NOTCH2 fragment:DSL DLL/JAG:NOTCH2 Notch 2-ligand complex is cleaved to produce NEXT2 Ligand binding induces a conformational change in the NOTCH2, probably through mechanical pulling of NOTCH2 triggered by endocytosis of receptor-attached ligand. This conformational change exposes the S2 site in the extracellular region of NOTCH2 and results in cleavage of NOTCH2 by ADAM10 metalloprotease, generating the membrane-anchored NOTCH2 fragment NEXT2. The extracellular NOTCH2 portion remains attached to the ligand presented on the plasma membrane of a neighboring cell. Pubmed10958687 Pubmed20156974 Reactome Database ID Release 43157629 Reactome, http://www.reactome.org ReactomeREACT_267