FIGURE 1.

Eph-ephrin bidirectional signaling. (A) Transmembrane Eph receptor tyrosine kinases consist of a ligand binding domain (purple semi-circle), cysteine-rich EGF-like motif (yellow rectangle), and fibronectin type III repeats (green rectangle) in the extracellular region and have a tyrosine kinase domain (blue oval), SAM domain (red triangle), and a PDZ-binding motif (green hexagon) intracellularly. The extracellular and intracellular domains are linked by a transmembrane domain. Eph receptors are divided into two classes, EphAs, and EphBs, and bind to membrane-bound ligands called ephrins. Ephrin-As are membrane-anchored via a glycosylphosphatidylinositol (GPI) moiety, and ephrin-Bs have a transmembrane domain with a short cytoplasmic extension containing a PDZ-binding motif (orange hexagon) for autophosphorylation. (B) Binding of Ephs to ephrins leads to bidirectional signaling with forward signaling in the Eph-bearing cell and reverse signaling in the ephrin-bearing cell through phosphorylation of tyrosine residues. Downstream activation of various kinases and pathways has been reviewed in detail previously (Pasquale, 2008). Illustration not drawn to scale and created with the aid of BioRender.com.