Repelling class discrimination: Ephrin-A5 binds to and activates EphB2 receptor signaling Journal Article
| Authors: | Himanen, J. P.; Chumley, M. J.; Lackmann, M.; Li, C.; Barton, W. A.; Jeffrey, P. D.; Vearing, C.; Geleick, D.; Feldheim, D. A.; Boyd, A. W.; Henkemeyer, M.; Nikolov, D. B. |
| Article Title: | Repelling class discrimination: Ephrin-A5 binds to and activates EphB2 receptor signaling |
| Abstract: | The interactions between Eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding. The EphA receptors are generally thought to become activated by ephrin-A ligands, whereas the EphB receptors interact with ephrin-B ligands. 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 affinity. Exposure of EphB2-expressing cells to ephrin-A5 leads to receptor clustering, autophosphorylation and initiation of downstream signaling. Ephrin-A5 induces EphB2-mediated growth cone collapse and neurite retraction in a model system. We further show, using X-ray crystallography, that the ephrin-A5-EphB2 complex is a heterodimer and is architecturally distinct from the tetrameric EphB2-ephrin-B2 structure. The structural data reveal the molecular basis for EphB2-ephrin-A5 signaling and provide a framework for understanding the complexities of functional interactions and crosstalk between A- and B-subclass Eph receptors and ephrins. |
| Keywords: | signal transduction; controlled study; protein expression; human cell; nonhuman; binding affinity; protein function; protein localization; animal cell; mouse; animals; mice; infection; embryo; protein protein interaction; cell line; spectrometry, fluorescence; protein binding; transfection; protein tyrosine kinase; autophosphorylation; phosphorylation; time factors; luminescent proteins; alkaline phosphatase; fluorescent antibody technique; neuroblastoma; green fluorescent proteins; animals, newborn; protein structure; structure analysis; x ray crystallography; surface plasmon resonance; ephrin receptor b2; receptor, ephb2; model; electrophoresis; chromatography, gel; cricetinae; cricetulus; crystallography; video recording; ephrin b2; ephrin-a5; ephrin a5; ephrin-b2; receptor, epha3; chromatography, ion exchange; neurite; neurites; sindbis virus; humans; human; priority journal; article |
| Journal Title: | Nature Neuroscience |
| Volume: | 7 |
| Issue: | 5 |
| ISSN: | 1097-6256 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2004-05-01 |
| Start Page: | 501 |
| End Page: | 509 |
| Language: | English |
| DOI: | 10.1038/nn1237 |
| PROVIDER: | scopus |
| PUBMED: | 15107857 |
| DOI/URL: | |
| Notes: | Nat. Neurosci. -- Cited By (since 1996):250 -- Export Date: 16 June 2014 -- CODEN: NANEF -- Source: Scopus |
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