Mouse DLL4 / Delta4 Protein (His Tag)

Delta4

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Catalog Number	P50640-M08H
Organism Species	Mouse
Host	Human Cells
Synonyms	Delta4
Molecular Weight	The secreted recombinant mouse DLL4 comprises 509 amino acids and has a calculated molecular mass of 55.7 kDa. As a result of glycosylation, the recombinant protein migrates as an approximately 68 kDa band in SDS-PAGE under reducing conditions.
predicted N	Ser 28
SDS-PAGE
Purity	> 96 % as determined by SDS-PAGE
Protein Construction	A DNA sequence encoding the extracellular domain of mouse DLL4 (NP_062327.2) (Met 1-Pro 525) was expressed, with a C-terminal polyhistidine tag.
Bio-activity	1. Measured by its binding ability in a functional ELISA. Immobilized mouse DLL4-his (P50640-M08H) at 10 μg/mL (100 μL/well) can bind biotinylated mouse NOTCH1-his. The EC50 of biotinylated mouse NOTCH1-his is 30 ng/mL. 2. Measured by the ability of the immobilized protein to enhance BMP2-induced alkaline phosphatase activity in C3H10T1/2 mouse embryonic fibroblast cells. The ED50 for this effect is typically 0.2-3 µg/mL.
Research Area	Immunology |Signal Transduction |Notch Pathway
Formulation	Lyophilized from sterile PBS, pH 7.4 1. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween80 are added as protectants before lyophilization. Specific concentrations are included in the hardcopy of COA.
Background	Delta-like protein 4 (DLL4, Delta4), a type I membrane-bound Notch ligand, is one of five known Notch ligands in mammals and interacts predominantly with Notch 1, which has a key role in vascular development. Recent studies yield substantial insights into the role of DLL4 in angiogenesis. DLL4 is induced by vascular endothelial growth factor (VEGF) and acts downstream of VEGF as a 'brake' on VEGF-induced vessel growth, forming an autoregulatory negative feedback loop inactivating VEGF. DLL4 is downstream of VEGF signaling and its activation triggers a negative feedback that restrains the effects of VEGF. Attenuation of DLL4/Notch signaling results in chaotic vascular network with excessive branching and sprouting. DLL4 is widely distributed in tissues other than vessels including many malignancies. Furthermore, the molecule is internalized on binding its receptor and often transported to the nucleus. In pathological conditions, such as cancer, DLL4 is up-regulated strongly in the tumour vasculature. Blockade of DLL4-mediated Notch signaling strikingly increases nonproductive angiogenesis, but significantly inhibits tumor growth in preclinical mouse models. In preclinical studies, blocking of DLL4/Notch signaling is associated with a paradoxical increase in tumor vessel density, yet causes marked growth inhibition due to functionally defective vasculature. Thus, DLL4 blockade holds promise as an additional strategy for angiogenesis-based cancer therapy.
Reference	Yan M, et al. (2007) Delta-like 4/Notch signaling and its therapeutic implications. Clin Cancer Res. 13(24): 7243-6. Sainson RC, et al. (2007) Anti-Dll4 therapy: can we block tumour growth by increasing angiogenesis? Trends Mol Med. 13(9): 389-95. Martinez JC, et al. (2009) Nuclear and membrane expression of the angiogenesis regulator delta-like ligand 4 (DLL4) in normal and malignant human tissues. Histopathology. 54(5): 598-606. Li JL, et al. (2010) Targeting DLL4 in tumors shows preclinical activity but potentially significant toxicity. Future Oncol. 6(7): 1099-103.