HAMSTER ANTI MOUSE DELTA-LIKE PROTEIN 4:RPE

Hamster anti Mouse Delta-Like Protein 4 antibody, clone HMD4-2 recognizes mouse Delta-like protein 4 (DLL4), one of the five major ligands of the Notch signalling pathway, which is activated through the binding of specific ligands to the Notch receptors Notch 1-4.The Notch signalling pathway is an evolutionarily conserved pathway in multi-cellular organisms, which is vital for cell-cell communication, important during fundamental developmental and physiological processes, including regulation of cell fate decisions during neuronal, cardiac and endocrine development, stem cell haematopoiesis, thymic T-cell development, and both tumour progression and suppression.Ligation of Notch receptors by their specific ligands, Jagged1 (CD339), Jagged2, Delta like-1 (DLL1), DLL3 and DLL4, on physically adjacent signal receiving cells, induces proteolysis of the receptors by ADAM-family metalloproteases and gamma-secretase complex, within the transmembrane domain, releasing the Notch intracellular domain (NICD) to translocate to the nucleus. Subsequent signal transduction then occurs through either the CSL-NICD-Mastermind complex cascade (canonical pathway), or NF-kappaB-NICD and CSL-NICD-Deltex complex signalling cascades (non-canonical pathway). The canonical pathway inhibits the differentiation of stem cells or progenitor cells, whilst the non-canonical pathway promotes differentiation.DLL4 is expressed by vascular endothelium, and plays a vital role in embryonic vascular development. DLL4 signalling has been shown to play a role in the angiogenesis of clear-cell renal tumours, and pancreatic, bladder and colonic cancer. Studies have shown that DLL4 expression in endothelium cells, can be up-regulated by vascular endothelial growth factor (VEGF) and basic-FGF, and by HIF1 alpha, and that blockade of DLL4 inhibits tumour growth by promoting non-productive angiogenesis.