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Eph receptor

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https://www.readbyqxmd.com/read/28489586/ephrin-b2-fc-promotes-proliferation-and-migration-and-suppresses-apoptosis-in-human-umbilical-vein-endothelial-cells
#1
Li-Chun Zheng, Xiao-Qing Wang, Kun Lu, Xiao-Ling Deng, Cheng-Wei Zhang, Hong Luo, Xu-Dong Xu, Xiao-Man Chen, Lu Yan, Yi-Qing Wang, Song-Lin Shi
Tumor growth and metastasis are angiogenesis dependent. Angiogenic growth involves endothelial cell proliferation, migration, and invasion. Ephrin-B2 is a ligand for Eph receptor tyrosine kinases and is an important mediator in vascular endothelial growth factor-mediated angiogenesis. However, research offer controversial information regarding effects of ephrin-B2 on vascular endothelial cells. In this paper, proteome analyses showed that ephrin-B2/Fc significantly activates multiple signaling pathways related to cell proliferation, survival, and migration and suppresses apoptosis and cell death...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28489485/igf-1-mediates-ephrinb1-activation-in-regulating-tertiary-dentin-formation
#2
S Matsumura, A Quispe-Salcedo, C M Schiller, J S Shin, B M Locke, S Yakar, E Shimizu
Eph receptors belong to a subfamily of receptor tyrosine kinases that are activated by membrane-spanning ligands called ephrins. Previously, we demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic differentiation from dental pulp cells (DPCs) in vitro. The goal of this study was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system that govern tertiary dentin formation in vitro and in vivo. During tooth development, ephrinB1, and EphB2 were expressed in preodontoblast and odontoblasts at postnatal day 4...
May 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28472014/protection-by-the-eph-ephrin-system-against-mesenteric-ischemia-reperfusion-injury
#3
Valentina Vivo, Irene Zini, Anna Maria Cantoni, Andrea Grandi, Massimiliano Tognolini, Riccardo Castelli, Vigilio Ballabeni, Simona Bertoni, Elisabetta Barocelli
Mesenteric ischemia-reperfusion (I/R)-induced injury targets primarily endothelial and epithelial cells, leading to a cascade of inflammatory events, eventually culminating in life-threatening syndromes. Hitherto, the role of Eph, the largest family of tyrosine kinase receptors, and of their cell-bound ephrin ligands, whose interaction generates a bidirectional signaling, is still debated in I/R injury. The aim of the present work was therefore to investigate the effects produced by unidirectional activation of forward signaling (administration of chimeric protein ephrinA1-Fc), of reverse signaling (EphA2-Fc), or inhibition of both signals (monomeric EphA2 and the protein-protein interaction inhibitor UniPR1331) on the local and systemic inflammatory responses triggered by mesenteric I/R in mice...
May 2, 2017: Shock
https://www.readbyqxmd.com/read/28465671/high-expression-of-epha3-erythropoietin-producing-hepatocellular-a3-in-gastric-cancer-is-associated-with-metastasis-and-poor-survival
#4
Baongoc Nasri, Mikito Inokuchi, Toshiaki Ishikawa, Hiroyuki Uetake, Yoko Takagi, Sho Otsuki, Kazuyuki Kojima, Tatsuyuki Kawano
BACKGROUND: As the major subfamily of receptor tyrosine, erythropoietin-producing hepatocellular (Eph) receptor has been related to progression and prognosis in different types of tumors. However, the role and mechanism of EPHA3 in gastric cancer is still not well understood. METHODS: Specimen were collected from 202 patients who underwent gastric resection for gastric adenocarcinoma. The expression of EphA3 was studied using immunohistochemistry. We analyzed the clinicopathological factors and prognostic relevance of EphA3 expression in gastric cancer...
2017: BMC Clinical Pathology
https://www.readbyqxmd.com/read/28453458/reduced-ephb6-protein-in-gastric-carcinoma-and-associated-lymph-nodes-suggests-ephb6-as-a-gastric-tumor-and-metastasis-inhibitor
#5
Jiaxiu Liu, Bin Xu, Guoying Xu, Xiaolei Zhang, Xueyi Yang, Jiandong Wang
BACKGROUND: Eph receptors comprise the largest group of the receptor tyrosine kinase (RTK) family, and Eph receptors interacting with their ligand ephrins play an important role in development and tumorigenesis. EphB6, a special Eph receptor that lacks tyrosine kinase activity, was reported to be expressed in some human cancers. The clinical significance of EphB6 in gastric carcinoma has not been well investigated. METHODS: In this study, we detected expression of EphB6 protein in four gastric cancer cell lines and a set of gastric carcinoma tissue specimens by using immunohistochemistry...
