Cell-cell signaling via Eph receptors and ephrins

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 11/2007; 19(5):534-42. DOI: 10.1016/
Source: PubMed


Eph receptors are the largest subfamily of receptor tyrosine kinases regulating cell shape, movements, and attachment. The interactions of the Ephs with their ephrin ligands are restricted to the sites of cell-cell contact since both molecules are membrane attached. This review summarizes recent advances in our understanding of the molecular mechanisms underlining the diverse functions of the molecules during development and in the adult organism. The unique properties of this signaling system that are of highest interest and have been the focus of intense investigations are as follows: (i) the signal is simultaneously transduced in both ligand-expressing cells and receptor-expressing cells, (ii) signaling via the same molecules can generate opposing cellular reactions depending on the context, and (iii) the Ephs and the ephrins are divided into two subclasses with promiscuous intrasubclass interactions, but rarely observed intersubclass interactions.

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    • "Eph (Erythropoietin Producing Hepatoma) receptors comprise the largest family of tyrosine kinases and are divided into two classes of EphAs and EphBs based on their sequence homology. Receptor activation occurs via their membrane bound ligands ephrinAs and ephrinBs, respectively [2]. "
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    • "Eph receptor–ephrin ligand interactions depend upon direct cell–cell interactions and are unique in that they trigger bidirectional signalling within the receptor and ligand-expressing cell. Upon binding their ephrin ligands, Eph receptors cluster together and heterodimerize, leading to receptor autophosphorylation on several intracellular tyrosine residues (Himanen et al., 2007). Ephrin-B ligands can also be phosphorylated on their intracellular domains. "
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    • "In this respect, extracellular receptor predimerization could also play an important role in generating the ultra high affinities observed in a physiological setting. Interestingly, a number of other RTKs, such as the IGF1 (Lawrence et al., 2007), EGFR (Chung et al., 2010; Mi et al., 2011) and Eph (Himanen et al., 2007) receptors do form oligomers in the absence of cytokine ligand. Nonetheless, hCSF-1R D1-D5 would have to undergo dramatic domain rearrangements to bind hCSF-1. "
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