The Notch signaling pathway plays a vital role in the regulation of asymmetric cell division, cell fate specification and proliferation. Mammals possess 4 different Notch receptors, referred to as Notch1, 2, 3, and 4. The Notch receptor is a hetero-oligomer transmembrane protein that comprises a large extracellular domain, a single-pass transmembrane span, and a small intracellular region.
The ligands for Notch receptors, DSL (Delta (referred to Delta-like family in mammals), Serrate (referred to as Jagged family in mammals) and Lag-2), are also transmembrane proteins, indicating the signaling is triggered upon physical contact between two individual cells. This direct cell-to-cell contact is a key characteristic to the Notch pathway, in which lateral inhibition is elicited from a signal-sending cell to its neighbor signal-receiving cells.
Proper maturation of the Notch receptor requires specific glycosylation by POFUT1 and Fringe (referred to MFNG, LFNG, and RFNG in mammals), along with proteolytic cleavage by FURIN at the prospective extracellular region of the pre-Notch protein during its intracellular trafficking through Golgi complex. This results in a bipartite-protein receptor that ultimately anchors on cell surface.
Binding of ligand to the Notch receptor initiates two independent proteolytic cleavages. First, the metalloprotease ADAM family cleaves the Notch extracellular domain. This domain remains bound to the ligand and is endocytosed by the signal-sending cell. Next, the y-secretase complex (PSEN1/2, APH1, PEN2 and NCSTN) cleaves Notch at its intracellular site and releases the Notch intracellular domain (NICD) within the signal-receiving cell. NICD then translocates into the nucleus, where it regulates gene expression by activating the transcription factor CSL.
A selection of 100% guaranteed research antibodies related to the Notch pathway
- RBP-Jkappa : rabbit polyclonal antibody to RBP-Jkappa, a recombination signal binding protein for immunoglobulin kappa J region
- GSK3 : rabbit polyclonal antibody to GSK3 beta a glycogen synthase kinase 3 beta
- Anti Notch 2 [C2], C-term : rabbit polyclonal antibody to NOTCH2, a Notch homolog 2 (Drosophila)
- Anti ADAM10: rabbit polyclonal for detection and localization of human ADAM10
- Anti ADAM17/ TACE, C-Term: goat polyclonal antibody specific for ADAM17/TACE
- Anti CDK8: Rabbit polyclonal antibody to Cdk8
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