Downloaded from http://cshperspectives.cshlp.org/ on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press Eph Receptor Signaling and Ephrins Erika M. Lisabeth1, Giulia Falivelli1,2, and Elena B. Pasquale1,3 1Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 2Department of Pharmacology, University of Bologna, Bologna 40100, Italy 3Department of Pathology, University of California San Diego, La Jolla, California 92093 Correspondence:
[email protected] The Eph receptors are the largest of the RTK families. Like other RTKs, they transduce signals from the cell exterior to the interior through ligand-induced activation of their kinase domain. However, the Eph receptors also have distinctive features. Instead of binding soluble ligands, they generally mediate contact-dependent cell–cell communication by interacting with surface-associated ligands—the ephrins—on neighboring cells. Eph re- ceptor–ephrin complexes emanate bidirectional signals that affect both receptor- and ephrin-expressing cells. Intriguingly, ephrins can also attenuate signaling by Eph receptors coexpressed in the same cell. Additionally, Eph receptors can modulate cell behavior inde- pendently of ephrin binding and kinase activity. The Eph/ephrin system regulates many developmental processes and adult tissue homeostasis. Its abnormal function has been implicated in various diseases, including cancer. Thus, Eph receptors represent promising therapeutic targets. However, more research is needed to better understand the many aspects of their complex biology that remain mysterious. he Eph receptors have the prototypical RTK vent kinase activity. Furthermore, a variety of Ttopology, with a multidomain extracellular alternatively spliced forms identified for many region that includes the ephrin ligand-binding Eph receptors differ from the prototypical struc- domain, a single transmembrane segment, and a ture and have distinctive functions (Zisch and cytoplasmic region that contains the kinase do- Pasquale 1997; Pasquale 2010).