• In this study, we examined whether recurrent hypoglycemia alters the capacity of the ephrinA5 ligand to activate VMH EphA5 receptors, and if so, whether these changes could contribute to pathogenesis of defective glucose counterregulation in response to a standard hypoglycemic stimulus. (diabetesjournals.org)
  • EphA5, also known as Ehk1, Bsk, Cek7, Hek7, and Rek7 (1), is a member of the Eph receptor family which binds members of the ephrin ligand family. (rndsystems.com)
  • The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. (creativebiomart.net)
  • Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. (creativebiomart.net)
  • Even though the physiological relevance of Eph/ephrin signaling has been well-proven for developmental and cancer-related processes, whether and how the ligand-mediated activation of Eph receptors triggers changes in gene expression that underlie discrete cell physiological responses is greatly unknown. (biomedcentral.com)
  • Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain. (genominfo.org)
  • Over-expression of endogenous fly Eph and RNAi-mediated knock-down of Eph and its ligand ephrin affected sleep architecture and neurophysiology. (sdbonline.org)
  • Within the central nervous system, Eph receptors and their ligands, the ephrins, play a key role in cell-to-cell communication as well as in synaptic structure and function. (diabetesjournals.org)
  • The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. (wikipedia.org)
  • Unified nomenclature for Eph family receptors and their ligands, the ephrins. (wikipedia.org)
  • Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. (creativebiomart.net)
  • Cell-cell communication is mediated by membrane receptors and their ligands, such as the Eph/ephrin system, orchestrating cell migration during development and in diverse cancer types. (biomedcentral.com)
  • Ephrin ligands and their receptors, the Eph receptor (Eph) tyrosine kinases, are cell surface molecules that mediate commu-nication between cells. (123dok.org)
  • We previously reported that EphA5 receptor-ephrinA5 interactions within the ventromedial hypothalamus (VMH) influence counterregulatory hormone responses during acute hypoglycemia in nondiabetic rats. (diabetesjournals.org)
  • These data suggest that the activation of VMH EphA5 receptors by ephrinA5 may act in concert with β-cell Eph receptor forward signaling to restore glucose homeostasis during acute hypoglycemia via alterations in glutamate/glutamine cycling ( 7 , 8 ). (diabetesjournals.org)
  • EPH receptor A5 (ephrin type-A receptor 5) is a protein that in humans is encoded by the EPHA5 gene. (wikipedia.org)
  • This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. (wikipedia.org)
  • The expression of ephrinA5, but not EphA5 receptors within the VMH, was reduced by antecedent recurrent hypoglycemia. (diabetesjournals.org)
  • Activation of VMH EphA5 receptors via targeted microinjection of ephrinA5-Fc before a hyperinsulinemic hypoglycemic clamp study caused a reduction in the glucose infusion rate in nondiabetic rats exposed to recurrent hypoglycemia. (diabetesjournals.org)
  • We have previously reported that local stimulation of VMH EphA5 receptors by microinjection of ephrinA5-Fc or ephrinA5 overexpression increased, whereas knockdown of VMH ephrinA5 reduced, counterregulatory responses to hypoglycemia. (diabetesjournals.org)
  • Ephrins and Eph receptors are especially highly expressed in the embryonic nervous system, where their signalling is important for proper axonal pathfinding and to establish topographic projections [1-3]. (123dok.org)
  • Recent studies in the hippocampus and cerebral cortex show that Eph receptors and ephrins are important in the regulation of synaptic morphology and plasticity. (123dok.org)
  • For example, in EphB1/ EphB2/EphB3-deficient mice dendritic spines (the small protru-sions bearing postsynaptic structures) have reduced density and size [3,7,8] while activation of EphB receptors by ephrins induces rapid dendritic spine formation [7,9]. (123dok.org)
  • EphA3, EphA5 and EphA4. (monossabios.com)
  • We also found EphA3, EphA4 and EphA5 to be expressed in all NSCLC cell lines analyzed yet with less appearance magnitude than EphA2 (Supplementary Body S1). (monossabios.com)
  • A trans-interaction of Eph-ephrin followed by heterotetramer formation activates the signaling cascade and transforms the kinase domain from closed to open conformation which in-turn, expose the ATP binding pocket [ 5 ]. (genominfo.org)
  • Previously, we reported ephrinA5 to trigger transcriptional changes of lncRNAs and protein-coding genes in cerebellar granule cells, a cell model for medulloblastoma. (biomedcentral.com)
  • Therefore, considering the importance of Eph-ephrin class of protein in tumorigenesis, 7,620 clinically reported missense mutations belonging to the class of variables of unknown significance were retrieved from cBioPortal and evaluated for pathogenicity. (genominfo.org)
  • EphA5 antibody detects endogenous levels of total EphA5. (affbiotech.cn)
  • Open up in another window Body 1 Endogenous appearance of Ephrin B3 or EphA2 drives proliferation and migration of NSCLC cellsA. (monossabios.com)
  • The extracellular domain facilitates binding to ephrin. (genominfo.org)
