MOLECULAR ANALYSIS OF THE DROSOPHILA EGF RECEPTOR HOMOLOG REVEALS THAT SEVERAL GENETICALLY DEFINED CLASSES OF ALLELES CLUSTER IN SUBDOMAINSOF THE RECEPTOR PROTEIN

Mutations in the torpedo gene, which encodes the fruitfly homolog of t he epidermal growth factor receptor (DER), disrupt a variety of develo pmental processes in Drosophila. These include the survival of certain embryonic ectodermal tissues, the proliferation of the imaginal discs , the morphogenesis of several adult ectodermal structures and oogenes is. torpedo is genetically complex: a number of alleles of the gene di fferentially affect the development of specific tissues, such as the e ye, wing, bristles and ovary. In addition, torpedo mutations exhibit i nterallelic complementation. Molecular analysis of 24 loss-of-function mutations in the torpedo gene provides insights into the mechanistic basis of its genetic complexity. We observe an intriguing correlation between molecular lesions and mutant phenotypes. Alleles that differen tially affect specific developmental processes encode receptors with a ltered extracellular domains. Alleles that fully or partially compleme nt a nide range of embryonic and postembryonic torpedo mutations encod e receptors with altered intracellular domains. From these findings we conclude the following. First, the torpedo protein may be activated b y tissue-specific ligands. Second, the torpedo receptor tyrosine kinas e may phosphorylate multiple substrates. Third, signal transduction by torpedo appears to require the physical association of receptors. Fin ally, the extracellular domain of the Torpedo protein may play an esse ntial role in mediating receptor-receptor interactions.