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- Title
Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling.
- Authors
Himanen, Juha-Pekka; Chumley, Michael J; Lackmann, Martin; Li, Chen; Barton, William A; Jeffrey, Phillip D; Vearing, Christopher; Geleick, Detlef; Feldheim, David A; Boyd, Andrew W; Henkemeyer, Mark; Nikolov, Dimitar B
- 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.
- Publication
Nature neuroscience, 2004, Vol 7, Issue 5, p501
- ISSN
1097-6256
- Publication type
Journal Article
- DOI
10.1038/nn1237