PathwayStep5557 PathwayStep5555 PathwayStep5553 PathwayStep5551 PathwayStep5518 Signaling by NOTCH1 Signaling by NOTCH Authored: Jassal, B, 2004-12-15 13:08:03 GENE ONTOLOGYGO:0007219 NOTCH Signaling Pathway Pubmed10221902 Pubmed10889061 Pubmed11112321 Pubmed14986688 Reactome Database ID Release 43157118 Reactome, http://www.reactome.org ReactomeREACT_299 Reviewed: Joutel, A, 2004-12-15 The Notch Signaling Pathway (NSP) is a highly conserved pathway for cell-cell communication. NSP is involved in the regulation of cellular differentiation, proliferation, and specification. For example, it is utilised by continually renewing adult tissues such as blood, skin, and gut epithelium not only to maintain stem cells in a proliferative, pluripotent, and undifferentiated state but also to direct the cellular progeny to adopt different developmental cell fates. Analogously, it is used during embryonic development to create fine-grained patterns of differentiated cells, notably during neurogenesis where the NSP controls patches such as that of the vertebrate inner ear where individual hair cells are surrounded by supporting cells.<br>This process is known as lateral inhibition: a molecular mechanism whereby individual cells within a field are stochastically selected to adopt particular cell fates and the NSP inhibits their direct neighbours from doing the same. The NSP has been adopted by several other biological systems for binary cell fate choice. In addition, the NSP is also used during vertebrate segmentation to divide the growing embryo into regular blocks called somites which eventually form the vertebrae. The core of this process relies on regular pulses of Notch signaling generated from a molecular oscillator in the presomatic mesoderm.<br>The Notch receptor is synthesized in the rough endoplasmic reticulum as a single polypeptide precursor. Newly synthesized Notch receptor is proteolytically cleaved in the trans-golgi network, creating a heterodimeric mature receptor comprising of non-covalently associated extracellular and transmembrane subunits. This assembly travels to the cell surface ready to interact with specific ligands. Following ligand activation and further proteolytic cleavage, an intracellular domain is released and translocates to the nucleus where it regulates gene expression. Pre-NOTCH Expression and Processing Signaling by NOTCH2 Signaling by NOTCH3 Signaling by NOTCH4