Rat Notch-1 Biotinylated Antibody

Rat Notch-1 is a 300 kDa, type I transmembrane glycoprotein involved in a number of early-event developmental processes (1). In both vertebrates and invertebrates, Notch signaling is important for specifying cell fates and for defining boundaries between different cell types. The molecule is synthesized as a 2531 amino acid (aa) precursor that contains an 18 aa signal sequence, a 1705 aa extracellular region, a 23 aa transmembrane (TM) segment and a 785 aa cytoplasmic domain (2). The large Notch-1 extracellular domain has 36 EGF‑like repeats followed by three notch/Lin-12 repeats. Of the 36 EGF‑like repeats, the 11^th and 12^th EGF‑like repeats have been shown to be both necessary and sufficient for binding the ligands Delta and Serrate, in Drosophila (3). The Notch-1 cytoplasmic domain contains six ankyrin repeats, a glutamine-rich domain and a PEST sequence. The Notch-1 receptor undergoes post-translational proteolytic cleavage by a furin-like enzyme to form a heterodimer of the 1635 aa ligand binding extracellular region and the 877 aa transmembrane protein (4). Upon ligand binding, additional sequential proteolysis by TNF-converting enzyme and the Presenilin-dependent gamma -secretase results in the release of the Notch intracellular domain (NCID) which translocates into the nucleus where it functions as a transcription activator to initiate transcription of Notch-responsive genes (5). An alternative Notch signaling pathway that is mediated by the full-length form of Notch that has not been cleaved by the furin-like enzyme has also been reported (6). The rat Notch-1 extracellular domain shows 86% and 97% aa identity to human and mouse Notch-1 extracellular domains respectively. It also exhibits 56% and 50% aa identity with rat Notch-2 and Notch-3 extracellular domains, respectively.