THE EEK RECEPTOR, A MEMBER OF THE EPH FAMILY OF TYROSINE PROTEIN-KINASES, CAN BE ACTIVATED BY 3 DIFFERENT EPH FAMILY LIGANDS

The Eph family of receptors, the largest subgroup within the tyrosine protein kinase receptor family, are comprised of at least thirteen mem bers, many of which are predominantly expressed in the developing and adult nervous system. In this study, we have isolated a full-length cD NA, encoding the mouse homologue of a previous partially characterized Eek protein, a member of Eph receptor tyrosine kinase family. In a co mparison of the amino acid sequences of various Eph family members, Ee k is most similar to Ehk-3/MDK1, Sek/Cek8, Ehk-2, Hek/Mek4/Cek4, and B sk/Ehk1/Rek7/Cek7, which are predominantly expressed in the nervous sy stem. Additionally, we have used a low-stringency PCR cloning techniqu e to identify ligands, related to B61, that may interact with Eek. Thr ee different GPI-linked ligands, namely Elf-1/Cek7-L, Ehk1-L/Efl-2/Ler k3 and AL-1/RAGS, were isolated from mouse brain. To study the functio nal interactions between these ligands and the Eek receptors, rye have constructed chimeric ligands consisting of the Fc portion of human Ig G fused to their carboxyl-terminus. These chimeric ligands bound to, a nd activated both the Eek receptors and the Eek-TrkB chimeric receptor s expressed in NIH3T3 cells. These findings suggest that Eek receptor can be activated by at least three different GPI-Linked ligands.