Genomes and Genes
Gene Symbol: Ephb2
Description: Eph receptor B2
Alias: Cek5, Drt, ETECK, Erk, Hek5, Nuk, Prkm5, Qek5, Sek3, Tyro5, ephrin type-B receptor 2, neural kinase, nuk receptor tyrosine kinase, tyrosine-protein kinase receptor EPH-3, tyrosine-protein kinase receptor SEK-3
- Poliakov A, Cotrina M, Pasini A, Wilkinson D. Regulation of EphB2 activation and cell repulsion by feedback control of the MAPK pathway. J Cell Biol. 2008;183:933-47 pubmed publisher..We find that activation of FGFR1 in EphB2-expressing cells prevents segregation, repulsion, and collapse responses to ephrinB1 ligand...
- Himanen J, Chumley M, Lackmann M, Li C, Barton W, Jeffrey P, et al. Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci. 2004;7:501-9 pubmed..Here we show that two of the most widely studied of these molecules, EphB2 and ephrin-A5, which have never been described to interact with each other, do in fact bind one another with high ..
- Lin K, Sloniowski S, Ethell D, Ethell I. Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion. J Biol Chem. 2008;283:28969-79 pubmed publisher..Here we provide evidence of an important role for matrix metalloproteinases (MMPs) in repulsive EphB2 signaling...
- Zimmer M, Palmer A, Köhler J, Klein R. EphB-ephrinB bi-directional endocytosis terminates adhesion allowing contact mediated repulsion. Nat Cell Biol. 2003;5:869-78 pubmed..Here, we show a mechanism for the termination of adhesion and the promotion of cell repulsion after intercellular (trans) interaction between two transmembrane proteins. ..
- Henkemeyer M, Itkis O, Ngo M, Hickmott P, Ethell I. Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol. 2003;163:1313-26 pubmed..Analysis of EphB1, EphB2, and EphB3 double and triple mutant mice lacking these receptors in different combinations indicates that all ..
- Catchpole T, Henkemeyer M. EphB2 tyrosine kinase-dependent forward signaling in migration of neuronal progenitors that populate and form a distinct region of the dentate niche. J Neurosci. 2011;31:11472-83 pubmed publisher..We show here that the murine EphB2 receptor tyrosine kinase is critical for embryonic/postnatal development of a specific region of the DG known as ..
- Holmberg J, Genander M, Halford M, Annerén C, Sondell M, Chumley M, et al. EphB receptors coordinate migration and proliferation in the intestinal stem cell niche. Cell. 2006;125:1151-63 pubmed..These data establish EphB receptors as key coordinators of migration and proliferation in the intestinal stem cell niche. ..
- Chenaux G, Henkemeyer M. Forward signaling by EphB1/EphB2 interacting with ephrin-B ligands at the optic chiasm is required to form the ipsilateral projection. Eur J Neurosci. 2011;34:1620-33 pubmed publisher..mutant mice shows that EphB1 is the preferred receptor of ephrin-B2 and, to a lesser degree, ephrin-B1 in mediating axon guidance at the optic chiasm despite the coexpression of EphB2 in the same ipsilaterally projecting retinal axons.
- Hindges R, McLaughlin T, Genoud N, Henkemeyer M, O Leary D. EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping. Neuron. 2002;35:475-87 pubmed..Directed branch extension is disrupted in EphB2; EphB3-deficient mice resulting in lateral ectopic arbors...
- Contractor A, Rogers C, Maron C, Henkemeyer M, Swanson G, Heinemann S. Trans-synaptic Eph receptor-ephrin signaling in hippocampal mossy fiber LTP. Science. 2002;296:1864-9 pubmed..These findings suggest that PDZ interactions in the postsynaptic neuron and trans-synaptic interactions between postsynaptic EphB receptors and presynaptic B-ephrins are necessary for the induction of mossy fiber LTP. ..
- Adams R, Wilkinson G, Weiss C, Diella F, Gale N, Deutsch U, et al. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999;13:295-306 pubmed..Mice lacking ephrinB2 and a proportion of double mutants deficient in EphB2 and EphB3 receptor signaling die in utero before embryonic day 11.5 (E11...
- Torres R, Firestein B, Dong H, Staudinger J, Olson E, Huganir R, et al. PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron. 1998;21:1453-63 pubmed..Thus, PDZ proteins may play critical roles in localizing vertebrate receptor tyrosine kinases and/or their ligands and may be particularly important for Eph function in guidance or patterning or at the synapse. ..
- Orioli D, Henkemeyer M, Lemke G, Klein R, Pawson T. Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation. EMBO J. 1996;15:6035-49 pubmedSek4 and Nuk are members of the Eph-related family of receptor protein-tyrosine kinases. These receptors interact with a set of cell surface ligands that have recently been implicated in axon guidance and fasciculation...
