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, N(Co) a nd N60g11, eliminate much of the cytoplasmic domain. N(Co) can act as a null allele or as a competitive inhibitor of N+ function, whereas N6 0g11 Produces dominant pin of function in some cell types. This differ ence in function can be attributed to retention of cdc10/SWI6 repeats in the Notch60g11 protein. The results suggest a role for these repeat s in intracellular signaling and are consistent with action of Notch a s a receptor. nd3 and l(1)N(B) alter extracellular epidermal growth fa ctor-like and lin-12/Notch elements, respectively. nd3 eliminates a co nserved cysteine residue, so the mutation may result in complete loss of function for a single Notch epidermal growth factor element. N60g11 and l(1)N(B) produce related gain-of-function phenotypes. It is propo sed that l(1)N(B) produces an extracellular modification of the protei n that stimulates aberrant intracellular signaling by the Notch cytopl asmic domain.