Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling
JP Himanen, MJ Chumley, M Lackmann, C Li… - Nature …, 2004 - nature.com
JP Himanen, MJ Chumley, M Lackmann, C Li, WA Barton, PD Jeffrey, C Vearing, D Geleick…
Nature neuroscience, 2004•nature.comThe 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 …
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 …
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.
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