Notch, a cell surface receptor, is required for producing different types o
f cells during development of Drosophila melanogaster. Notch activates expr
ession of one set of genes in response to ligand Delta and another set of g
enes in response to ligand Wingless. The means by which Notch initiates the
se different intracellular activities was examined in this study. Cultured
cells expressing Notch were treated with Delta or Wingless, and the effect
on Notch was examined by Western blotting. Treatment of cells with Delta re
sulted in accumulation of similar to 120-kDa Notch intracellular domain mol
ecules in the cytoplasmic fraction. This form of Notch did not accumulate i
n cells treated with Wingless, but the similar to 350-kDa full-length Notch
molecules accumulated. These results indicate that N responds differently
to binding by Delta and Wingless, and suggest that although the Delta signa
l is transduced by the Notch intracellular domain released from the plasma
membrane, the Wingless signal is transduced by the Notch intracellular doma
in associated with the plasma membrane.