Structural studies of Eph receptor signaling

Dimitar B. Nikolov

Memorial Sloan-Kettering Cancer Center

Eph receptors represent the largest subfamily of receptor tyrosine kinases (RTKs). The Ephs and their ligands, the ephrins, are widely expressed in the developing and adult nervous system and were initially described as important regulators of axon pathfinding and neuronal cell migration. They are now also known to have roles in a diverse array of other cell-cell interactions, including those of vascular endothelial cells and specialized epithelia. Ephs are unique among other RTKs in that they fall into two subclasses with distinct ligand specificities, and in that they can also function as ligands activating bi-directional signaling. We have previously reported the crystal structure of the EphB2/ephrinB2 complex. We have now determined other structures of ephrins and Eph/ephrin complexes, which further explain the biochemical and signaling properties of the molecules. Our most recent results will be presented.