Human DLL4 / Delta-like 4 Protein

Delta-like 4,hdelta2

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Catalog Number	P10171-HCCH
Organism Species	Human
Host	Human Cells
Synonyms	Delta-like 4,hdelta2
Molecular Weight	The recombinant human DLL4 consists of 504 amino acids and predicts a molecular mass of 55 kDa.
predicted N	Ser 27
SDS-PAGE
Purity	> 95 % as determined by SDS-PAGE.
Protein Construction	A DNA sequence encoding the human DLL4 (NP_061947.1) (Met1-Pro524) was expressed with five amino acids (DDDDK) at the C-terminus.
Bio-activity
Research Area	Immunology |Signal Transduction |Notch Pathway
Formulation	Lyophilized from sterile PBS, pH 7.4. 1. Normally 5 % - 8 % trehalose and mannitol 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.