A Drosophila gene showing a high degree of similarity to the mammalian EGF and neu receptors (termed DER) has been isolated and characterized at the DNA, RNA and protein levels. Mutants in the gene were isolated, and shown to be allelic to the known """"""""faint little ball"""""""" and """"""""torpedo"""""""" mutations. The proposed research focuses on a detailed study of the gene at the genetic level, and of the protein at the biochemical level. These studies should have wide implications to the study of tysosine kinase receptors in Drosophila and in vertebrates. Specifically, the following approaches will be pursued: Over 20 mutant alleles of the gene are available. They include amorphs and hypomorphs. The lethal embryonic phenotype would be studied in detail to gain insights to the function of the gene. Interesting hypomorphic alleles have a viable adult phenotype, providing a powerful way to screen for second site suppressors of this phenotype. At the biochemical level, tentative evidence was obtained for the interaction of DER with another, species specific protein. This approach would be pursued, and the DER sites interacting with this putative protein identified. A 90kd Drosophila protein is specifically phosphorylated by and immunoprecipitated with a DER construct containing a mutation analogous to the neu oncogenic transmembrane mutation. This is a good candidate for a DER regulator or substrate, and will be characterized in detail. Finally, six new tyrosine kinase genes from Drosophila have been isolated, and will be studies in an attempt to identify more tyrosine kinases controlling specific developmental switches.
