Cell Signaling Technology

Product Pathways - Wnt / Hedgehog / Notch

DLL4 Antibody #2589

Applications Reactivity Sensitivity MW (kDa) Source
W IP H Endogenous 75-80 kDa Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

DLL4 Antibody detects endogenous levels of total DLL4 protein.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to a region surrounding residue Leu617 of human DLL4. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from HUVEC and COS cells, untransfected or transiently transfected with a construct expressing human DLL4, using DLL4 Antibody.

Background

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 similiar 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, 1313-1318.
  8. Gale, N.W. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 15949-15954.
  9. Krebs, L.T. et al. (2004) Genes Dev. 18, 2469-2473.
  10. Duarte, A. et al. (2004) Genes Dev. 18, 2474-2478.
  11. Hellström, M. et al. (2007) Nature 445, 776-780.
  12. Noguera-Troise, I. et al. (2006) Nature 444, 1032-1037.
  13. Lobov, I.B. et al. (2007) Proc. Natl. Acad. Sci. USA 104, 3219-3224.
  14. Scehnet, J.S. et al. (2007) Blood 109, 4753-4760.

Application References

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Companion Products

This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.

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