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https://www.readbyqxmd.com/read/29158322/optogenetic-activation-of-ephb2-receptor-in-dendrites-induced-actin-polymerization-by-activating-arg-kinase
#1
Clifford Locke, Kazuya Machida, Yi Wu, Ji Yu
Erythropoietin-producing hepatocellular (Eph) receptors regulate a wide array of developmental processes by responding to cell-cell contacts. EphB2 is well-expressed in brain and known to be important for dendritic spine development, as well as for the maintenance of the synapses, although the mechanisms of these functions have not been fully understood. Here we studied EphB2's functions in hippocampal neurons with an optogenetic approach, which allows us to specify spatial regions of signal activation and monitor in real-time the consequences of signal activation...
November 20, 2017: Biology Open
https://www.readbyqxmd.com/read/29137214/eph-receptors-as-oncotargets
#2
EDITORIAL
Sara Charmsaz, Andrew W Boyd
No abstract text is available yet for this article.
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129483/pharmacological-evaluation-of-new-bioavailable-small-molecules-targeting-eph-ephrin-interaction
#3
Carmine Giorgio, Matteo Incerti, Miriam Corrado, Marco Rusnati, Paola Chiodelli, Simonetta Russo, Donatella Callegari, Francesca Ferlenghi, Vigilio Ballabeni, Elisabetta Barocelli, Alessio Lodola, Massimiliano Tognolini
Eph/ephrin system is an emerging target for cancer therapy but the lack of potent, stable and orally bioavailable compounds is impairing the development of the field. Since 2009 our research group has been devoted to the discovery and development of small molecules targeting Eph/ephrin system and our research culminated with the synthesis of UniPR129, a potent but problematic Eph/ephrin antagonist. Herein, we describe the in vitro pharmacological properties of two derivatives (UniPR139 and UniPR502) stemmed from structure of UniPR129...
November 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29128632/genome-wide-mapping-of-estrogen-receptor-%C3%AE-binding-sites-by-chip-seq-to-identify-genes-related-to-sexual-maturity-in-hens
#4
Miao Guo, Yi Li, Yuxia Chen, Xiaoli Guo, Zhenjie Yuan, Yunliang Jiang
In ovarian follicle development, estrogen acts as a regulatory molecule to mediate proliferation and differentiation of follicular cells. ERα (estrogen receptor α) exerts regulatory function classically by binding directly to the estrogen response element, recruiting co-factors and activating or repressing transcription in response to E2. In this study, we used ChIP-seq to map ERα-binding sites in ovaries of Hy-line Brown commercial hens at 45d, 90d and 160d. In total, 24,886, 21,680 and 23,348 binding sites were identified in the ovaries of hens at 45d, 90d and 160d, which are linked to 86, 83 and 74 genes, respectively...
November 8, 2017: Gene
https://www.readbyqxmd.com/read/29113248/gene-expression-profile-comparison-between-colorectal-cancer-and-adjacent-normal-tissues
#5
Qian Yang, Maohui Feng, Xiang Ma, Huachi Li, Wei Xie
The present study aimed to compare gene expression profiles between colorectal cancer and adjacent normal tissues, and to perform a preliminarily analysis of the key genes and underlying molecular mechanisms implicated in colorectal cancer development. Gene expression microarray chips were used to screen genes that were differently expressed between colorectal cancer and adjacent normal tissues. Approximately 1,183 genes were differentially expressed in cancer tissues compared with adjacent normal tissues (P≤0...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29059157/ephrinb1-promotes-cancer-cell-migration-and-invasion-through-the-interaction-with-rhogdi1
#6
H J Cho, Y-S Hwang, J Yoon, M Lee, H G Lee, I O Daar
Eph receptors and their corresponding ephrin ligands have been associated with regulating cell-cell adhesion and motility, and thus have a critical role in various biological processes including tissue morphogenesis and homeostasis, as well as pathogenesis of several diseases. Aberrant regulation of Eph/ephrin signaling pathways is implicated in tumor progression of various human cancers. Here, we show that a Rho family GTPase regulator, Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1), can interact with ephrinB1, and this interaction is enhanced upon binding the extracellular domain of the cognate EphB2 receptor...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29039721/a-recurrent-splice-site-mutation-in-epha2-causing-congenital-posterior-nuclear-cataract
#7
Vanita Berry, Nikolas Pontikos, Monica Albarca-Aguilera, Vincent Plagnol, Andreas Massouras, DeQuincy Prescott, Anthony T Moore, Gavin Arno, Michael E Cheetham, Michel Michaelides
Intoduction: Inherited cataract, opacification of the lens, is the most common worldwide cause of blindness in children. We aimed to identify the genetic cause of autosomal dominant (AD) posterior nuclear cataract in a four generation British family. METHODS: Whole genome sequence (WGS) was performed on two affected and one unaffected individual of the family and further validated by direct sequencing. Haplotype analysis was performed via genotying. RESULTS: A splice-site mutation c...
