cDNA cloning and characterization of ligands for the Eck/Eph receptor protein-tyrosine kinases.

Abstract

Receptor protein-tyrosine kinases (RPTKs) are fundamentally important in mediating cell proliferation, differentiation and development. Binding of a ligand to its cognate receptor leads to initiation of a signal transduction cascade that is eventually responsible for the observed biological effect. The Eck/Eph subfamily consists of 13 orphan receptors for which ligands await discovery. In this study, ligands for the Cek5 and Cek7 RPTKs (members in Eph/Eck RPTKs subfamily) were cloned using an expression cloning strategy. These ligands were shown to be able to bind and activate their cognate receptors. B61, the ligand for the Eck RPTK was characterized biochemically and developmentally. It was shown that B61 existed as a glycosylphosphatidylinositol-linked cell surface protein capable of inducing activation of its cognate receptor. In addition, the function of B61 was studied in keratinocytes where it was found to have a growth inhibitory influence.