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NOTCH2 Activation and Transmission of Signal to the Nucleus
Summary
- Organism
- Homo sapiens (human)
- Reactome
- R-HSA-2979096
- PubChem
- R-HSA-2979096
- Description
-
- Similar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). The activation triggers cleavage of NOTCH2, first by ADAM10 at the S2 cleavage site (Gibb et al. 2010, Shimizu et al. 2000), then by gamma-secretase at the S3 cleavage site (Saxena et al. 2001, De Strooper et al. 1999), resulting in the release of the intracellular domain of NOTCH2, NICD2, into the cytosol. NICD2 subsequently traffics to the nucleus where it acts as a transcription regulator.
While DLL and JAG ligands are well established, canonical NOTCH2 ligands, there is limited evidence that NOTCH2, similar to NOTCH1, can be activated by CNTN1 (contactin 1), a protein involved in oligodendrocyte maturation (Hu et al. 2003). MDK (midkine), which plays an important role in epithelial to mesenchymal transition, can also activate NOTCH2 signaling and is able to bind to the extracellular domain of NOTCH2, but the exact mechanism of MDK-induced NOTCH2 activation has not been elucidated (Huang et al. 2008, Gungor et al. 2011).
- Similar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). The activation triggers cleavage of NOTCH2, first by ADAM10 at the S2 cleavage site (Gibb et al. 2010, Shimizu et al. 2000), then by gamma-secretase at the S3 cleavage site (Saxena et al. 2001, De Strooper et al. 1999), resulting in the release of the intracellular domain of NOTCH2, NICD2, into the cytosol. NICD2 subsequently traffics to the nucleus where it acts as a transcription regulator.
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
| UniProt ID | Protein Name | Gene Symbol | Pathway Viewer |
|---|---|---|---|
| O00548 | Delta-like protein 1 |
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| O14672 | Disintegrin and metalloproteinase domain-containing protein 10 |
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| P0DPK3 | Notch homolog 2 N-terminal-like protein B |
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| P0DPK4 | Notch homolog 2 N-terminal-like protein C |
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| P21741 | Midkine |
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| P62979 | Ubiquitin-ribosomal protein eS31 fusion protein |
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| P62987 | Ubiquitin-ribosomal protein eL40 fusion protein |
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| P78504 | Protein jagged-1 |
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| Q04721 | Neurogenic locus notch homolog protein 2 |
|
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| Q12860 | Contactin-1 |
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