The long-term objectives of this research proposal are to define the functional roles of Drosophila src-family oncogenes during development. We have concentrated our attention on two members of this gene family: the Drosophila src28C gene and Drosophila epidermal growth factor receptor (DER) gene. Recently completed analysis of the src28C cDNA sequence revealed unique structural aspects of the encoded protein. The protein is more basic than other src-family proteins, with a pI of greater than 10, it has a glycine-rich amino-terminus, and a pattern of conserved amino acids reminiscent of both tyrosine and serine/threonine kinases. Although the capacity of many src- family oncogenes to cause disease when mutated has been well established, the normal physiological roles of these genes have not been revealed. We will study the participation of the src-28C gene in normal development. The DER gene is the only example of a potential mitotic signalling protein in Drosophila. The hypothetical mitotic signalling function of the Drosophila EGF receptor homolog will be tested through the experiments described in this proposal. Therefore the definition of the functional roles of these genes will contribute to knowledge of cellular oncogene function and of Drosophila development.
The Specific Aims of this proposal are to: (1) Complete in situ hybridization studies on the expression of src28c and DER RNA during embryogenesis and metamorphosis. (2) Isolate temperature-sensitive mutations in the src28C and DER genes to study their functional roles in cells and tissues where we have documented their expression. (3) Generate site-directed mutations in the src28C and DER genes to study the effect of mutations in specific regions of the proteins. (4) Determine the enzymatic activities of the proteins encoded by the src28C and DER genes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035911-05
Application #
3173435
Study Section
Molecular Biology Study Section (MBY)
Project Start
1984-08-01
Project End
1990-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
01545
Theroux, S J; Wadsworth, S C (1992) Protein-tyrosine kinase activity of alternate protein products of the Drosophila Dsrc28C locus. FEBS Lett 311:1-6
Wadsworth, S C; Muckenthaler, F A; Vincent 3rd, W S (1990) Differential expression of alternate forms of a Drosophila src protein during embryonic and larval tissue differentiation. Dev Biol 138:296-312
Wadsworth, S C (1990) Drosophila src family proteins. Comp Biochem Physiol B 97:403-6
Vincent 3rd, W S; Gregory, R J; Wadsworth, S C (1989) Embryonic expression of a Drosophila src gene: alternate forms of the protein are expressed in segmental stripes and in the nervous system. Genes Dev 3:334-47
Wadsworth, S C; Rosenthal, L S; Kammermeyer, K L et al. (1988) Expression of a Drosophila melanogaster acetylcholine receptor-related gene in the central nervous system. Mol Cell Biol 8:778-85
Gregory, R J; Kammermeyer, K L; Vincent 3rd, W S et al. (1987) Primary sequence and developmental expression of a novel Drosophila melanogaster src gene. Mol Cell Biol 7:2119-27