PathwayStep2821 PathwayStep2817 PathwayStep516 Notch 2-ligand complex is cleaved to produce NEXT2 PathwayStep5552 Notch 2 heterodimer binds with a Notch ligand in the extracellular space NEXT2 is cleaved to produce NICD2 NICD2 traffics to the nucleus Signaling by NOTCH2 Authored: Jassal, B, 2004-12-15 13:08:03 Edited: Orlic-Milacic, M, 2012-02-10 GENE ONTOLOGYGO:0007219 Reactome Database ID Release 431980145 Reactome, http://www.reactome.org ReactomeREACT_118721 Reviewed: Joutel, A, 2004-12-15 Similar to NOTCH1, NOTCH2 is activated by delta-like and jagged ligands (DLL/JAG) expressed in trans on a neighboring cell. The activation triggers cleavage of NOTCH2, 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 NOTCH2, NICD2, into the cytosol. NICD2 subsequently traffics to the nucleus where it acts as a transcriptional regulator.