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Signal Transduction
Metazoans
Notch Signaling Pathway
Juxtacrine signaling controlling cell fate decisions via proteolytic receptor activation.
Overview
Notch signaling is activated when transmembrane ligands (Delta/Jagged) on one cell bind Notch receptors on an adjacent cell. This triggers sequential proteolytic cleavage by ADAM metalloproteases and γ-secretase, releasing the Notch Intracellular Domain (NICD). NICD translocates to the nucleus and forms a complex with CSL/RBP-Jκ to activate transcription of target genes (HES, HEY families).
Cellular Location
Membrane → Nucleus
Clinical Significance
Master regulator of cell fate in development; T-cell acute lymphoblastic leukemia often involves activating NOTCH1 mutations.