The Eph family: a multitude of receptors that mediate cell recognition signals

Abstract

The Eph receptor tyrosine kinases are emerging as molecules that guide the migration of cells and growth cones during embryonic development. Based on their concentration in embryonic regions containing growing neuronal processes, the Eph receptors were suspected early on to have a role in regulating aspects of axon growth. The most distinctive role of the Eph receptors appears to be their ability to mediate cell-cell repulsion through the binding of a ligand on an adjacent cell surface. The repulsive interactions are presumably mediated by transient receptor activation at the boundaries of complementary regions of high ligand or receptor expression. In contrast, overlapping expression patterns may regulate cell adhesion and cytoskeletal organization with possible consequences on the overall growth and fasciculation of neuronal processes. A notable feature of Eph receptor signaling is that, upon receptor binding, responses may also be elicited in the ligand-expressing cells. A better understanding of Eph receptor function requires the elucidation of their signaling properties. Recent evidence suggests a functional interaction between the Eph receptor EphB2 and neural cell adhesion molecules of the L1 family, which have well-recognized roles in the formation of neuronal projections. Only a few cytoplasmic signaling molecules that bind to the activated Eph receptors have been identified. Several of these molecules are known to transduce signals regulating cytoskeletal organization and neurite outgrowth. It is currently unclear why there is a need for fourteen distinct Eph receptor genes, many of which appear to encode several variant forms with distinct functional properties, but it is tempting to speculate that such diversity is necessary to refine the spatial organization of embryonic structures.