EphA receptor signaling—Complexity and emerging themes

The impact of Eph and ephrin signaling on cell behavior is complex and highly context dependent. Forward signaling initiated by Eph receptor activation and reverse signaling initiated by ephrin activation often mediate opposite effects. The apparent ligand-independent functions of Eph receptors recognized recently add another layer of complexity. This review will attempt to sort out the information generated recently on signaling by the A subfamily of Eph receptors and ephrin ligands. We will focus on EphA/ephrin-A signaling in the context of several physiological and disease processes, where new progresses have been made lately and unifying themes are emerging amid previous confusions. For more comprehensive survey of literature on Eph/ephrin signaling pathways and networks, readers are referred to outstanding reviews both in this volume and in other recent publications.

► EphA signaling is cell-context dependent.
► EphA receptors have both ligand-dependent and -independent signaling mechanisms.
► EphA signaling is intimately intertwined with other cellular signaling networks.
► Signaling by EphA receptor and ephrin-A ligands often mediate opposing functions.