Biology Reference
In-Depth Information
Introduction
Eph receptor tyrosine kinases and their surface-bound ligands, the ephrins,
play a key role in the patterning of many tissues during embryonic
development (Kullander and Klein, 2002; Wilkinson, 2000). Their impor-
tance in vascular development, tissue-border formation, cell migration and
axon guidance is well described. In contrast with most receptor tyrosine
kinases, Eph receptor activation occurs through direct cell-cell contact since
the ephrins are cell surface molecules. The cellular response to Eph receptor/
ephrin interaction can be repulsion, for example between neighbouring
epithelial or endothelial cells or as the neuronal growth cone navigates its
way towards its target. In other circumstances the Eph receptor/ephrin
interaction can lead to an attractive or adhesive response (Holmberg and
Frisen, 2002). It has recently been shown that upon Eph receptor binding, a
response is induced in the ephrin-expressing cell (Kullander and Klein, 2002;
Wilkinson, 2000). This capacity for bi-directional signalling allows both
receptor- and ligand-expressing cells to be influenced by the mutual contact.
Although the signalling pathways downstream of Eph receptors and ephrins
that regulate cell repulsion/attraction responses are unclear, it appears that
these pathways converge to regulate the actin cytoskeleton and cell
adhesion.
Eph receptor and ephrin families
The Eph receptors and ephrins are numerous; currently 14 Eph receptors and
eight ephrins have been identified. Eph receptors comprise the largest receptor
tyrosine kinase family, accounting for one-third of all tyrosine kinase
receptors. The ligands and the receptors each exist in one of two classes, A
or B, based on structural similarity within the class, and the a
nity of their
binding to a cognate partner (Gale et al., 1996). The ephrin-A ligands are
attached to the outer leaflet of the plasma membrane via a glycosylphos-
phatidylinositol (GPI) anchor, whereas proteins of the ephrin-B class have a
transmembrane region and a short cytoplasmic tail. Generally A-class
receptors bind A-class ligands and B-class receptors bind B-class ligands.
The exception is EphA4, which can bind both A-class and some B-class
ligands.
Eph receptor/ephrin regulation of axon guidance
The most studied situation in which Eph receptor/ephrin function plays a
critical role is axon path-finding. During embryonic development many
