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(https://www.bocsci.com/notch-signaling-pathway.html)

Cross-talk between Notch and other signaling pathways

The Notch signaling pathway regulates cellular identity, proliferation, differentiation and apoptosis by means of cell–cell interactions. It also plays a crucial role in a wide array of developmental processes, including the regulation of neurogenesis, myogenesis, angiogenesis, hematopoiesis and epithelial to mesenchymal transition, and tissue homeostasis. Notch signaling has recently been shown to interact with several of the other key signaling mechanisms. Notch displays functional interactions with other signaling pathways in sequential cell fate assignations, such as Wnt signaling. And Notch interacts with the Ras/MAP kinase signaling pathway, although the outcome of this interaction appears to vary depending on the cellular context. Ras activates Notch in Ras-transformed human cultured cells, and Notch is required to maintain a neoplastic phenotype caused by Ras signaling. Interplay between Notch and TGF-β / BMP signaling has been identified. It was observed that the cell cycle-inhibitory effects of TGF-β in cultured cells could be overridden by Notch ICD. A direct interaction between Notch ICD and SMAD3 (intracellular transducer of TGF- β signaling) was demonstrated where activation of TGF-β leads to an increase in expression of the Hes1 gene. Similar cross-talk occurs also between Notch and BMP.