SIMILARITIES AND DIFFERENCES IN THE WAY TRANSMEMBRANE-TYPE LIGANDS INTERACT WITH THE ELK SUBCLASS OF EPH RECEPTORS

The Eph family of receptor tyrosine kinases and their cell surface bou nd ligands have been implicated in a number of developmental processes , including axon pathfinding and fasciculation, as well as patterning in the central nervous system. To better understand the complex signal ing events taking place, we have undertaken a comparative analysis of ligand-receptor interactions between a subset of ligands, those that a re tethered to the cell surface via a transmembrane domain, and a subs et of Eph receptors, the so-called Elk subclass. Based on binding char acteristics, receptor autophosphorylation, and cellular transformation assays, we find that the transmembrane-type ligands Lerk2 and Elf2 ha ve common and specific receptors within the Elk subclass of receptors. The common receptors Cek10 and Elk bind and signal in response to Ler k2 and Elf2, whereas the Myk1 receptor is specific for Elf2. Elf2, how ever, fails to signal through Cek5 in a cellular transformation assay, suggesting that Lerk2 may be the preferred Cek5 ligand in vivo. A rec ently identified third transmembrane-type ligand, Elf3, specifically, but weakly, binds Cek10 and only induces focus formation when activate d by C-terminal truncation. This suggests that the physiological Elf3 receptor may have yet to be identified. Knowledge regarding functional ligand-receptor interactions as presented in this study will be impor tant for the design and interpretation of in vivo experiments, e.g., l oss-of-function studies in transgenic mice.