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Eph receptor

Jennifer Walshe, Neil A Richardson, Najla Khaled Al Abdulsalam, Sally-Anne Stephenson, Damien G Harkin
The corneal endothelium is a monolayer of epithelial cells that lines the posterior surface of the cornea and is essential for maintenance of corneal transparency. Wound healing within the corneal endothelium typically occurs through cell spreading and migration rather than through proliferation. The mechanisms that control corneal endothelial cell migration are unclear. In this study we demonstrate that cultures of corneal endothelial cells display reduced migration in scratch wound assays, and reduced levels of E-cadherin mRNA, following suppression of ligand-activated Eph receptor signalling by treatment with lithocholic acid...
February 21, 2018: Experimental Eye Research
Jin-Shan Yang, Hui-Xing Wei, Ping-Ping Chen, Gang Wu
Multiple cellular components are involved in the complex pathological process following central nervous system (CNS) injury, including neurons, glial cells and endothelial cells. Previous studies and neurotherapeutic clinical trials have assessed the molecular mechanisms that underlie neuronal cell death following CNS injury. However, this approach has largely failed to reduce CNS damage or improve the functional recovery of patients. Erythropoietin-producing human hepatocellular (Eph) receptors and ephrin ligands have attracted considerable attention since their discovery, due to their extensive distribution and unique bidirectional signaling between astrocytes and neurons...
March 2018: Experimental and Therapeutic Medicine
Anna K Großkopf, Armin Ensser, Frank Neipel, Doris Jungnickl, Sarah Schlagowski, Ronald C Desrosiers, Alexander S Hahn
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus associated with Kaposi's sarcoma and two B-cell malignancies. The rhesus monkey rhadinovirus (RRV) is a virus of nonhuman primates that is closely related to KSHV. Eph family receptor tyrosine kinases (Ephs) are cellular receptors for the gH/gL glycoprotein complexes of both KSHV and RRV. Through sequence analysis and mutational screens, we identified conserved residues in the N-terminal domain of KSHV and RRV glycoprotein H that are critical for Eph-binding in vitro...
February 2018: PLoS Pathogens
Annie Kwon, Mihir John, Zheng Ruan, Natarajan Kannan
Ephrin (Eph) receptor tyrosine kinases have evolutionarily diverged from other tyrosine kinases to respond to specific activation and regulatory signals that requires close coupling of kinase catalytic and regulatory functions. However, the evolutionary basis for such functional coupling is not fully understood. We employed an evolutionary systems approach involving statistical mining of large sequence and structural datasets to define the hallmarks of Eph kinase evolution and functional specialization. We find that some of the most distinguishing Eph- specific residues structurally tether the flanking juxtamembrane and sterile α motif (SAM) linker regions to the kinase domain, and substitutions of these residues in EphA3 result in faster kinase activation...
February 12, 2018: Journal of Biological Chemistry
Daniela Ostrowski, Ralf Heinrich
In addition to its regulatory function in the formation of red blood cells (erythropoiesis) in vertebrates, Erythropoietin (Epo) contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system. Epo protects cells from apoptosis, reduces inflammatory responses and supports re-establishment of compromised functions by stimulating proliferation, migration and differentiation to compensate for lost or injured cells. Similar neuroprotective and regenerative functions of Epo have been described in the nervous systems of both vertebrates and invertebrates, indicating that tissue-protective Epo-like signaling has evolved prior to its erythropoietic function in the vertebrate lineage...
February 2, 2018: Journal of Clinical Medicine
Yunfeng Jin, Yi Zou, Linling Wan, Mingming Lu, Ya Liu, Guoqin Huang, Jiandong Wang, Qinghua Xi
Eph receptor‑A1 (EphA1) was the first member of the erythropoietin producing hepatocellular carcinoma (Eph) family of receptor tyrosine kinases. Although the roles of EphA1 in the tumorigenesis of various human cancers have been investigated, few studies have focused on ovarian carcinoma. The present study aimed to explore the profile of EphA1 expression in ovarian carcinomas, to analyzed the association between EphA1 expression and clinicopathologic parameters, and to investigate the roles of overexpressed EphA1 in ovarian cancer cells...
