Description: This HMN3-133 monoclonal antibody reacts with mouse Notch3, one of four members of the Notch family of receptors. Notch receptors are 300-kDa single-pass transmembrane proteins. While the extracellular domain contains numerous epidermal growth factor-like repeats for ligand binding, the intracellular domain is involved in cell signaling. Upon binding its membrane-bound ligand (either Delta or Jagged), the Notch receptor undergoes proteolytic cleavage, first by ADAM-family metalloproteases and then by γ-secretase. The second cleavage event releases the Notch intracellular domain (NICD), which subsequently translocates into the nucleus, heterodimerizes with the DNA-binding protein RBP-J, recruits co-activator molecules, and ultimately activates transcription.
Notch 3 expression has been demonstrated on regulatory T cells and some thymocyte subsets, including CD4-CD8- and CD8SP cells. In addition, this Notch receptor is prevalent in vascular smooth muscle and the central nervous system. In addition to its role in stem cell hematopoiesis, Notch 3 plays a pivotal role in mammalian T cell lineage commitment and thymocyte development. Specifically, Notch 3 has been implicated in the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition with greatest expression in DN3 (CD4-CD8-CD25+CD44-) cells. Notch 3 may also be involved in regulating the pre-TCR checkpoint via crosstalk with the NFkappaB and E2A signaling pathways. Finally, overexpression of Notch 3 has been implicated in leukemia.
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