PMID: 15107857

 

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Title : Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling

Abstract :
  1. The interactions between Eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding
  2. The EphA receptors are generally thought to become activated by ephrin-A ligands, whereas the EphB receptors interact with ephrin-B ligands
  3. 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
  4. Exposure of EphB2-expressing cells to ephrin-A5 leads to receptor clustering, autophosphorylation and initiation of downstream signaling
  5. Ephrin-A5 induces EphB2-mediated growth cone collapse and neurite retraction in a model system
  6. 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
  7. 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