January 31, 2018: Molecular Medicine Reports
Zhi Liu, Zijian Tao, Qing Zhang, Song Wan, Fenglin Zhang, Yan Zhang, Guanyu Wu, Jiandong Wang
PURPOSE: Neoadjuvant chemotherapy is commonly used to treat patients with locally advanced breast cancer and a common option for primary operable disease. However, systemic toxicity including cardiotoxicity and inefficient delivery are significant challenges form any chemotherapeutics. The development of targeted treatments that lower the risk of toxicity has, therefore, become an active area of research in the field of novel cancer therapeutics. Mesoporous silica nanoparticles (MSNs) have attracted significant attention as efficient drug delivery carriers, due to their high surface area and tailorable mesoporous structures...
February 1, 2018: Cancer Chemotherapy and Pharmacology
Ravi Salgia, Prakash Kulkarni, Prakash S Gill
The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that include two major subclasses, EphA and EphB. They form an important cell communication system with critical and diverse roles in a variety of biological processes during embryonic development. However, dysregulation of the Eph/ephrin interactions is implicated in cancer contributing to tumour growth, metastasis, and angiogenesis. Here, we focus on EphB4 and review recent developments in elucidating its role in upper aerodigestive malignancies to include lung cancer, head and neck cancer, and mesothelioma...
January 21, 2018: Biochimica et Biophysica Acta
Chih-Ju Chang, Ming-Yuan Chang, Szu-Yi Chou, Chi-Chen Huang, Jian-Ying Chuang, Tsung-I Hsu, Hsing-Fang Chang, Yi-Hsin Wu, Chung-Che Wu, Daniel Morales, Artur Kania, Tzu-Jen Kao
The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb...
January 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lian Hui, Jingru Zhang, Xiaoxu Ding, Xing Guo, Xuejun Jang
The present study aimed to identify potentially critical differentially methylated genes associated with the progression of nasopharyngeal carcinoma (NPC). Methylation profiling data of GSE62336 deposited in the Gene Expression Omnibus database were used to identify differentially methylated regions (DMRs) and differentially methylated CpG islands (DMIs). Concurrently, differentially expressed genes (DEGs) were identified using a meta-analysis of three gene expression datasets (GSE53819, GSE13597 and GSE12452)...
December 2017: Oncology Letters
Yujia Wang, Wei Shi, Alexandre Blanchette, Junzheng Peng, Shijie Qi, Hongyu Luo, Jonathan Ledoux, Jiangping Wu
Erythropoietin-producing human hepatocellular receptor (EPH) B6 (EPHB6) is a member of the receptor tyrosine kinase family. We previously demonstrated that EPHB6 knockout reduces catecholamine secretion in male but not female mice, and castration reverses this phenotype. We showed here that male EPHB6 knockout adrenal gland chromaffin cells presented reduced acetylcholine-triggered Ca2+ influx. Such reduction depended on the non-genomic effect of testosterone. Increased large conductance calcium-activated potassium channel current densities were recorded in adrenal gland chromaffin cells from male EPHB6 knockout mice but not from castrated knockout or female knockout mice...
January 16, 2018: Scientific Reports
Abdelkader Daoud, Udhayakumar Gopal, Jasmine Kaur, Jennifer S Isaacs
The Eph receptor tyrosine kinase family member EphA2 plays a pivotal role in modulating cytoskeletal dynamics to control cancer cell motility and invasion. EphA2 is frequently upregulated in diverse solid tumors and has emerged as a viable druggable target. We previously reported that extracellular Hsp90 (eHsp90), a known pro-motility and invasive factor, collaborates with EphA2 to regulate tumor invasion in the absence of its cognate ephrin ligand. Here, we aimed to further define the molecular and functional relationship between EphA2 and eHsp90...
December 5, 2017: Oncotarget
Su Hwan Lee, Ju Hye Shin, Joo Han Song, Ah Young Leem, Moo Suk Park, Young Sam Kim, Joon Chang, Kyung Soo Chung
The Eph/ephrin receptor ligand system is known to play a role in inflammation induced by infection, injury, and inflammatory diseases. The present study aimed to evaluate plasma EphA2 receptor levels in critically ill patients with sepsis. This study was a prospective cohort study evaluating samples and clinical data from the medical intensive care unit (MICU) of a 2000-bed university tertiary referral hospital in South Korea. Positive correlations of the plasma EphA2 receptor level with the acute physiology and chronic health evaluation (APACHE) II score and the sequential organ failure assessment (SOFA) score were observed...
