Ligand binding induces a conformational change in NOTCH2, through mechanical pulling of NOTCH triggered by endocytosis of the receptor-attached ligand (Meloty-Kapella et al. 2012). This conformational change exposes the S2 site in the extracellular region of NOTCH2 and results in cleavage of NOTCH2 by ADAM10 metalloprotease (Gibb et al. 2010, Groot et al. 2014), generating the membrane-anchored NOTCH2 fragment NEXT2 (Shimizu et al. 2000). The extracellular NOTCH2 portion remains attached to the ligand presented on the plasma membrane of a neighboring cell.
Kanda, Y, Kurokawa, M, Shimizu, K, Hirai, H, Kumano, K, Hamada, Y, Saito, T, Chiba, S, Hosoya, N
Botvinick, E, Meloty-Kapella, L, Weinmaster, G, Shergill, B, Kuon, J
Groot, AJ, Habets, R, Vooijs, M, Saftig, P, Hodin, CM, Theys, J, Reiss, K, Yahyanejad, S
Tew, JG, Gibb, DR, Rowe, WJ, Dempsey, PJ, Kang, DJ, Cichy, J, Conrad, DH, Crawford, HC, Yagita, H, El Sayed, R, El Shikh, M
metallopeptidase activity of ADAM10:Zn2+ [plasma membrane]
© 2022 Reactome
