaging-to-screen-for-modulators-of-egfr-signaling
#8
Julia Petschnigg, Robin Ketteler
High-content screening is a useful tool to understand complex cellular processes and to identify genes, proteins or small molecule compounds that modulate such pathways. High-content assays monitor the function of a protein or pathway by visualizing a change in an image-based readout, such as a change in the localization of a reporter protein. Examples of this can be the translocation of a fluorescently tagged protein from the cytoplasm to the nucleus or to the plasma membrane. One protein that is known to undergo such translocation is the Growth Factor Receptor-bound protein 2 (GRB2) that is recruited to the plasma membrane upon stimulation of a growth factor receptor and subsequently undergoes internalization...
September 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28930697/overexpression-of-muc1-and-genomic-alterations-in-its-network-associate-with-prostate-cancer-progression
#9
Xiaozeng Lin, Yan Gu, Anil Kapoor, Fengxiang Wei, Tariq Aziz, Diane Ojo, Yanzhi Jiang, Michael Bonert, Bobby Shayegan, Huixiang Yang, Khalid Al-Nedawi, Pierre Major, Damu Tang
We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN(-/-) mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n=300), testing (n=185), and validation (n=194) cohort...
September 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28912526/mpzl1-forms-a-signalling-complex-with-grb2-adaptor-and-ptpn11-phosphatase-in-her2-positive-breast-cancer-cells
#10
Alice Beigbeder, François J M Chartier, Nicolas Bisson
HER2/ErbB2 is overexpressed in a significant fraction of breast tumours and is associated with a poor prognosis. The adaptor protein GRB2 interacts directly with activated HER2 and is sufficient to transmit oncogenic signals. However, the consequence of HER2 activation on global GRB2 signalling networks is poorly characterized. We performed GRB2 affinity purification combined with mass spectrometry analysis of associated proteins in a HER2+ breast cancer model to delineate GRB2-nucleated protein interaction networks...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898437/regulation-of-fibroblast-growth-factor-8-fgf8-in-chicken-embryonic-stem-cells-differentiation-into-spermatogonial-stem-cells
#11
Man Wang, Chen Zhang, Chuanli Huang, Shaoze Cheng, Nana He, Yilin Wang, Mahmoud F Ahmed, Ruifeng Zhao, Jing Jin, Qisheng Zuo, Yani Zhang, Bichun Li
Fibroblast growth factors (FGFs) are essential in regulating the formation of spermatogonial stem cells (SSCs). Here, we explored the effect of FGF8 on chicken SSCs formation by knockdown or overexpression of FGF8 in chicken embryonic stem cells (ESCs) both in vitro and in vivo. Our results showed that knockdown of FGF8 could facilitate the differentiation of ESCs into SSCs, overexpression of FGF8 could promote PGCs self-renewal, inhibit SSCs formation. This study further revealed the positive correlation between the expression level of FGF8 and MAPK/ERK signal...
September 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28893350/knockdown-of-gab1-inhibits-cellular-proliferation-migration-and-invasion-in-human-oral-squamous-carcinoma-cells
#12
Luyong Xu, Jie Li, Zheng Kuang, Yan Kuang, Hong Wu
Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is to be responsiblefor aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion and cell growth of OSCC cell lines SCC15 and SCC25. We found Gab1 was over-expressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion...
September 6, 2017: Oncology Research
https://www.readbyqxmd.com/read/28889064/spiroplasma-eriocheiris-induces-mouse-3t6-swiss-albino-cell-apoptosis-that-associated-with-the-infection-mechanism
#13
Libo Hou, Wei Gu, Huanxi Zhu, Wei Yao, Wen Wang, Qingguo Meng
Spiroplasma eriocheiris is a novel pathogen similar to the Spiroplasma mirum and also had an ability to infect the newborn mice and caused cataract. Our study was designed to study how S. eriocheiris infects mouse 3T6-Swiss albino cells and to elucidate the cellular molecular pathogenesis of Spiroplasma. FCM analysis and MTT analysis clearly shown that S. eriocheiris could induce 3T6 cell apoptosis and cause cell viability decreased seriously. Immunofluorescence experiments and TEM analysis shown that S. eriocheiris can invade 3T6 cells and form typical inclusion bodies and exhibit vacuolization in vitro...
