`Eph'ective signaling: forward, reverse and crosstalk

Abstract

The Eph receptors comprise the largest group of receptor tyrosine kinases and are found in a wide variety of cell types in developing and mature tissues. Their ligands are the ephrins, a family of membrane-bound proteins found in lipid rafts. In the past decade, Eph receptors and ephrins have been implicated in a vast array of cellular processes. Unlike other receptor tyrosine kinases, however, the Eph receptors seem to be geared towards regulating cell shape and movement rather than proliferation. Studies have uncovered intricate signaling networks that center around the ligand-receptor complex, and this may account for the broad repertoire of functions of Eph proteins. Deciphering the bi-directional pathways emanating from an Eph receptor-ephrin complex will not only help us to understand basic biological processes, but may also provide important insight into disease.

EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line

“…The Eph receptors and ephrins are divided into two subclasses, A and B, based on their homologies, structures, and binding affinities (1). Fourteen Eph receptors and eight ephrin ligands have been identified thus far in mammals (2 -4).…”

Loss of EphA2 receptor tyrosine kinase reduces Apcmin/+ tumorigenesis

“…[1][2][3][4][5][6][7][8] Eph RTKs are subdivided into class A and class B molecules based on homology and their ability to bind distinct set of membrane anchored ligands (ephrins). Class A Eph receptors bind to glycosol-phosphatidylinositol-linked class A ephrins, whereas class B Ephs bind to class B ephrins that contain a transmembrane spanning domain.…”

Bidirectional ephrin/Eph signaling in synaptic functions

“…Currently, 16 genes (EphA1-10, EphB1-6) have been identified in the vertebrate genome [66] and 14 of them are present in mammals [58]. All Eph receptors are transmembrane proteins with highly conserved extra-and intracellular domains.…”

“…Tetramers may then form higher order aggregates at higher concentrations [38], and may cluster into lipid raft microdomains on the cell membrane when interact with cytoplasmic PDZ proteins such as GRIP [4]. High-density clusters of Ephephrin complexes are believed to serve as signaling centers for the localization, concentration and activation of intracellular signaling molecules [3,4,58]. An interesting characteristic of Eph receptors and ephrin ligands is that they are capable of bidirectional signaling.…”

“…An interesting characteristic of Eph receptors and ephrin ligands is that they are capable of bidirectional signaling. Signaling pathways directly associated with Eph receptor activation are termed "forward" and those with ephrin activations, "reverse" signaling [41,58] (Fig. 1).…”