Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor.
The Notch gene of Drosophila plays an important role in cell fate specification throughout development. To investigate the functions of specific structural domains of the Notch protein in vivo, a series of deletion mutants have been ectopically expressed under the hsp70 heat shock promoter. Two classes of dominant phenotypes are observed, one suggestive of Notch loss-of-function mutations and the other of Notch gain-of-function mutations. Dominant activated phenotypes result from overexpression of a protein lacking most extracellular sequences, while dominant negative phenotypes result from overexpression of a protein lacking most intracellular sequences. These results support the notion that Notch functions as a receptor whose extracellular domain mediates ligand binding, resulting in the transmission of developmental signals by the cytoplasmic domain. Finally, the phenotypes observed suggest that the cdc 10/ankyrin repeat region within the intracellular domain plays an essential role in the postulated signal transduction events.
Rebay
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Howard Hughes Medical Institute, Department of Cell Biology, Yale University, New Haven, Connecticut 06536-0812.
Fehon
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Artavanis-Tsakonas
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D000818:Animals; D017487:Ankyrins; D002451:Cell Compartmentation; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins / Q000235:genetics; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014157:Transcription Factors
D017487:Ankyrins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C061178:cdc10 protein, S pombe