NOTCH3:DSL NOTCH3 fragment:DSL Notch 3-ligand complex is cleaved to produce NEXT3 Ligand binding induces a conformational change in the NOTCH3, probably through mechanical pulling of NOTCH3 triggered by endocytosis of receptor-attached ligand. This conformational change exposes the S2 site in the extracellular region of NOTCH3 and results in cleavage of NOTCH3 by ADAM10 metalloprotease, generating the membrane-anchored NOTCH3 fragment NEXT3. The extracellular NOTCH3 portion remains attached to the ligand presented on the plasma membrane of a neighboring cell. Pubmed10882063 Pubmed10958687 Pubmed12794186 Reactome Database ID Release 43157626 Reactome, http://www.reactome.org ReactomeREACT_1552