April 21, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28434841/transcriptional-dependencies-in-diffuse-intrinsic-pontine-glioma
#6
Surya Nagaraja, Nicholas A Vitanza, Pamelyn J Woo, Kathryn R Taylor, Fang Liu, Lei Zhang, Meng Li, Wei Meng, Anitha Ponnuswami, Wenchao Sun, Jie Ma, Esther Hulleman, Tomek Swigut, Joanna Wysocka, Yujie Tang, Michelle Monje
Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric cancer with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone-3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using bromodomain inhibition or CDK7 blockade. Targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition, and DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28421649/decreased-expression-of-epha5-is-associated-with-fuhrman-nuclear-grade-and-pathological-tumour-stage-in-ccrcc
#7
Xiaolin Wang, Haifei Xu, Zhijun Wu, Xiao Chen, Jiandong Wang
The incidence of renal cell carcinoma is increasing all over the world. The molecular mechanisms for tumorigenesis, progression and prognosis are still unknown. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors have been reported to be expressed aberrantly in many types of human cancers and in particular EphA5 may play a role in certain human cancers. In this study, a set of clear cell renal cell carcinoma (ccRCC) tissues were subjected to immunohistochemistry. The relationship between EphA5 protein expression and clinicopathological parameters was statistically analysed...
April 19, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28370426/intramembranous-processing-by-%C3%AE-secretase-regulates-reverse-signaling-of-ephrin-b2-in-migration-of-microglia
#8
Nadja Kemmerling, Patrick Wunderlich, Sandra Theil, Bettina Linnartz-Gerlach, Nils Hersch, Bernd Hoffmann, Michael T Heneka, Bart de Strooper, Harald Neumann, Jochen Walter
The Eph-ephrin system plays pivotal roles in cell adhesion and migration. The receptor-like functions of the ephrin ligands allow the regulation of intracellular processes via reverse signaling. γ-Secretase mediated processing of ephrin-B has previously been linked to activation of Src, a kinase crucial for focal adhesion and podosome phosphorylation. Here, we analyzed the role of γ-secretase in the stimulation of reverse ephrin-B2 signaling in the migration of mouse embryonic stem cell derived microglia...
April 3, 2017: Glia
https://www.readbyqxmd.com/read/28360821/combined-ephb2-receptor-knockdown-with-radiation-decreases-cell-viability-and-invasion-in-medulloblastoma
#9
Shilpa Bhatia, Kellen Hirsch, Sanjana Bukkapatnam, Nimrah A Baig, Ayman Oweida, Anastacia Griego, Dylan Calame, Jaspreet Sharma, Andrew Donson, Nicholas Foreman, Christopher Albanese, Sujatha Venkataraman, Rajeev Vibhakar, Sana D Karam
BACKGROUND: Medulloblastoma is one of the most common types of pediatric brain tumor characterized by the subpopulation of cells that exhibit high invasive potential and radioresistant properties. In addition, dysregulated function and signaling by Eph family of receptors have been shown to impart pro-tumorigenic characteristics in this brain malignancy. In the current study, we investigated whether EphB2 knockdown in combination with radiation can alter invasiveness and decrease medulloblastoma tumor growth or viability in vitro...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28351297/epha4-promotes-cell-proliferation-and-cell-adhesion-mediated-drug-resistance-via-the-akt-pathway-in-multiple-myeloma
#10
Linlin Ding, Yaodong Shen, Jing Ni, Yiqing Ou, Yangyu Ou, Hong Liu
Eph receptor A4 (EphA4), a member of the erythropoietin-producing hepatocellular (Eph) family, has been reported to upregulate in several tumors. However, the role of EphA4 in multiple myeloma has not been clarified yet. In this study, we found that EphA4 promoted proliferation of multiple myeloma cells via the regulation of cell cycle. Besides, EphA4 was closely related to cell adhesion of multiple myeloma cells and promoted cell adhesion-mediated drug resistance by enhancing the phosphorylation levels of Akt (p-AKT) expression in multiple myeloma...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28346224/mutant-%C3%AE-2-chimaerin-signals-via-bidirectional-ephrin-pathways-in-duane-retraction-syndrome
#11
Alicia A Nugent, Jong G Park, Yan Wei, Alan P Tenney, Nicole M Gilette, Michelle M DeLisle, Wai-Man Chan, Long Cheng, Elizabeth C Engle
Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1KI/KI) that models DRS. Whole embryo imaging of Chn1KI/KI mice revealed stalled abducens nerve growth and selective trochlear and first cervical spinal nerve guidance abnormalities. Stalled abducens nerve bundles did not reach the orbit, resulting in secondary aberrant misinnervation of the lateral rectus muscle by the oculomotor nerve...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28341121/activation-of-epha1-epha-receptor-axis-attenuates-diabetic-nephropathy-in-mice
#12
Yihui Li, Hongdan Yan, Feng Wang, Shanying Huang, Yun Zhang, Zhihao Wang, Ming Zhong, Wei Zhang
The Eph family of receptor tyrosine kinases serves as key modulators of various cellular functions, including inflammation, hypertrophy and fibrosis. Recent analyses have revealed that a member of the Eph family, EphA1, plays a pivotal role in regulating insulin metabolism and kidney injury. However, the importance of EphA1 in diabetic nephropathy has not been recognized. We established a diabetic nephropathy mouse model using a high-fat diet and streptozotocin (STZ) injection. Then, the recombinant adeno-associated virus type 9 (AAV9) overexpressing EphA1 or a negative control was injected locally into the kidney...
