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https://www.readbyqxmd.com/read/29678287/novel-mechanisms-of-g-protein-coupled-receptors-functions-at-1-angiotensin-receptor-acts-as-a-signaling-hub-and-focal-point-of-receptor-cross-talk
#1
REVIEW
András D Tóth, Gábor Turu, László Hunyady, András Balla
AT1 angiotensin receptor (AT1 R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1 R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT1 R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29676784/expression-and-characterisation-of-%C3%AE-v%C3%AE-5-integrin-on-intestinal-macrophages
#2
Ashok K Kumawat, Chen Yu, Elizabeth A Mann, Anika Schridde, Silvia C Finnemann, Allan McI Mowat
Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here we show for the first time that mature intestinal macrophages in mouse colon and small intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodelling of the extracellular matrix. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29672153/p21-activated-kinase4-in-pancreatic-acini-is-activated-by-gi-hormones-growth-factors-by-novel-signaling-and-is-needed-to-stimulate-secretory-growth-cascades
#3
Irene Ramos-Alvarez, Robert T Jensen
p21-activated kinases(PAKs) are highly conserved serine/threonine protein kinases, which are divided into two groups:Group-I(PAKs1-3) and Group-II(PAKs4-6). In various tissues, Group-II PAKs play important roles in cytoskeletal dynamics, cell growth as well as neoplastic development/progression. However, little is known about Group-II PAKs role in a number of physiological events including their ability to be activated by gastrointestinal(GI) hormones/neurotransmitters/growth-factors(GFs). We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/GFs to activate Group-II-PAKs and the signaling cascades involved...
April 19, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29669810/structural-insights-into-the-mechanism-of-action-of-a-biparatopic-anti-her2-antibody
#4
Vaheh Oganesyan, Li Peng, Jared S Bee, John Li, Samuel R Perry, Frank Comer, Linda Xu, Kimberly Cook, Kannaki Senthil, Lori Clarke, Kim Rosenthal, Chanshou Gao, Melissa Damschroder, Herren Wu, William F Dall'Acqua
Pathways of human EGF receptors are activated upon ligand dependent or independent homo or heterodimerization and their subsequent transphosphorylation. Overexpression of these receptors positively correlates with transphosphorylation rates and increased tumor growth rates. MEDI4276, an anti human epidermal growth factor receptor 2 (HER2) biparatopic antibody drug conjugate, has two paratopes within each of antibody arms. One, 39S, is aiming at the HER2 site involved in receptor dimerization and the second, single chain fragment (scFv) mimicking trastuzumab...
April 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29669739/tissue-stiffening-promotes-keratinocyte-proliferation-via-activation-of-epidermal-growth-factor-signaling
#5
Fiona N Kenny, Zoe Drymoussi, Robin Delaine-Smith, Alexander P Kao, Ana Catarina Laly, Martin M Knight, Michael P Philpott, John T Connelly
Tissue biomechanics regulate a wide range of cellular functions, but the influences on epidermal homeostasis and repair remain unclear. Here, we examined the role of extracellular matrix stiffness on human keratinocyte behavior using elastomeric substrates with defined mechanical properties. Increased matrix stiffness beyond normal physiologic levels promoted keratinocyte proliferation but did not alter the ability to self-renew or terminally differentiate. Activation of epidermal growth factor (EGF) signaling mediated the proliferative response to matrix stiffness and depended on focal adhesion assembly and cytoskeletal tension...
