Molecular analysis of the Drosophila EGF receptor homolog reveals that several genetically defined classes of alleles cluster in subdomains of the receptor protein.
Mutations in the torpedo gene, which encodes the fruitfly homolog of the epidermal growth factor receptor (DER), disrupt a variety of developmental 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 oogenesis, torpedo is genetically complex: a number of alleles of the gene differentially affect the development of specific tissues, such as the eye, wing, bristles and ovary. In addition, torpedo mutations exhibit interallelic 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 differentially affect specific developmental processes encode receptors with altered extracellular domains. Alleles that fully or partially complement a wide range of embryonic and postembryonic torpedo mutations encode receptors with altered intracellular domains. From these findings we conclude the following. First, the torpedo protein may be activated by tissue-specific ligands. Second, the torpedo receptor tyrosine kinase may phosphorylate multiple substrates. Third, signal transduction by torpedo appears to require the physical association of receptors. Finally, the extracellular domain of the Torpedo protein may play an essential role in mediating receptor-receptor interactions.
Clifford
R
R
Department of Molecular Biology, Princeton University, New Jersey 08544-1003.
Schüpbach
T
T
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D017344:Genes, Insect; D005804:Genes, Lethal; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D005810:Multigene Family; D016296:Mutagenesis; D010766:Phosphorylation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D066246:ErbB Receptors