Wnt / Hedgehog / Notch

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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).

Mutation in Jagged1 is associated with Alagille syndrome, an autosomal dominant disorder characterized by abnormal development of liver, heart, skeleton, eye, and face (7, 8) and Tetralogy of Fallot (ToF), a common form of complex congenital heart disease (9). Jagged1 expression is associated with prostate cancer metastasis and recurrence (10).

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. Li, L. et al. (1997) Nat. Genet. 16, 243-251.
8. Röpke, A. et al. (2003) Hum. Mutat. 21, 100.
9. Eldadah, Z.A. et al. (2001) Hum. Mol. Genet. 10, 163-169.
10. Santagata, S. et al. (2004) Cancer Res. 64, 6854-6857.

• Ghosh, S. et al. (2011) J Biol Chem 286, 22678-87. Applications: Western Blotting

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Jagged1 (1C4) Rabbit mAb

©1999-2012 Cell Signaling Technology, Inc.

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Jagged1 (1C4) Rabbit mAbのCSTジャパン