Notch4 (L5C5) Mouse mAb

Notch proteins (Notch1-4) are a family of transmembrane receptors that play important roles in development and the determination of cell fate (1). Mature Notch receptors are processed and assembled as heterodimeric proteins, with each dimer composed of a large extracellular ligand-binding domain, a single-pass transmembrane domain, and a smaller cytoplasmic subunit (Notch intracellular domain, NICD) (2). Binding of Notch receptors to ligands of the Delta-Serrate-Lag2 (DSL) family triggers heterodimer dissociation, exposing the receptors to proteolytic cleavages; these result in release of the NICD, which translocates to the nucleus and activates transcription of downstream target genes (3,4).Notch4 is primarily expressed in endothelial cells and is processed similarly to Notch1 (5-7). The mouse Notch4 gene (also known as Int-3) is a frequent target in Mouse Mammary Tumour Virus (MMTV)-induced mammary tumors (6,8). The intracellular domain of Notch4 binds to Smad3 and inhibits TGF-β signaling (9). 1.Artavanis-Tsakonas, S. et al. (1999) Science 284, 770-6. 2.Chan, Y.M. and Jan, Y.N. (1998) Cell 94, 423-6. 3.Schroeter, E.H. et al. (1998) Nature 393, 382-6. 4.Rand, M.D. et al. (2000) Mol Cell Biol 20, 1825-35. 5.Uyttendaele, H. et al. (1996) Development 122, 2251-2259. 6.Shirayoshi, Y. et al. (1997) Genes Cells 2, 213-224. 7.Baron, M. (2003) Semin. Cell Dev. Biol. 14, 113-119. 8.Gallahan, D. and Callahan, R. (1997) Oncogene 14, 1883-1890. 9.Sun, Y. et al. (2005) Oncogene 24, 5365-5374.