- Henkemeyer M, Marengere L, McGlade J, Olivier J, Conlon R, Holmyard D, et al. Immunolocalization of the Nuk receptor tyrosine kinase suggests roles in segmental patterning of the brain and axonogenesis. Oncogene. 1994;9:1001-14 pubmedb>Neural kinase (Nuk) encodes a murine receptor-like tyrosine kinase belonging to the Eph/Elk/Eck family...
- Moeller M, Shi Y, Reichardt L, Ethell I. EphB receptors regulate dendritic spine morphogenesis through the recruitment/phosphorylation of focal adhesion kinase and RhoA activation. J Biol Chem. 2006;281:1587-98 pubmed..These data suggest that EphB receptors are upstream regulators of FAK in dendritic filopodia and that FAK-mediated RhoA activation contributes to assembly of actin filaments in dendritic spines. ..
- Dravis C, Yokoyama N, Chumley M, Cowan C, Silvany R, Shay J, et al. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol. 2004;271:272-90 pubmed..essential for proper axon pathfinding in the developing nervous system, namely ephrin-B2 and the ephrin receptors EphB2 and EphB3, also play major roles in cell adhesion events that tubularize the urethra and partition the urinary and ..
- Thakar S, Chenaux G, Henkemeyer M. Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping. Nat Commun. 2011;2:431 pubmed publisher..Although previous studies have implicated EphB2 forward signalling in mice, the intracellular component of EphB2 essential for retinocollicular mapping is unknown ..
- Bouzioukh F, Wilkinson G, Adelmann G, Frotscher M, Stein V, Klein R. Tyrosine phosphorylation sites in ephrinB2 are required for hippocampal long-term potentiation but not long-term depression. J Neurosci. 2007;27:11279-88 pubmed..At the CA3-CA1 hippocampal synapse, EphB2 and EphA4 receptors are critically involved in long-term plasticity independent of their cytoplasmic domains, ..
- Risley M, Garrod D, Henkemeyer M, McLean W. EphB2 and EphB3 forward signalling are required for palate development. Mech Dev. 2009;126:230-9 pubmed publisher..Previous work had shown that the loss of ephrinB1 protein alone or compound loss of EphB2 and EphB3 leads to cleft palate...
- Margolis S, Salogiannis J, Lipton D, Mandel Brehm C, Wills Z, Mardinly A, et al. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell. 2010;143:442-55 pubmed publisher..These findings suggest that aberrant EphB/Ephexin5 signaling during the development of synapses may contribute to the abnormal cognitive function that occurs in Angelman syndrome and, possibly, ASDs...
- Williams S, Mann F, Erskine L, Sakurai T, Wei S, Rossi D, et al. Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm. Neuron. 2003;39:919-35 pubmed..EphB1 null mice exhibit a dramatically reduced ipsilateral projection, suggesting that this receptor contributes to the formation of the ipsilateral retinal projection, most likely through its repulsive interaction with ephrin-B2. ..
- Compagni A, Logan M, Klein R, Adams R. Control of skeletal patterning by ephrinB1-EphB interactions. Dev Cell. 2003;5:217-30 pubmed..sternocostal connections were arranged asymmetrically and sternebrae were fused, defects that were phenocopied in EphB2/EphB3 receptor mutants...
- Holland S, Gale N, Gish G, Roth R, Songyang Z, Cantley L, et al. Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells. EMBO J. 1997;16:3877-88 pubmed..To investigate the biochemical mechanisms underlying such functions, we have expressed the EphB2 receptor (formerly Nuk/Cek5/Sek3) in neuronal NG108-15 cells, and have observed the tyrosine phosphorylation of ..
- Grunwald I, Korte M, Wolfer D, Wilkinson G, Unsicker K, Lipp H, et al. Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticity. Neuron. 2001;32:1027-40 pubmed..In cultured glutamatergic neurons, EphB2 receptors were recently shown to associate with NMDA receptors at synaptic sites and were suggested to play a role ..
- Bush J, Soriano P. Ephrin-B1 forward signaling regulates craniofacial morphogenesis by controlling cell proliferation across Eph-ephrin boundaries. Genes Dev. 2010;24:2068-80 pubmed publisher..phosphoproteomic and transcriptomic approaches, we show that ephrin-B1 controls proliferation in the palate by regulating the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signal transduction pathway.
- Chen Z, Sun C, Reuhl K, Bergemann A, Henkemeyer M, Zhou R. Abnormal hippocampal axon bundling in EphB receptor mutant mice. J Neurosci. 2004;24:2366-74 pubmed..adhesion of hippocampal neurons to the ligand-expressing substrates in vitro, and the loss of the receptor EphB2 abrogates the effects of ephrin-B3. In mice deficient in EphB2 and EphB3, many hippocampal axons remain in bundles...
