PathwayStep2822 PathwayStep2818 PathwayStep517 Notch 3-ligand complex is cleaved to produce NEXT3 PathwayStep5554 Notch 3 heterodimer binds with a Notch ligand in the extracellular space NEXT3 is cleaved to produce NICD3 NICD3 traffics to the nucleus Signaling by NOTCH3 Authored: Jassal, B, 2004-12-15 13:08:03 Edited: Orlic-Milacic, M, 2012-02-10 GENE ONTOLOGYGO:0007219 Reactome Database ID Release 431980148 Reactome, http://www.reactome.org ReactomeREACT_118862 Reviewed: Joutel, A, 2004-12-15 Similar to NOTCH1, NOTCH3 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH3, first by ADAM10 at the S2 cleavage site, then by gamma-secretase at the S3 cleavage site, resulting in the release of the intracellular domain of NOTCH3, NICD3, into the cytosol. NICD3 subsequently traffics to the nucleus where it acts as a transcriptional regulator.