December 14, 2017: Scientific Reports
Shao-Nan Yu, Gui-Feng Liu, Long-Yun Li, Guo-Qing Zhao, Lin Liu, Xue-Feng Li
The study aims to investigate the analgesic effects of microRNA-129-5p (miR-129-5p) on bone cancer pain (BCP) by targeting Eph receptor B1 (EphB1) through the EphB1/EphrinB2 signaling pathway. BCP mice models were established, and C3H/HeJ female mice were classified into the normal, blank, negative control (NC), miR-129-5p mimics, miR-129-5p inhibitors, EphB1 knockout (KO), and miR-129-5p inhibitors + EphB1 KO groups. RT-qPCR and western blotting were used to evaluate miR-129-5p expression, and mRNA and protein expressions of EphB1, p-EphB1, EphrinB2 and p-EphrinB2...
December 13, 2017: Journal of Cellular Biochemistry
Jian Sun, Xiaolei Wang, Yu Shi, Jiejing Li, Chaocui Li, Zhaoying Shi, Yonglong Chen, Bingyu Mao
Eph/ephrin molecules are widely expressed during embryonic development, and function in a variety of developmental processes. Here we studied the roles of the Eph receptor EphA7 and its soluble form in Xenopus pronephros development. EphA7 is specifically expressed in pronephric tubules at tadpole stages and knockdown of EphA7 by a translation blocking morpholino led to defects in tubule cell differentiation and morphogenesis. A soluble form of EphA7 (sEphA7) was also identified. Interestingly, the membrane level of claudin6 (CLDN6), a tetraspan transmembrane tight junction protein, was dramatically reduced in the translation blocking morpholino injected embryos, but not when a splicing morpholino was used, which blocks only the full length EphA7...
January 8, 2018: Biochemical and Biophysical Research Communications
Minjoo Kim, Hye Jin Yoo, Minkyung Kim, Jiyoo Kim, Seung Han Baek, Min Song, Jong Ho Lee
BACKGROUND: Erythropoietin-producing human hepatocellular (Eph) receptors might contribute to the development of atherosclerosis. A genome-wide association study indicated that the Eph receptor A6 gene (EPHA6) associated with at least 1 blood pressure (BP) phenotype. The objective of the present study was to determine whether EPHA6 is a novel candidate gene for hypertension in a Korean population. METHODS: A total 2146 study participants with normotension and hypertension were included...
December 6, 2017: Lipids in Health and Disease
Phylicia A Aaron, Mantana Jamklang, John P Uhrig, Angie Gelli
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningitis most commonly in populations with impaired immunity. Here, we resolved the transcriptome of the human brain endothelium challenged with C. neoformans to establish whether C. neoformans invades the CNS by co-opting particular signalling pathways as a means to promote its own entry. Among the 5 major pathways targeted by C. neoformans, the EPH-EphrinA1 (EphA2) tyrosine kinase receptor-signalling pathway was examined further...
March 2018: Cellular Microbiology
Samuel Ojosnegros, Francesco Cutrale, Daniel Rodríguez, Jason J Otterstrom, Chi Li Chiu, Verónica Hortigüela, Carolina Tarantino, Anna Seriola, Stephen Mieruszynski, Elena Martínez, Melike Lakadamyali, Angel Raya, Scott E Fraser
Eph receptor signaling plays key roles in vertebrate tissue boundary formation, axonal pathfinding, and stem cell regeneration by steering cells to positions defined by its ligand ephrin. Some of the key events in Eph-ephrin signaling are understood: ephrin binding triggers the clustering of the Eph receptor, fostering transphosphorylation and signal transduction into the cell. However, a quantitative and mechanistic understanding of how the signal is processed by the recipient cell into precise and proportional responses is largely lacking...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
Sara Charmsaz, Andrew W Boyd
No abstract text is available yet for this article.
October 10, 2017: Oncotarget
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