Recombinant Human DLL4 Fc Chimera Protein, CF

Recombinant Human DLL4 Fc Chimera (Catalog # 10185‑D4)enhances Recombinant Human BMP-2 (Catalog # 355-BM) induced alkalinephosphatase activity in the C3H10T1/2 mouse embryonic fibroblast cell line. TheED50 for this effect is 0.02‑0.12 μg/mL.

2 μg/lane of Recombinant Human DLL4 Fc Chimera was resolved with SDS-PAGE under reducing (R) and non-reducing (NR) conditions and visualized by Coomassie® blue staining, showing bands at 88-98 kDa and 170-190 kDa, respectively.

• Reactivity: Hu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Human DLL4 Fc Chimera Protein, CF Summary

• Details of Functionality: Measured by the ability of the immobilized protein to enhance BMP-2 induced alkaline phosphatase activity in C3H10T1/2 mouse embryonic fibroblast cells. Nobta, M. et al. (2005) J. Biol. Chem. 280:15842. The ED₅₀ fort his effect is 0.02-0.12 μg/mL.
• Source: Human embryonic kidney cell, HEK293-derived human DLL4 protein
  

  Human DLL4 (Ser27-Pro524) Accession # Q9NR61	IEGRMDP	Human IgG1 (Pro100-Lys330)
  N-terminus		C-terminus

• Accession #: Q9NR61
• N-terminal Sequence: Ser27
• Structure / Form: Disulfide-linked homodimer
• Protein/Peptide Type: Recombinant Proteins
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 81 kDa.
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 88-98 kDa, under reducing conditions

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS.
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 250 μg/mL in PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human DLL4 Fc Chimera Protein, CF

• Delta 4 precursor
• delta 4
• delta ligand 4
• delta4
• delta-like 4 (Drosophila)
• delta-like 4 homolog (Drosophila)
• delta-like 4 homolog
• delta-like 4 protein
• delta-like protein 4
• DLL4
• Drosophila Delta homolog 4
• hdelta2
• MGC126344
• notch ligand delta-2
• notch ligand DLL4

Background

Delta-like protein 4 (DLL4) is a type I membrane protein belonging to the Delta/Serrate/Lag2 (DSL) family of Notch ligands (1). Notch signaling is an evolutionarily conserved pathway that controls cell fate and is required in multiple developmental processes including vascular development, hematopoiesis, somatogenesis, myogenesis, and neurogenesis (2-4). Dysregulation in the Notch pathway is associated with various human diseases. In mammals, four Notch homologs (Notch 1 to 4) and five ligands (DLL 1, 3 and 4, Jagged 1 and 2) have been identified. Notch ligands are transmembrane proteins with a DSL motif necessary for Notch binding, tandem EGF repeats, a transmembrane region and a short intracellular domain (ICD). Notch ligands are categorized into two subfamilies based on the presence of an extracellular cysteine-rich domain and insertions that interrupt some EGF repeats in the Jagged but not the Delta ligand family. Interactions of Notch receptors with their ligands results in reciprocal regulated intramembrane proteolysis (RIP) (4). RIP is a mechanism for transmembrane signal transduction that involves the sequential processing by a disintegrin metalloprotease (ADAM) and then by presenilin/ gamma secretase, resulting in shedding of the extracellular domains and the generation of the soluble ICD signaling fragments, respectively. The Notch ICD translocates to the nucleus and interacts with transcriptional coactivators, resulting in the transcription of target genes. The ICDs of the Notch ligands have also been shown to translocate to the nucleus where they may have a signaling function (5, 6). DLL4 is expressed highly and selectively within the arterial endothelium and has been shown to function as a ligand for Notch 1 and Notch 4. Human and mouse DLL4 share 86% amino acid sequence identity (1).

1. Shutter, J.R. et al. (2000) Genes Dev. 14:1313.
2. Iso, Tatsuya et al. (2002) Arterioscler. Thromb. Vasc. Biol. 23:543.
3. Walker, L. et al. (2001) Stem Cells 19:543.
4. Baron, M. (2002) Semin. Cell Dev. Biol. 14:113.
5. Ikeuchi, T. and S.S. Sisodia (2003) J. Biol. Chem. 278:7751.
6. Bland, C.E. et al. (2003) J. Biol. Chem. 278:13607.

Publications for DLL4 (10185-D4)(4)

Publications using 10185-D4

• Smith, MH;Gao, VR;Periyakoil, PK;Kochen, A;DiCarlo, EF;Goodman, SM;Norman, TM;Donlin, LT;Leslie, CS;Rudensky, AY; Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis Nature immunology 2023-06-05 [PMID: 37277655] (Bioassay, Human)
• K Sottoriva, NY Paik, Z White, T Bandara, L Shao, T Sano, K Pajcini Notch-IL21 signaling axis primes bone marrow T cell progenitor expansion JCI Insight, 2022-05-09;0(0):. 2022-05-09 [PMID: 35349492] (Bioassay, Human)
• B Schmidl, M Siegl, M Boxberg, F Stögbauer, D Jira, C Winter, L Stark, A Pickhard, B Wollenberg, M Wirth NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC Cancers, 2022-02-21;14(4):. 2022-02-21 [PMID: 35205828] (Bioassay, Human)
• K Wei, I Korsunsky, JL Marshall, A Gao, GFM Watts, T Major, AP Croft, J Watts, PE Blazar, JK Lange, TS Thornhill, A Filer, K Raza, LT Donlin, CW Siebel, CD Buckley, S Raychaudhu, MB Brenner Notch signalling drives synovial fibroblast identity and arthritis pathology Nature, 2020-04-22;582(7811):259-264. 2020-04-22 [PMID: 32499639] (Bioassay, Human)

Bioinformatics

• Uniprot:
  • Q9NR61()