Further evidence for function of the Drosophila Notch protein as a transmembrane receptor.
N locus mutations associated with unusual mutant phenotypes were found to alter the structure of the encoded protein. Two mutations, NCo and N60g11, eliminate much of the cytoplasmic domain. NCo can act as a null allele or as a competitive inhibitor of N+ function, whereas N60g11 produces dominant gain of function in some cell types. This difference in function can be attributed to retention of cdc10/SWI6 repeats in the Notch60g11 protein. The results suggest a role for these repeats in intracellular signaling and are consistent with action of Notch as a receptor. nd3 and l(1)NB alter extracellular epidermal growth factor-like and lin-12/Notch elements, respectively. nd3 eliminates a conserved cysteine residue, so the mutation may result in complete loss of function for a single Notch epidermal growth factor element. N60g11 and l(1)NB produce related gain-of-function phenotypes. It is proposed that l(1)NB produces an extracellular modification of the protein that stimulates aberrant intracellular signaling by the Notch cytoplasmic domain.
Lyman
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Laboratory of Genetics, Rockefeller University, New York, NY 10021.
Young
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D005838:Genotype; D006720:Homozygote; D007301:Insect Hormones / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D051880:Receptors, Notch; D015183:Restriction Mapping; D017384:Sequence Deletion; D013489:Suppression, Genetic; D014965:X-Rays
D029721:Drosophila Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch