Eph receptors and ephrins

Int J Biochem Cell Biol. 2003 Feb;35(2):130-4. doi: 10.1016/s1357-2725(02)00096-1.


Eph receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility. Eph signaling is crucial for the development of many tissues and organs including the nervous and cardiovascular systems. Both Ephs and ephrins are membrane-bound and their interactions at sites of cell-cell contact initiate unique bi-directional signaling cascades where information is transduced in both the receptor- and the ligand-expressing cells. Recent studies summarized in this review reveal how the signaling process is triggered upon ligand-receptor binding via the formation of a 2:2 circular heterotetramer. This fixes the orientation of the participating molecules and facilitates phosphorylation of their cytoplasmic domains which then interact with downstream signaling factors. The elucidation of the structural details of Eph-ephrin recognition and binding should yield insight into the future development of novel therapeutic agents targeting cardiovascular function, nerve regeneration, and cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Axons / metabolism
  • Cardiovascular System / growth & development
  • Cardiovascular System / metabolism
  • Ephrins / chemistry
  • Ephrins / metabolism
  • Ephrins / physiology*
  • Humans
  • Nervous System / growth & development
  • Nervous System / metabolism
  • Receptors, Eph Family / chemistry
  • Receptors, Eph Family / metabolism
  • Receptors, Eph Family / physiology*
  • Signal Transduction / physiology


  • Ephrins
  • Receptors, Eph Family