Notch is synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase (S1 cleavage) in the trans-golgi network before it reaches the plasma membrane to yield an active, ligand- accessible form.
Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC).
Following ligand binding, it is cleaved (S2 cleavage) by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called Notch extracellular truncation (NEXT).
This fragment is then cleaved by presenilin-dependent gamma- secretase (S3 cleavage) to release the intracellular domain (NICD) from the membrane.
Notch functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination.
Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBP-J kappa and activates genes of the enhancer of split locus.
Affects the implementation of differentiation, proliferation and apoptotic programs.
Applications:Suitable for use in ELISA, Immunohistochemistry and Western Blot.
Other applications not tested.
Recommended Dilution:ELISA: 1:15,000-1:45,000Western Blot: 1:200-1:1000, Detects a band at~110kDImmunohistochemistry (FFPE): 1:250Optimal dilutions to be determined by the researcher.