  • Eph-ephrin regulates many downstream pathways that lead to physiological events such as cell migration, proliferation, and growth. (genominfo.org)
  • RESULTS Ephrin B3 regulates NSCLC cell proliferation, migration and invasion potential We previously showed that ablation of Ephrin B3 expression in NSCLC cells inhibits EphA2 Ser897 phosphorylation, suggesting a functional connection between Ephrin B3 and EphA2 [19]. (monossabios.com)
  • Based on sequence homology, Eph and ephrin have been classified into EphA/EphrinA and EphB/EphrinB class of families [ 2 ]. (genominfo.org)
  • These data suggest that changes in ephrinA5/EphA5 interactions and synaptic plasticity within the VMH, a key glucose-sensing region in the brain, may contribute to the impairment in glucagon secretion and counterregulatory responses caused by recurrent hypoglycemia. (diabetesjournals.org)
  • Eph and ephrin are membrane-bound and thus regulate cell-cell interaction, migration, partitioning, and cell adhesion [ 3 ]. (genominfo.org)
  • Thirty-two mutations predicted to be pathogenic using SIFT, Polyphen-2, PROVEAN, SNPs&GO, PMut, iSTABLE, and PremPS in-silico tools were found located either in critical functional regions or encompassing interactions at the binding interface of Eph-ephrin. (genominfo.org)
  • The overall domain organization of EphAs and EphBs are similar, however, ephrin A is GPI anchored to the membrane, whereas ephrin B has an intracellular PDZ binding domain. (genominfo.org)
  • Following these total results, we right here demonstrate that Ephrin B3 and EphA2 are concomitantly indicated in NSCLC cells of different histology which obstructing Ephrin B3 manifestation inhibits cell proliferation, migration and invasion By immunoprecipitation and closeness ligation assay (PLA) we for the very first time display that Ephrin B3 interacts with EphA2 along with other EphAs e.g. (monossabios.com)
  • Beside its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. (creativebiomart.net)
  • Phosphoproteomic profiling of NSCLC cells where Ephrin B3 manifestation was inhibited exposed insufficient both EphA2 Ser897 and Akt Ser129 phosphorylations, indicating a signaling interaction between Ephrin EphA2 and B3 [19]. (monossabios.com)
  • To conclude, we display that obstructing Ephrin B3 manifestation inhibits NSCLC proliferation-, migration- and invasion capability which demands further research on disturbance with Ephrin B3 just as one therapeutic avenue with this tumor malignancy. (monossabios.com)
  • Furthermore, binding of Ephrin A1 CEP-18770 (Delanzomib) to EphA2 offers in prostate tumor and glioma cells been proven to stop proliferation- and invasion signaling mediated by EphA2, an impact in part due to inhibition of EphA2 Ser897 phosphorylation [15]. (monossabios.com)
  • In conclusion, we show that blocking Ephrin B3 expression inhibits NSCLC proliferation, migration and invasion capacity, which put forward studies on interference with Ephrin B3 signaling for possible therapeutic avenues in NSCLC. (monossabios.com)
  • Purified recombinant fragment of human EphA5 expressed in E. Coli. (affbiotech.cn)
  • Here, we investigate a lncRNA-mediated targeting of DNMT1 to specific gene loci by the combined power of in silico modeling of RNA/DNA interactions and wet lab approaches, in the context of the clinically relevant use case of ephrinA5-dependent regulation of cellular motility of cerebellar granule cells. (biomedcentral.com)
  • These results demonstrate a role of Eph/ephrin signalling in a range of behaviours affected in AD. (sdbonline.org)
  • Eph-ephrin as a family is ubiquitously expressed in different tissues [ 4 ]. (genominfo.org)
  • The extracellular domains of rat EphA5 share 98.5% amino acid identity with the mouse homolog and 96.5% identity with the human homolog. (rndsystems.com)
  • Utilising fly genetics, this study generated the first Drosophila model of human wild-type and P460L mutant EphA1 and tested the effects of Eph /ephrin signalling on AD-relevant behaviour and neurophysiology. (sdbonline.org)
  • The Eph/ephrin families also appear to play a role in angiogenesis (3). (rndsystems.com)
  • We previously reported that obstructing Ephrin B3 manifestation sensitizes NSCLC cells to radiotherapy (RT) [18]. (monossabios.com)
  • The Eph-ephrin complex follows an exclusive signaling pattern wherein either Eph activates Ephrin for reverse signaling, or Ephrin activates Eph for forward signaling [ 4 ]. (genominfo.org)
  • We also found that Ser897 phosphorylated EphA2 bound to Ephrin B3 is in complex with p38MAPK, phosphorylated Akt Ser129 and in some NSCLC cells also CEP-18770 (Delanzomib) Src. (monossabios.com)
  • This mediates DNA methylation-dependent silencing of Ncam1 , being abolished by ephrinA5 stimulation-triggered reduction of Snhg15 expression. (biomedcentral.com)
  • Eph over-expression led to stronger circadian morning anticipation while ephrin knock-down impaired memory. (sdbonline.org)
  • Analyses of Ephrin B3 expression in stage IA-IB NSCLC clinical specimen revealed a concomitant expression with EphA2 and Ephrin A1 with higher Ephrin B3 expression in non-squamous than in squamous tumors. (monossabios.com)
  • Immobilized Recombinant Rat EphA5 Fc Chimera at 2 µg/mL (100 µL/well) can bind Recombinant Mouse Ephrin-A2 Fc Chimera (Catalog # 603-A2 ) with a linear range of 0.16-10 ng/mL. (rndsystems.com)