Description: This 22E5 monoclonal antibody reacts with the extracellular domain of mouse Notch1, 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 1 is expressed on thymocytes, bone marrow hematopoietic stem cells, T and NK cells. Lower Notch1 expression levels can be found on B cells and monocytes. Studies show that some subsets of T-cell acute lymphoblastic leukemia (T-ALL) arise due to Notch1 chromosomal translocation with TCRβ, which results in the expression of constitutively active Notch1. This cell surface receptor is involved in T cell lineage commitment, thymocyte development, and Th2 differentiation.
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