September 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28877990/grb2-mediated-recruitment-of-usp9x-to-lat-enhances-themis-stability-following-thymic-selection
#14
Anne Garreau, Gaëtan Blaize, Jérémy Argenty, Nelly Rouquié, Audrey Tourdès, Stephen A Wood, Abdelhadi Saoudi, Renaud Lesourne
Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4(+)CD8(+) double-positive thymocytes and their commitment to the CD4(+)CD8(-) single-positive stage are impaired in Themis(-/-) mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28864021/the-core-transcriptome-of-mammalian-placentas-and-the-divergence-of-expression-with-placental-shape
#15
Don L Armstrong, Michael R McGowen, Amy Weckle, Priyadarshini Pantham, Jason Caravas, Dalen Agnew, Kurt Benirschke, Sue Savage-Rumbaugh, Eviatar Nevo, Chong J Kim, Günter P Wagner, Roberto Romero, Derek E Wildman
INTRODUCTION: The placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved. METHOD: Using RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades. RESULTS: We identified a set of 115 core genes which is expressed (FPKM ≥10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1)...
September 2017: Placenta
https://www.readbyqxmd.com/read/28855353/met-grb2-signaling-associated-complexes-correlate-with-oncogenic-met-signaling-and-sensitivity-to-met-kinase-inhibitors
#16
Matthew A Smith, Thomas Licata, Aliya Lakhani, Marileila Varella-Garcia, Hans-Ulrich Schildhaus, Vincent Vuaroqueaux, Balazs Halmos, Alain Borczuk, Y Ann Chen, Ben C Creelan, Theresa A Boyle, Eric B Haura
PURPOSE: Targeting MET in cancer is hampered by lack of diagnostics that accurately reflect high MET signaling and dependence. We hypothesized that assays reflecting MET signaling associated protein complexes could redefine tumors dependent on MET and could add additional precision beyond genomic assessments. EXPERIMENTAL DESIGN: We utilized biochemical approaches, cellular viability studies and proximity ligation assays to assess MET dependence. We examined MET signaling complexes in lung cancer patient specimens (N=406) and patient-derived xenograft models of solid tumors (N=308)...
August 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28846982/mir-200a-modulates-tgf-%C3%AE-1-induced-endothelial-to-mesenchymal-shift-via-suppression-of-grb2-in-haecs
#17
Hao Zhang, Jianguo Hu, Liming Liu
Endothelial-mesenchymal transition (EndMT) is closely associated with embryogenesis, injury restitution, tissue neogenesis, tumor progressions and viscera fibrosis. EndMT may occur in the proximal tubular endothelial cells, inducing fibroblasts to produce matrix and then accelerating the process of cardiac fibrosis. Transforming growth factor-β1 (TGF-β1), a profibrotic cytokine, was recently shown to be a crucial trigger of EndMT in tubular endothelial cells. Increasing evidence suggests that growth factor receptor-bound 2 (GRB2) dysfunction affects fibrocytes; thus, GRB2 may be a novel target for treating fibrosis...
August 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28842433/multicohort-analysis-reveals-baseline-transcriptional-predictors-of-influenza-vaccination-responses
#18
(no author information available yet)
Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies...
August 25, 2017: Science Immunology
https://www.readbyqxmd.com/read/28794017/differential-recruitment-of-e3-ubiquitin-ligase-complexes-regulates-ret-isoform-internalization
#19
Brandy D Hyndman, Mathieu J F Crupi, Susan Peng, Leslie N Bone, Aisha N Rekab, Eric Y Lian, Simona M Wagner, Costin N Antonescu, Lois M Mulligan
The RET receptor tyrosine kinase is implicated in normal development and cancer. RET is expressed as two isoforms, RET9 and RET51, with unique C-terminal tail sequences that recruit distinct protein complexes to mediate signals. Upon activation, RET isoforms are internalized with distinct kinetics, suggesting differences in regulation. Here, we demonstrate that RET9 and RET51 differ in their abilities to recruit E3 ubiquitin ligases to their unique C-termini. RET51, but not RET9, interacts with, and is ubiquitylated by CBL, which is recruited through interactions with the GRB2 adaptor protein...
October 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28791340/grb2-associated-binder-2-expression-and-its-roles-in-uveal-melanoma-invasion
#20
Meiling Chen, Yuehua Li, Xiuning Sun, Baogang Zhang, Wei Li, Shuxiao Wang, Xuetao Zhu, Feng Li, Lihong Shi
Uveal melanoma (UM) is characterized by high metastasis and poor prognosis. A more improved understanding of the metastatic mechanism in UM cells is essential for the design of molecular therapy. Grb2‑associated binder 2 (Gab2) has been reported to serve important roles in the progression of various types of human cancer. However, the role of Gab2 in the migration and invasion of UM remains unclear. The present study sought to further assess the expression of Gab2 in UM and the role of Gab2 in the invasion of UM cells...
October 2017: Molecular Medicine Reports
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