Description: This MNH3-21 monoclonal antibody reacts with the extracellular domain of human 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.
Notch3 expression has been demonstrated on some thymocyte subsets, including CD4-CD8- and CD8SP cells. This Notch receptor is also expressed on vascular smooth muscle and cells of the central nervous system. In addition to its role in stem cell hematopoiesis, Notch3 plays a pivotal role in T cell lineage commitment and thymocyte development. Moreover, Notch3 is overexpressed in human T-cell acute lymphoblastic leukemias (T-ALL) and other cancers. Finally, mutation of Notch3 has been linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a CNS degenerative disorder.
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