Recombinant Mouse Notch-1 Fc Chimera Protein, CF

Notch-1 is a 300 kDa type I transmembrane glycoprotein that is one of four Notch homologues involved in developmental processes (1 - 3). Notch signaling is important for maintaining stem cells and inducing differentiation, especially in the nervous system and lymphoid tissues (2 - 4). Notch can specify binary cell fates. For example, it promotes T-cell over B-cell development from a common precursor (2). Mouse Notch-1 is synthesized as a 2531 amino acid (aa) precursor that contains an 18 aa signal sequence, a 1707 aa extracellular domain (ECD) with 36 EGF-like repeats and three Lin‑12/notch repeats (LNR), a 21 aa transmembrane (TM) segment and a 785 aa cytoplasmic domain that contains six ankyrin repeats, a glutamine-rich domain and a PEST sequence. The 11^th and 12^th EGF-like repeats, that bind ligands such as Jagged and Delta‑like families in humans, correspond to aa 412 - 488 in mouse Notch-1 (6). Elongation of O‑linked fucose chains by Fringe family members at a site within this region can inhibit the interaction of Notch with Jagged ligands, thereby promoting Delta‑like ligand interactions (7). The Notch-1 receptor undergoes post-translational furin-type proteolytic cleavage, generating a heterodimer through the interaction of a hydrophobic area C‑terminal to the LNR on the extracellular region with the transmembrane/cytoplasmic portion (8, 9). Upon ligand binding, additional sequential proteolysis by TNF-converting enzyme (ADAM17) and the presenilin-dependent gamma-secretase results in the release of the Notch intracellular domain (NICD) which translocates into the nucleus, activating transcription of Notch-responsive genes (10). Mouse Notch-1 ECD aa 19 - 526, which includes the first 13 EGF repeats, shows 94%, 91%, 86% and 79% aa identity with corresponding regions of rat, human, canine, and chicken Notch-1, respectively. This region also exhibits 55 - 58% aa identity with human Notch‑2 and Notch-3.