April 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29665393/comparative-experimental-theoretical-studies-on-the-egfr-dimerization-under-the-effect-of-egf-egf-analogues-binding-highlighting-the-importance-of-egf-egfr-interactions-at-site-iii-interface
#6
Masomeh Mehrabi, Hamid Mahdiuni, Hassan Rasouli, Kamran Mansouri, Mohsen Shahlaie, Reza Khodarahmi
Epidermal growth factor receptors (EGFRs) and their cytoplasmic tyrosine kinases play significant roles in cell proliferation and signaling. All the members of the EGFR/ErbB family are primary goals for cancer therapy, particularly for tumors of breast, cervix, ovaries, kidney, esophagus, prostate and non-small-cell lung carcinoma and head and neck tumors. However, the therapeutic ability of accessible anti-ErbB agents is limited. Therefore, recognizing EGF analogues or small organic molecules with high affinity for the extracellular domain of the EGFR is a critical target on cancer research...
April 14, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29662194/an-egfr-ligand-promotes-egfr-mutant-but-not-kras-mutant-lung-cancer-in-vivo
#7
Koichi Tomoshige, Minzhe Guo, Tomoshi Tsuchiya, Takuya Fukazawa, Iris M Fink-Baldauf, William D Stuart, Yoshio Naomoto, Takeshi Nagayasu, Yutaka Maeda
EGFR ligands (e.g., EGF and TGFA) have been shown to be clinically associated with poor survival in lung cancer. Since TGFA itself initiates autochthonous tumors in liver, breast, and pancreas but not in the lung in transgenic mice in vivo, it would appear that an EGFR ligand may not initiate but rather promote lung cancer. However, it has not been proven in vivo whether lung cancer is promoted by an EGFR ligand. Using transgenic mouse models conditionally expressing EGFR L858R or Kras G12D with TGFA (an EGFR ligand) in lung epithelium, we determined that TGFA promoted the growth of EGFR L858R -lung tumors in airway regions but not that of Kras G12D -lung tumors...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29661145/therapeutic-cancer-vaccine-phase-i-clinical-tolerance-study-of-hu-rhegf-rp64k-mont-in-patients-with-newly-diagnosed-advanced-non-small-cell-lung-cancer
#8
Puyuan Xing, Hongyu Wang, Sheng Yang, Xiaohong Han, Yan Sun, Yuankai Shi
BACKGROUND: Hu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing antibody-mediated immune response, against the normal circulating self-protein antigen epidermal growth factor (EGF), which prevents its binding to and activation of the EGF receptor, inhibiting the transduction of the signals that drive cancer cell proliferation, survival and spread. This phase I study aimed to evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in NSCLC patients...
April 16, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29660312/the-egf-ras-pathway-controls-growth-in-drosophila-via-ribosomal-rna-synthesis
#9
Shrivani Sriskanthadevan-Pirahas, Joshua Lee, Savraj S Grewal
The Ras small G-protein is a conserved regulator of cell and tissue growth during animal development. Studies in Drosophila have shown how Ras can stimulate a Raf-MEK-ERK signaling pathway to control cell growth and proliferation in response to epidermal growth factor (EGF) stimulation. This work has also defined several transcription factors that can function as downstream growth effectors of EGF/Ras/ERK pathway by stimulating mRNA transcription. Here we report on stimulation of RNA polymerase I (Pol I)-mediated ribosomal RNA (rRNA) synthesis as a growth effector of Ras/ERK signalling in Drosophila...
April 13, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29660285/a-pseudo-targeted-ms-method-for-the-sensitive-analysis-of-protein-phosphorylation-in-protein-complexes
#10
Jiawen Lyu, Yan Wang, Jiawei Mao, Yating Yao, Shujuan Wang, Yong Zheng, Mingliang Ye
In this study, we presented an enrichment-free approach for the sensitive analysis of protein phosphorylation in minute amounts of samples, such as purified protein complexes. This method takes advantage of the high sensitivity of parallel reaction monitoring (PRM). Specifically, low confident phosphopeptides identified from the data dependent acquisition (DDA) dataset were used to build a pseudo-targeted list for PRM analysis to allow the identification of additional phosphopeptides with high confidence. The development of this targeted approach is very easy as the same sample and the same LC-system were used for the discovery and the targeted analysis phases...