- Attwood B, Bourgognon J, Patel S, Mucha M, Schiavon E, Skrzypiec A, et al. Neuropsin cleaves EphB2 in the amygdala to control anxiety. Nature. 2011;473:372-5 pubmed publisher..protease neuropsin is critical for stress-related plasticity in the amygdala by regulating the dynamics of the EphB2-NMDA-receptor interaction, the expression of Fkbp5 and anxiety-like behaviour...
- Tolias K, Bikoff J, Kane C, Tolias C, Hu L, Greenberg M. The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development. Proc Natl Acad Sci U S A. 2007;104:7265-70 pubmed..Here, we report that the Rac1 guanine nucleotide exchange factor Tiam1 interacts with the EphB2 receptor in a kinase-dependent manner...
- Adams R, Diella F, Hennig S, Helmbacher F, Deutsch U, Klein R. The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration. Cell. 2001;104:57-69 pubmed..Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo. ..
- Wybenga Groot L, Baskin B, Ong S, Tong J, Pawson T, Sicheri F. Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell. 2001;106:745-57 pubmed..We have solved the X-ray crystal structure to 1.9 A resolution of an autoinhibited, unphosphorylated form of EphB2 comprised of the juxtamembrane region and the kinase domain...
- Bouvier D, Corera A, Tremblay M, Riad M, Chagnon M, Murai K, et al. Pre-synaptic and post-synaptic localization of EphA4 and EphB2 in adult mouse forebrain. J Neurochem. 2008;106:682-95 pubmed publisherThe ephrin receptors EphA4 and EphB2 have been implicated in synaptogenesis and long-term potentiation in the cerebral cortex and hippocampus, where they are generally viewed as post-synaptic receptors...
- Hsieh C, Nakamura P, Luk S, MIKO I, Henkemeyer M, Cramer K. Ephrin-B reverse signaling is required for formation of strictly contralateral auditory brainstem pathways. J Neurosci. 2010;30:9840-9 pubmed publisher..We found that mice with null mutations in EphB2 and EphB3 had normal contralateral VCN-MNTB projections, yet these projections also had significant numbers of ..
- Janes P, Griesshaber B, Atapattu L, Nievergall E, Hii L, Mensinga A, et al. Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors. J Cell Biol. 2011;195:1033-45 pubmed publisher..Remarkably, coexpression of a kinase-inactive mutant EphA3 with wild-type EphB2 can cause either cross-activation or cross-inhibition, depending on relative expression...
- Bush J, Soriano P. Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism. Genes Dev. 2009;23:1586-99 pubmed publisher..reverse signaling acts autonomously in cortical axons to mediate an avoidance response to its signaling partner EphB2. These results demonstrate the importance of PDZ-dependent reverse signaling for a subset of Ephrin-B1 ..
- Henderson J, Georgiou J, Jia Z, Robertson J, Elowe S, Roder J, et al. The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron. 2001;32:1041-56 pubmed..Here, we demonstrate that EphB2 also regulates postnatal synaptic function in the mammalian CNS...
- Cowan C, Shao Y, Sahin M, Shamah S, Lin M, Greer P, et al. Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron. 2005;46:205-17 pubmed..These findings suggest an important role for Vav family GEFs as regulators of ligand-receptor endocytosis and determinants of repulsive signaling during axon guidance. ..
- Irie F, Yamaguchi Y. EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP. Nat Neurosci. 2002;5:1117-8 pubmed
- Litterst C, Georgakopoulos A, Shioi J, Ghersi E, Wisniewski T, Wang R, et al. Ligand binding and calcium influx induce distinct ectodomain/gamma-secretase-processing pathways of EphB2 receptor. J Biol Chem. 2007;282:16155-63 pubmed..Here we show that the ectodomain of EphB2 receptor is released to extracellular space following cleavage after EphB2 residue 543...
- Elowe S, Holland S, Kulkarni S, Pawson T. Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction. Mol Cell Biol. 2001;21:7429-41 pubmedActivation of the EphB2 receptor tyrosine kinase by clustered ephrin-B1 induces growth cone collapse and neurite retraction in differentiated NG108 neuronal cells...
- Chumley M, Catchpole T, Silvany R, Kernie S, Henkemeyer M. EphB receptors regulate stem/progenitor cell proliferation, migration, and polarity during hippocampal neurogenesis. J Neurosci. 2007;27:13481-90 pubmed..We show that mice lacking EphB1, and more profoundly EphB1 and EphB2, have significantly fewer neural progenitors in the hippocampus...
- Tong J, Elowe S, Nash P, Pawson T. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity. J Biol Chem. 2003;278:6111-9 pubmed..In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (..
