DLL4 (D7N3H) Rabbit mAb

Notch signaling is activated upon engagement of the Notch receptor with its ligands, the DSL (Delta, Serrate, Lag2) proteins of single-pass type I membrane proteins. The DSL proteins contain multiple EGF-like repeats and a DSL domain that is required for binding to Notch (1,2). Five DSL proteins have been identified in mammals: Jagged1, Jagged2, Delta-like (DLL) 1, 3 and 4 (3). Ligand binding to the Notch receptor results in two sequential proteolytic cleavages of the receptor by the ADAM protease and the γ-secretase complex. The intracellular domain of Notch is released and then translocates to the nucleus where it activates transcription. Notch ligands may also be processed in a way similar to Notch, suggesting a bi-directional signaling through receptor-ligand interactions (4-6).DLL4 expression is highly restricted to the vascular endothelium (7), and haploinsufficiency of DLL4 results in major defects in vascular systems in mouse (8-11). Blockade of DLL4 inhibits tumor growth in model systems (12-14). 1.Wilson, A. and Radtke, F. (2006) FEBS Lett. 580, 2860-2868. 2.Hansson, E.M. et al. (2004) Semin. Cancer Biol. 14, 320-328. 3.Chiba, S. (2006) Stem Cells 24, 2437-2447. 4.Bland, C.E. et al. (2003) J. Biol. Chem. 278, 13607-13610. 5.Six, E. et al. (2003) Proc. Natl. Acad. Sci. USA 100, 7638-7643. 6.LaVoie, M.J. and Selkoe, D.J. (2003) J. Biol. Chem. 278, 34427-34437. 7.Shutter, J.R. et al. (2000) Genes Dev 14, 1313-8. 8.Gale, N.W. et al. (2004) Proc Natl Acad Sci U S A 101, 15949-54. 9.Krebs, L.T. et al. (2004) Genes Dev 18, 2469-73. 10.Duarte, A. et al. (2004) Genes Dev 18, 2474-8. 11.Hellström, M. et al. (2007) Nature 445, 776-80. 12.Noguera-Troise, I. et al. (2006) Nature 444, 1032-7. 13.Lobov, I.B. et al. (2007) Proc Natl Acad Sci U S A 104, 3219-24. 14.Scehnet, J.S. et al. (2007) Blood 109, 4753-60.