Xenbase Image ID: 139912

Fig. 2. NOTCH signaling pathway. In the golgi apparatus the Notch receptor undergoes proteolytic processing, which is S1 cleavage mediated by Furin proteases. The receptor is transported to the cell surface membrane. The extracellular domain of the Notch receptor (Notch-ECD) in the signalling cell binds with the Notch ligands (Delta, Jagged, Serrate) expressed by the adjacent cell. This induces the second proteolytic step, S2 cleavage by ADAM metalloproteases, and leads to the endocytosis of the Notch-ECD into the ligand-expressing cell. This is followed by the release of the Notch intracellular domain (Notch-ICD) with a tethered membrane. This is now a substrate for the gamma secretase enzyme complex, which cleaves the Notch-ICD from the membrane by S3 and S4 cleavages. The resulting active Notch-ICD translocates to the nucleus and interacts with the CSL protein. In the absence of Notch-ICD, the CSL is bound to co-repressor. Binding of Notch-ICD with CSL results in the formation of an active complex with MAML and other co-activators and leads to the transcription of Notch targets HES and HEY Image published in: Suresh S and Irvine AE (2015) Image downloaded from an Open Access article in PubMed Central. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Larger Image Printer Friendly View

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