LIGANDS FOR THE RECEPTOR TYROSINE KINASES HEK AND ELK - ISOLATION OF CDNAS ENCODING A FAMILY OF PROTEINS

Hek is a member of the eph subfamily of receptor tyrosine kinases whos e members include elk, hek2, sek, eph and eck among others. Using a so luble form of hek consisting of the extracellular region of the recept or fused to the Fc domain of human IgG1 and an expression cloning stra tegy, we have isolated two different but related cDNAs from the human T-lymphoma line HSB-2 that encode ligands for hek. The cDNAs encode pr oteins of 238 and 201 amino acids (44% amino acid identity) that are a nchored to the membrane by glycosyl-phosphatidylinositol (GPI)-linkage . The proteins encoded by these cDNAs are bound by hek with affinity c onstants of 2 x 10(8) m(-1). These proteins also bind the elk tyrosine kinase receptor. These cDNAs are related to other cDNAs that we have recently isolated from a human placental library that encode ligands f or both hek and elk and define an emerging family of ligands for eph-r elated kinases (LERKs).