March 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#13
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322822/asymmetry-at-cell-cell-interfaces-direct-cell-sorting-boundary-formation-and-tissue-morphogenesis
#14
REVIEW
Rosa Ventrella, Nihal Kaplan, Spiro Getsios
During development, cells of seemingly homogenous character sort themselves out into distinct compartments in order to generate cell types with specialized features that support tissue morphogenesis and function. This process is often driven by receptors at the cell membrane that probe the extracellular microenvironment for specific ligands and alter downstream signaling pathways impacting transcription, cytoskeletal organization, and cell adhesion to regulate cell sorting and subsequent boundary formation...
March 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#15
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28276447/ascl1-promotes-tangential-migration-and-confines-migratory-routes-by-induction-of-ephb2-in-the-telencephalon
#16
Yuan-Hsuan Liu, Jin-Wu Tsai, Jia-Long Chen, Wan-Shan Yang, Pei-Ching Chang, Pei-Lin Cheng, David L Turner, Yuchio Yanagawa, Tsu-Wei Wang, Jenn-Yah Yu
During development, cortical interneurons generated from the ventral telencephalon migrate tangentially into the dorsal telencephalon. Although Achaete-scute family bHLH transcription factor 1 (Ascl1) plays important roles in the developing telencephalon, whether Ascl1 regulates tangential migration remains unclear. Here, we found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Distal-less homeobox 2 (Dlx2) acted downstream of Ascl1 in promoting tangential migration along the VZ/SVZ but not IZ...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28262839/loss-of-the-eph-receptor-b6-contributes-to-colorectal-cancer-metastasis
#17
Silvia Mateo-Lozano, Sarah Bazzocco, Paulo Rodrigues, Rocco Mazzolini, Elena Andretta, Higinio Dopeso, Yolanda Fernández, Edgar Del Llano, Josipa Bilic, Lucía Suárez-López, Irati Macaya, Fernando Cartón-García, Rocio Nieto, Lizbeth M Jimenez-Flores, Priscila Guimarães de Marcondes, Yaiza Nuñez, Elsa Afonso, Karina Cacci, Javier Hernández-Losa, Stefania Landolfi, Ibane Abasolo, Santiago Ramón Y Cajal, John M Mariadason, Simo Schwartz, Toshimitsu Matsui, Diego Arango
Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role of EPHB6 in this process has not been investigated. We found here that manipulation of EPHB6 levels in colon cancer cell lines has no effect on their motility and growth on a solid substrate, soft agar or in a xenograft mouse model. We then used an EphB6 knockout mouse model to show that EphB6 inactivation does not efficiently initiate tumorigenesis in the intestinal tract. In addition, when intestinal tumors are initiated genetically or pharmacologically in EphB6(+/+) and EphB6(-/-) mice, no differences were observed in animal survival, tumor multiplicity, size or histology, and proliferation of intestinal epithelial cells or tumor cells...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255696/reconstitution-of-tcr-signaling-using-supported-lipid-bilayers
#18
Xiaolei Su, Jonathon A Ditlev, Michael K Rosen, Ronald D Vale
Biochemical reconstitution has served as an important tool for understanding the mechanisms of many cellular processes including DNA replication, transcription, translation, vesicle trafficking, and ubiquitin-mediated proteolysis. Here, we demonstrate that biochemical reconstitution can be applied to studying a complex signaling pathway involving as many as 12 proteins or protein complexes acting at the surface of model membranes. We show that a temporal sequence of events in activated T cells beginning with phosphorylation of the T cell receptor and culminating in the activation of actin polymerization can be replicated in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28214829/ephb4-regulates-self-renewal-proliferation-and-neuronal-differentiation-of-human-embryonic-neural-stem-cells-in-vitro
#19
Tingting Liu, Xianwei Zeng, Fangling Sun, Hongli Hou, Yunqian Guan, Deyu Guo, Houxi Ai, Wen Wang, Guojun Zhang
BACKGROUND/AIMS: EphB4 belongs to the largest family of Eph receptor tyrosine kinases. It contributes to a variety of pathological progresses of cancer malignancy. However, little is known about its role in neural stem cells (NSCs). This study examined whether EphB4 is required for proliferation and differentiation of human embryonic neural stem cells (hNSCs) in vitro. METHODS: We up- and down-regulated EphB4 expression in hNSCs using lentiviral over-expression and shRNA knockdown constructs and then investigated the influence of EphB4 on the properties of hNSCs...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28194092/paradoxes-of-the-ephb1-receptor-in-malignant-brain-tumors
#20
REVIEW
Wenqiang Wei, Hongju Wang, Shaoping Ji
Eph receptors are a subfamily of receptor tyrosine kinases. Eph receptor-mediated forward and ephrin ligand-mediated reverse signalings are termed bidirectional signaling. Increasing evidence shows that Eph/ephrin signaling regulates cell migration, adhesion, morphological changes, differentiation, proliferation and survival through cell-cell communication. Some recent studies have started to implicate Eph/ephrin signaling in tumorigenesis, metastasis, and angiogenesis. Previous studies have shown that EphB1 receptor and its ephrin ligands are expressed in the central nervous system...
2017: Cancer Cell International
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