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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035998-06
Application #
3289570
Study Section
Genetics Study Section (GEN)
Project Start
1986-09-15
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Weizmann Institute of Science
Department
Type
DUNS #
City
Rehovot
State
Country
Israel
Zip Code
76100
McBride, H J; Sil, A; Measday, V et al. (2001) The protein kinase Pho85 is required for asymmetric accumulation of the Ash1 protein in Saccharomyces cerevisiae. Mol Microbiol 42:345-53
Zak, N B; Shilo, B Z (1992) Localization of DER and the pattern of cell divisions in wild-type and Ellipse eye imaginal discs. Dev Biol 149:448-56
Klambt, C; Glazer, L; Shilo, B Z (1992) breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. Genes Dev 6:1668-78
Raz, E; Shilo, B Z (1992) Dissection of the faint little ball (flb) phenotype: determination of the development of the Drosophila central nervous system by early interactions in the ectoderm. Development 114:113-23
Glazer, L; Shilo, B Z (1991) The Drosophila FGF-R homolog is expressed in the embryonic tracheal system and appears to be required for directed tracheal cell extension. Genes Dev 5:697-705
Raz, E; Schejter, E D; Shilo, B Z (1991) Interallelic complementation among DER/flb alleles: implications for the mechanism of signal transduction by receptor-tyrosine kinases. Genetics 129:191-201
Zak, N B; Wides, R J; Schejter, E D et al. (1990) Localization of the DER/flb protein in embryos: implications on the faint little ball lethal phenotype. Development 109:865-74
Zak, N B; Shilo, B Z (1990) Biochemical properties of the Drosophila EGF receptor homolog (DER) protein. Oncogene 5:1589-93
Wides, R J; Zak, N B; Shilo, B Z (1990) Enhancement of tyrosine kinase activity of the Drosophila epidermal growth factor receptor homolog by alterations of the transmembrane domain. Eur J Biochem 189:637-45
Schejter, E D; Shilo, B Z (1989) The Drosophila EGF receptor homolog (DER) gene is allelic to faint little ball, a locus essential for embryonic development. Cell 56:1093-104