April 16, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29659325/reactive-oxygen-species-mediates-50-hz-magnetic-field-induced-egf-receptor-clustering-via-acid-sphingomyelinase-activation
#11
Liyuan Sun, Liangjing Chen, Lina Bai, Yongpeng Xia, Xiaobo Yang, Wei Jiang, Wenjun Sun
PURPOSE: Exposure to extremely low frequency electromagnetic fields (ELF-MFs) could elicit biological effects including carcinogenesis. However, the detailed mechanisms by which these ELF-MFs interact with biological system are currently unclear. Previously, we found that a 50-Hz magnetic field (MF) exposure could induce epidermal growth factor receptor (EGFR) clustering and phosphorylation on cell membranes. In the present experiment, the possible roles of reactive oxygen species (ROS) in MF-induced EGFR clustering were investigated...
April 16, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29657585/deterioration-in-saliva-quality-in-patients-with-sj%C3%A3-gren-s-syndrome-impact-of-decrease-in-salivary-epidermal-growth-factor-on-the-severity-of-intraoral-manifestations
#12
REVIEW
Naoto Azuma, Yoshinori Katada, Hajime Sano
Background: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, especially the salivary and lacrimal glands. As a result of salivary gland dysfunction, most patients with SS have xerostomia related to a reduced salivary flow rate. In addition to the discomfort due to xerostomia, dry mouth can cause various intraoral manifestations such as refractory stomatitis, ulcer, and atrophic changes in the oral mucosa and tongue, and the patient's quality of life (QoL) is severely impaired...
2018: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29655686/physakengose-g-induces-apoptosis-via-egfr-mtor-signaling-and-inhibits-autophagic-flux-in-human-osteosarcoma-cells
#13
Hua Lin, Chao Zhang, Hao Zhang, Yuan-Zheng Xia, Chuan-Yang Zhang, Jie Luo, Lei Yang, Ling-Yi Kong
BACKGROUND: Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown. PURPOSE: To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29653231/ecsm2-an-endothelial-specific-ve-cadherin-binding-protein-has-a-tyrosine-phosphorylation-site-essential-to-cell-migration
#14
Huiyao Xiang, Jilei Ma, Pei Shen, Yueqing Wang, Hanju Huang, Chunwei Shi
Endothelial cell-specific molecule 2 (ECSM2) is a transmembrane protein located in cell-cell junction of endothelial cells (EC). ECSM2 was determined to play an important role in vascular development, EC migration, apoptosis and proliferation, however, no functional domains were determined in intracellular and extracellular region of ECSM2. In current work, functional domains of ECSM2, the relationship of ECSM2 with other endothelial specific protein such as VE-cadherin and the role of ECSM2 in neovascular diseases were determined...
April 10, 2018: Gene
https://www.readbyqxmd.com/read/29650351/overexpression-of-st5-an-activator-of-ras-has-no-effect-on-%C3%AE-cell-proliferation-in-adult-mice
#15
Kristy Ou, Jia Zhang, Yang Jiao, Zhao V Wang, Phillipp Scherer, Klaus H Kaestner
OBJECTIVE: Both Type I and Type II diabetes mellitus result from insufficient functional β-cell mass. Efforts to increase β-cell proliferation as a means to restore β-cell mass have been met with limited success. Suppression of Tumorigenicity 5 (ST5) activates Ras/Erk signaling in the presence of Epidermal Growth Factor (EGF). In the pancreatic islet, Ras/Erk signaling is required for augmented β-cell proliferation during pregnancy, suggesting that ST5 is an appealing candidate to enhance adult β-cell proliferation...
March 23, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29644924/role-of-prion-protein-egfr-multimolecular-complex-during-neuronal-differentiation-of-human-dental-pulp-derived-stem-cells
#16
Stefano Martellucci, Valeria Manganelli, Costantino Santacroce, Francesca Santilli, Luca Piccoli, Maurizio Sorice, Vincenzo Mattei
Cellular prion protein (PrPC ) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrPC in human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrPC at low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrPC with gangliosides and EGF receptor (EGF-R) during neuronal differentiation process...
