The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Delta or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Core pathway components are required for signaling from the sending cell and response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).