Eph receptors are the largest family of receptor tyrosine kinases (RTKs). EphA receptors (EphA1-10) bind ephrinA ligands which are GPI-linked proteins and EphB receptors (EphB1-6) bind ephrinB ligands which are membrane protein with one transmembrane domain^1,2. Within each subfamily, interactions between receptor and ligand are promiscuous. In addition, Eph receptors can also bind ephrins from the other class². Forward and reverse signaling through Eph receptors is a unique characteristic to this RTK since ephrins are physically linked to the plasma membrane³.

Structurally, Eph receptors contain an extracellular ligand-binding domain, a transmembrane domain and an intracellular C-terminal domain responsible for intracellular signaling¹. Forward Eph receptor signaling involves autophosphorylation of the receptor via a tyrosine kinase domain, as well as phosphorylation of other proteins. Known effectors of the forward signaling include Src kinase and Ras/Rho GTPases². Much less is known about the reverse signaling mediated by Eph receptors. Besides from acting independently, Eph receptors can also signal in concert with other receptors. For example, Eph receptors cooperate with FGF receptor, NMDA ligand-gated ion channel and chemokine G-protein coupled receptor².

Biological activities attributed to the Eph receptor-ephrin signaling module include establishing neuronal connections, mediating neuronal plasticity and repair following neuronal injury^2,4. Eph receptors may also have a role in the immune system⁵.

Eph receptors are expressed in the developing nervous system, and in the adult brain. It is also detected in the pancreas, intestine, bone and lymphocytes. In cancer cells, Eph receptors and ephrins are overexpressed^2,6,7. They are also implicated in neurodegenerative disorders like Alzheimer’s disease¹.