Characterization of the expression of the Cek8 receptor-type tyrosine kinase during development and in tumor cell...

Cek8 is a receptor-type tyrosine kinase gene that was identified by screening a 10 day chicken embryo library with a DNA probe corresponding to the related kinase Cek4 (Sajjadi & Pasquale, 1993). Here we report the characterization of the Cek8 protein and its expression in embryonic tissues and tumor cell lines. The 120 kd Cek8 protein is detected early in embryogenesis, is developmentally regulated and preferentially, but not exclusively, expressed in neural tissues. In the stage 24 chick embryo, Cek8 immunoreactivity is prominent in the spinal cord and spinal nerves. At embryonic day 6, Cek8 expression becomes concentrated to the ventral portion of the spinal nerves, suggesting a role in axonogenesis of specific subsets of neurons. Cek8 is expressed in nearly all of the tumor cell lines examined, including cell lines derived from tumors of the central nervous system. Although the phosphorylation on tyrosine of Cek8 during development is moderate or undetectable, Cek8 is substantially phosphorylated on tyrosine (and thus presumably activated) in many of the transformed cell lines. Because of its high frequency of expression in tumor cell lines, Cek8 differs from previously investigated Eph-related kinases. However, as we show, Cek8 is not unique among the Eph-related kinases: another member of the Eph subclass, Cek5, has similar patterns of expression and phosphorylation in tumor cells. Based on its binding to a variety of lectin columns, Cek8 contains complex N-linked oligosaccharides. Cross-linking of Cek8 molecules on the cell surface with wheat germ agglutinin caused their rapid phosphorylation on tyrosine. Autophosphorylation on tyrosine is typically the first step in the activation of a receptor tyrosine kinase by a ligand.