October 17, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28993206/targeting-receptor-tyrosine-kinase-ephb4-in-cancer-therapy
#8
REVIEW
Yinnan Chen, Hongmei Zhang, Yanmin Zhang
Eph receptors and their Eph receptor-interacting (ephrin) ligands together form an important cell communication system with diverse roles. Experimental evidence demonstrated Eph receptor bidirectional signaling with both tumor-suppressing and tumor-promoting activities in cancer cells. The tyrosine kinase EphB4, a member of the Eph receptor family, has been associated with tumor angiogenesis, growth and metastasis, thus making it a valuable and attractive target for drug design for therapeutic applications...
October 6, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28985758/pharmacological-targeting-of-the-ephrin-receptor-kinase-signalling-by-glpg1790-in-vitro-and-in-vivo-reverts-oncophenotype-induces-myogenic-differentiation-and-radiosensitizes-embryonal-rhabdomyosarcoma-cells
#9
Francesca Megiorni, Giovanni Luca Gravina, Simona Camero, Simona Ceccarelli, Andrea Del Fattore, Vincenzo Desiderio, Federica Papaccio, Heather P McDowell, Rajeev Shukla, Antonio Pizzuti, Filip Beirinckx, Philippe Pujuguet, Laurent Saniere, Ellen Van der Aar, Roberto Maggio, Francesca De Felice, Cinzia Marchese, Carlo Dominici, Vincenzo Tombolini, Claudio Festuccia, Francesco Marampon
BACKGROUND: EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines. METHODS: EPH-A2 and Ephrin-A1 mRNA expression was quantified by real-time PCR in 14 ERMS tumour samples and in normal skeletal muscle (NSM). GLPG1790 effects were tested in RD and TE671 cell lines, two in vitro models of ERMS, by performing flow cytometry analysis, Western blotting and immunofluorescence experiments...
October 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28972287/eps15r-and-clathrin-regulate-ephb2-mediated-cell-repulsion
#10
Emma Evergren, Neville Cobbe, Harvey T McMahon
Expression of Eph receptors and their ligands, the ephrins, have important functions in boundary formation and morphogenesis in both adult and embryonic tissue. The EphB receptors and ephrinB ligands are transmembrane proteins that are expressed in different cells and their interaction drives cell repulsion. For cell repulsion to occur, trans-endocytosis of the inter-cellular receptor-ligand EphB-ephrinB complex is required. The molecular mechanism underlying trans-endocytosis is poorly defined. Here we show that the process is clathrin- and Eps15R-mediated using Co115 colorectal cell lines stably expressing EphB2 and ephrinB1...
October 3, 2017: Traffic
https://www.readbyqxmd.com/read/28947862/a-review-on-eph-ephrin-angiogenesis-and-lymphangiogenesis-in-gastric-colorectal-and-pancreatic-cancers
#11
Julia Rudno-Rudzińska, Wojciech Kielan, Ewelina Frejlich, Krzysztof Kotulski, Wojciech Hap, Krzysztof Kurnol, Przemysław Dzierżek, Marcin Zawadzki, Agnieszka Hałoń
Erythroprotein-producing human hepatocellular carcinoma receptors (Eph receptors) compose a subfamily of transmembrane protein-tyrosine kinases receptors that takes part in numerous physiological and pathological processes. Eph family receptor-interacting proteins (Ephrins) are ligands for those receptors. Eph/ephrin system is responsible for the cytoskeleton activity, cell adhesion, intercellular connection, cellular shape as well as cell motility. It affects neuron development and functioning, bone and glucose homeostasis, immune system and correct function of enterocytes...
August 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/28931592/ubiquitin-ligase-spsb4-diminishes-cell-repulsive-responses-mediated-by-ephb2
#12
Fumihiko Okumura, Akiko Joo-Okumura, Keisuke Obara, Alexander Petersen, Akihiko Nishikimi, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura
Eph receptor tyrosine kinases and their ephrin ligands are overexpressed in various human cancers, including colorectal malignancies, suggesting important roles in many aspects of cancer development and progression as well as in cellular repulsive responses. The ectodomain of EphB2 receptor is cleaved by metalloproteinases (MMPs) MMP-2/MMP-9 and released into the extracellular space after stimulation by its ligand. The remaining membrane-associated fragment is further cleaved by the presenilin-dependent γ-secretase and releases an intracellular peptide that has tyrosine kinase activity...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28910333/reduced-proliferation-of-endothelial-colony-forming-cells-in-unprovoked-venous-thromboembolic-disease-as-a-consequence-of-endothelial-dysfunction
#13
Rubicel Hernandez-Lopez, Antonieta Chavez-Gonzalez, Patricia Torres-Barrera, Dafne Moreno-Lorenzana, Norma Lopez-DiazGuerrero, David Santiago-German, Irma Isordia-Salas, David Smadja, Mervin C Yoder, Abraham Majluf-Cruz, J Antonio Alvarado-Moreno
BACKGROUND: Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). METHODS AND RESULTS: Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs...
