Notch Isoform Antibody Sampler Kit

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).Constitutively activated Notch1 signaling is associated with the majority of cases of T cell acute lymphoblastic leukemia (T-ALL). The activation is either due to mutations in Notch1 itself or in the components of ubiquitin ligase complex, namely FBW7 (5-6). Notch2 is a member of the Notch family and mutation in Notch2 is associated with Alagille syndrome (7). Notch3 is a member of the Notch family and is processed similar to Notch1 (8). It is expressed primarily in arterial smooth muscle cells (SMC). Mutations altering the number of cysteine residues in the notch3 extracellular region are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary angiopathy leading to strokes and dementia in adults (9-11). Recent studies indicate that Notch3 is overexpressed in many types of cancer (12-14). 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.Weng, A.P. et al. (2004) Science 306, 269-71. 6.Thompson, B.J. et al. (2007) J Exp Med 204, 1825-35. 7.McDaniell, R. et al. (2006) Am J Hum Genet 79, 169-73. 8.Baron, M. (2003) Semin Cell Dev Biol 14, 113-9. 9.Kalimo, H. et al. (2002) Brain Pathol 12, 371-84. 10.Karlström, H. et al. (2002) Proc Natl Acad Sci U S A 99, 17119-24. 11.Monet, M. et al. (2007) Hum Mol Genet 16, 982-92. 12.Park, J.T. et al. (2006) Cancer Res 66, 6312-8. 13.Gramantieri, L. et al. (2007) Liver Int 27, 997-1007. 14.Yamaguchi, N. et al. (2008) Cancer Res 68, 1881-8.