April 12, 2018: Prion
https://www.readbyqxmd.com/read/29628496/ezrin-nf-%C3%AE%C2%BAb-pathway-regulates-egf-induced-epithelial-mesenchymal-transition-emt-metastasis-and-progression-of-osteosarcoma
#17
Peng Liu, Peng Yang, Zhang Zhang, Mingfa Liu, Sanbao Hu
BACKGROUND Epithelial-mesenchymal transition (EMT) is responsible for metastasis of cancers, and NF-κB can promote tumor progression. Ezrin is an important molecule participating in EMT. However, whether Ezrin mediates NF-κB in EGF-induced osteosarcoma is unknown. MATERIAL AND METHODS Ezrin phosphorylation, NF-κB activation, and EGF-induced EMT were studied in MG63 and U20S cells with NF-κB inhibition, silencing, or over-expressing Ezrin. Cell morphology, proliferation, migration, and motility were analyzed...
April 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29626349/phosphoproteome-profiling-provides-insight-into-the-mechanism-of-action-for-carvedilol-mediated-cancer-prevention
#18
Kristan H Cleveland, Steven Yeung, Kevin M Huang, Sherry Liang, Bradley T Andresen, Ying Huang
Recent studies suggest that the β-blocker drug carvedilol prevents skin carcinogenesis but the mechanism is unknown. Carvedilol is one of a few β-blockers identified as biased agonist based on an ability to promote β-arrestin-mediated processes such as ERK phosphorylation. To understand the role of phosphoproteomic signaling in carvedilol's anticancer activity, the mouse epidermal JB6 P+ cells treated with EGF, carvedilol or their combination were analyzed using the Phospho Explorer Antibody Array containing 1318 site-specific and phospho-specific antibodies of over 30 signaling pathways...
April 6, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29625025/ltbp3-pathogenic-variants-predispose-individuals-to-thoracic-aortic-aneurysms-and-dissections
#19
Dong-Chuan Guo, Ellen S Regalado, Amelie Pinard, Jiyuan Chen, Kwanghyuk Lee, Christina Rigelsky, Lior Zilberberg, Ellen M Hostetler, Micheala Aldred, Stephanie E Wallace, Siddharth K Prakash, Suzanne M Leal, Michael J Bamshad, Deborah A Nickerson, Marvin Natowicz, Daniel B Rifkin, Dianna M Milewicz
The major diseases affecting the thoracic aorta are aneurysms and acute dissections, and pathogenic variants in 11 genes are confirmed to lead to heritable thoracic aortic disease. However, many families in which multiple members have thoracic aortic disease do not have alterations in the known aortopathy genes. Genes highly expressed in the aorta were assessed for rare variants in exome sequencing data from such families, and compound rare heterozygous variants (p.Pro45Argfs∗ 25 and p.Glu750∗ ) in LTBP3 were identified in affected members of one family...
April 5, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29624182/morphology-and-dynamics-of-tumor-cell-colonies-propagating-in-epidermal-growth-factor-supplemented-media
#20
Nicolás Eduardo Muzzio, Marcos Carballido, Miguel Pasquale, Pedro Horacio González, Omar Azzaroni, Alejandro Jorge Arvia
The epidermal growth factor (EGF) plays a key role in physiological and pathological processes. This work reports on the influence of EGF concentration (<i>c</i><sub>EGF</sub>) on the modulation of individual cell phenotype and cell colony kinetics with the aim of perturbing the colony front roughness fluctuations. For this purpose, HeLa cell colonies that remain confluent along the whole expansion process with initial quasi-radial geometry and different initial cell populations, as well as colonies with initial quasi-linear geometry and large cell population, are employed...
April 6, 2018: Physical Biology
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