Delta-Notch signaling pathway (WP946)

There are 4 Notch receptors in humans (Notch 1-4) that bind to a family of 5 ligands (Jagged 1 and 2 and Delta-like 1-3). The Notch receptors are expressed on the cell surface as heterodimeric proteins and their ligands are also membrane-bound. Signaling through the Notch receptors is triggered by ligand-binding that induces cleavage of the extracellular domain by an ADAM family metalloprotease followed by a cleavage within the transmembrane domain by gamma secretase complex. The second cleavage leads to translocation of the cytosolic domain of Notch receptors into the nucleus. Notch proteins are important in lineage specification and stem cell maintenance. Aberrant Notch signaling has been linked to a number of malignancies including leukemias, lymphomas and carcinomas of the breast, skin, lung, cervix and kidneys. Source: NetPath http://www.netpath.org/pathways?path_id=NetPath_3

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