Description: This HMN4-14 monoclonal antibody reacts with mouse Notch4, 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, forms a ternary complex with the DNA-binding transcription factor CSL (CBF-1, Su(H), Lag-1) and the coactivator Mastermind, and ultimately activates transcription.
Notch 4 has been shown to be expressed in CD8+ splenic dendritic cells, endothelial cells (e.g. vascular smooth muscle cells), and macrophages. A truncated, constitutively active form of Notch 4 designated Int3 also exists in mice as a result of the mouse mammary tumor virus (MMTV) insertion into the Notch 4 gene. Composed of the transmembrane and intracellular domains of Notch 4, Int3 has been reported to be involved in mammary gland development and tumorigenesis in the mouse. Finally, studies have shown Notch 4 involvement in myeloid proliferation, hematopoiesis, and embryonic endothelial development.
The HMN4-14 antibody is reported to also crossreact to rat and have activating properties.
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