2017: PloS One
https://www.readbyqxmd.com/read/28851287/epha-receptors-and-ephrin-a-ligands-are-upregulated-by-monocytic-differentiation-maturation-and-promote-cell-adhesion-and-protrusion-formation-in-hl60-monocytes
#14
Midori Mukai, Norihiko Suruga, Noritaka Saeki, Kazushige Ogawa
BACKGROUND: Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins and integrin ligands in two monocyte/macrophage cell lines. Although mature mononuclear leukocytes express several members of the EphA/ephrin-A subclass, their expression has not been examined in monocytes undergoing during differentiation and maturation...
August 29, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28792499/revisiting-chemoaffinity-theory-chemotactic-implementation-of-topographic-axonal-projection
#15
Honda Naoki
Neural circuits are wired by chemotactic migration of growth cones guided by extracellular guidance cue gradients. How growth cone chemotaxis builds the macroscopic structure of the neural circuit is a fundamental question in neuroscience. I addressed this issue in the case of the ordered axonal projections called topographic maps in the retinotectal system. In the retina and tectum, the erythropoietin-producing hepatocellular (Eph) receptors and their ligands, the ephrins, are expressed in gradients. According to Sperry's chemoaffinity theory, gradients in both the source and target areas enable projecting axons to recognize their proper terminals, but how axons chemotactically decode their destinations is largely unknown...
August 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28777434/bifunctional-role-of-ephrin-a1-eph-system-in-stimulating-cell-proliferation-and-protecting-cells-from-cell-death-through-the-attenuation-of-er-stress-and-inflammatory-responses-in-bovine-mammary-epithelial-cells
#16
Minkyung Kang, Wooyoung Jeong, Hyocheol Bae, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Structural and functional development of the mammary gland is constant in the mammary gland life cycle. Eph receptors and their ligands, ephrins, control events through cell-to-cell interactions during embryonic development and adult tissue homeostasis; however, little information on participation of ephrin A1, a representative ligand of the Eph receptor, in the development and function of normal mammary glands is known. In this study, we demonstrated functional effects of the ephrin A1-Eph system and mechanisms of its action on bovine mammary epithelial (MAC-T) cells...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28768156/the-syk-kinases-orchestrate-cerebellar-granule-cell-tangential-migration
#17
Aurélien Benon, Choua Ya, Laurent Martin, Chantal Watrin, Naura Chounlamountri, Iness Jaaoini, Jérôme Honnorat, Véronique Pellier-Monnin, Nelly Noraz
The tyrosine kinases of the Syk family are essential components of the well-characterized immunoreceptor ITAM-based signaling pathway. However, ITAM-based signaling typically does not function in isolation. Instead, it is enmeshed in the molecular network controlling cellular adhesion and chemotaxis. Consistent with the increasing number of data involving ITAM-bearing molecules in neuronal functions, we previously depicted a role for Syk kinases in the establishment of neuronal connectivity. In the developing cerebellum, we found that Syk is essentially expressed in the granule cells (GC) and more importantly, phosphorylated on tyrosine residues representative of an active form of the kinase in tangentially migrating GC...
July 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/28751189/targeted-therapies-in-hematological-malignancies-using-therapeutic-monoclonal-antibodies-against-eph-family-receptors
#18
REVIEW
Sara Charmsaz, Andrew M Scott, Andrew W Boyd
The use of monoclonal antibodies (mAbs) and molecules derived from them has achieved considerable attention and success in recent years, establishing this mode of therapy as an important therapeutic strategy in many cancers, in particular hematological tumors. mAbs recognize cell surface antigens expressed on target cells and mediate their function through various mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, or immune system modulation. The efficacy of mAb therapy can be improved when they are conjugated to a highly potent payloads, including cytotoxic drugs and radiolabeled isotopes...
October 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28747680/glycoengineering-of-epha4-fc-leads-to-a-unique-long-acting-and-broad-spectrum-eph-receptor-therapeutic-antagonist
#19
Cassandra L Pegg, Leanne T Cooper, Jing Zhao, Michael Gerometta, Fiona M Smith, Michael Yeh, Perry F Bartlett, Jeffrey J Gorman, Andrew W Boyd
Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins. We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist. However, a very short in vivo half-life effectively limited its therapeutic development...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747399/cell-segregation-and-border-sharpening-by-eph-receptor-ephrin-mediated-heterotypic-repulsion
#20
Harriet B Taylor, Anaïs Khuong, Zhonglin Wu, Qiling Xu, Rosalind Morley, Lauren Gregory, Alexei Poliakov, William R Taylor, David G Wilkinson
Eph receptor and ephrin signalling has a major role in cell segregation and border formation, and may act through regulation of cell adhesion, repulsion or tension. To elucidate roles of cell repulsion and adhesion, we combined experiments in cell culture assays with quantitations of cell behaviour which are used in computer simulations. Cells expressing EphB2, or kinase-inactive EphB2 (kiEphB2), segregate and form a sharp border with ephrinB1-expressing cells, and this is disrupted by knockdown of N-cadherin...
July 2017: Journal of the Royal Society, Interface
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