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)

external resources
NCBI:1269539
REACTOME:R-HSA-2979096
PUBMED:14567914
PUBMED:11518718
PUBMED:10934472
PUBMED:10206645
PUBMED:15569487
PUBMED:10551863
PUBMED:21632553
PUBMED:10958687
PUBMED:20156974
PUBMED:18469519

genes
ADAM10 , JAG1 , CNTN1 , JAG2 , MDK , NOTCH2 , PSEN2 , RPS27A , UBA52 , UBB , UBC , NEURL1 , NCSTN , DLL1 , APH1A , NEURL1B , DLL4 , PSENEN , MIB1 , APH1B , MIB2 ,