- McClelland A, Hruska M, Coenen A, Henkemeyer M, Dalva M. Trans-synaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling. Proc Natl Acad Sci U S A. 2010;107:8830-5 pubmed publisher..Here we present evidence that a trans-synaptic interaction between EphB2 in the presynaptic compartment and ephrin-B3 in the postsynaptic compartment regulates synapse density and the ..
- Mendes S, Henkemeyer M, Liebl D. Multiple Eph receptors and B-class ephrins regulate midline crossing of corpus callosum fibers in the developing mouse forebrain. J Neurosci. 2006;26:882-92 pubmed..Our results support a significant role for ephrins and Eph receptors in CC development and may provide insight to possible mechanisms involved in axon midline crossing and human disorder. ..
- Nakamura P, Hsieh C, Cramer K. EphB signaling regulates target innervation in the developing and deafferented auditory brainstem. Dev Neurobiol. 2012;72:1243-55 pubmed publisher..We found that EphB2 and EphB3 reverse signaling are critical for the normal development of the projection from VCN to MNTB, but that ..
- Benson M, Opperman L, Westerlund J, Fernandez C, San Miguel S, Henkemeyer M, et al. Ephrin-B stimulation of calvarial bone formation. Dev Dyn. 2012;241:1901-10 pubmed publisher..EphB4 was absent in embryonic and adult skulls. However, EphB1 and EphB2, both physiological receptors for ephrin-Bs, were expressed at sites of osteogenesis, and EphB1 knockout mice ..
- Henkemeyer M, Orioli D, Henderson J, Saxton T, Roder J, Pawson T, et al. Nuk controls pathfinding of commissural axons in the mammalian central nervous system. Cell. 1996;86:35-46 pubmed..To address the biological functions of the Eph family member Nuk, two mutations in the mouse germline have been generated: a protein null allele (Nuk1) and an allele that encodes a ..
- Kayser M, McClelland A, Hughes E, Dalva M. Intracellular and trans-synaptic regulation of glutamatergic synaptogenesis by EphB receptors. J Neurosci. 2006;26:12152-64 pubmed..Here, we find that EphB2 is involved in organizing excitatory synapses through the independent activities of particular EphB2 protein ..
- Ethell I, Irie F, Kalo M, Couchman J, Pasquale E, Yamaguchi Y. EphB/syndecan-2 signaling in dendritic spine morphogenesis. Neuron. 2001;31:1001-13 pubmed..We demonstrate here that the EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this phosphorylation event is crucial for syndecan-2 ..
- Wang H, Chen Z, Anderson D. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998;93:741-53 pubmed..These results provide evidence that differences between arteries and veins are in part genetically determined and suggest that reciprocal signaling between these two types of vessels is crucial for morphogenesis of the capillary beds. ..
- North H, Zhao X, Kolk S, Clifford M, Ziskind D, Donoghue M. Promotion of proliferation in the developing cerebral cortex by EphA4 forward signaling. Development. 2009;136:2467-76 pubmed publisher..Furthermore, overexpression of ephrin B1 stimulated cell division of neighboring cells, supporting the hypothesis that ephrin B1-initiated forward signaling of EphA4 promotes cortical cell division. ..
- Xu N, Henkemeyer M. Ephrin-B3 reverse signaling through Grb4 and cytoskeletal regulators mediates axon pruning. Nat Neurosci. 2009;12:268-76 pubmed publisher..Our results reveal a previously unknown pathway that controls axon pruning and elucidate the biochemical mechanism by which ephrin-B reverse signals regulate actin dynamics to bring about the retraction of growth cones. ..
- Segura I, Essmann C, Weinges S, Acker Palmer A. Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation. Nat Neurosci. 2007;10:301-10 pubmed..We thus show an important role for ephrinB reverse signaling in spine formation and have mapped the downstream pathway involved in this process. ..
- Davy A, Bush J, Soriano P. Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome. PLoS Biol. 2006;4:e315 pubmed..Our results uncover a novel role for Eph/ephrins in regulating GJC in vivo and suggest that the pleiotropic defects seen in CFNS patients are due to improper regulation of GJC in affected tissues. ..
- Palmer A, Zimmer M, Erdmann K, Eulenburg V, Porthin A, Heumann R, et al. EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP-BL phosphatase. Mol Cell. 2002;9:725-37 pubmed..Our data suggest the presence of a switch mechanism that allows a shift from phosphotyrosine/SFK-dependent signaling to PDZ-dependent signaling. ..
- Holland S, Gale N, Mbamalu G, Yancopoulos G, Henkemeyer M, Pawson T. Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands. Nature. 1996;383:722-5 pubmed..Genetic analysis of Nuk, a murine EPH receptor that binds TM ligands, has raised the possibility that these ligands might themselves have a ..
- Raft S, Andrade L, Shao D, Akiyama H, Henkemeyer M, Wu D. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear. Dev Biol. 2014;390:51-67 pubmed publisher..Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific ..