Notch signaling pathway

The Notch signaling pathway is a cell-to-cell communication system in which membrane-bound ligands activate Notch receptors on neighboring cells. It converts direct cell contact into changes in gene expression and cell fate.

Delta-like ligands: Delta-like proteins are membrane-bound ligands that activate Notch receptors on neighboring cells. They bind Notch across adjacent cell membranes and initiate signaling.
Notch receptor: A Notch receptor is a single-pass transmembrane protein that receives signals from ligands on neighboring cells. Its ligand-binding and cleavage behavior defines the pathway’s central signal-receiving step.
Notch1: Notch1 is a mammalian Notch receptor with roles in development, tissue maintenance, and disease. Its mutations and altered activity connect pathway biology to cancer and congenital disorders.
Wnt signaling pathway: The Wnt signaling pathway is a family of cell-communication systems regulating development, tissue renewal, and cell behavior. Unlike Notch, many Wnt signals can act over distances rather than requiring direct cell contact.
Jagged (protein): Jagged proteins are membrane-bound ligands in the Delta/Serrate/LAG-2 family that activate Notch receptors. They provide an alternative ligand family for triggering Notch between neighboring cells.
Lateral inhibition: Lateral inhibition is a process in which one cell suppresses a similar fate in neighboring cells. Notch signaling commonly implements this local competition during cell differentiation.
T-cell acute lymphoblastic leukemia: T-cell acute lymphoblastic leukemia is an aggressive cancer of immature T lymphocytes. Activating NOTCH1 mutations drive a substantial fraction of these leukemias.
Hedgehog signaling pathway: The Hedgehog signaling pathway uses secreted proteins to regulate development and tissue patterning. Its diffusible ligands establish spatial signals unlike Notch’s juxtacrine communication.
ADAM metalloprotease: ADAM metalloproteases are membrane-associated enzymes that cleave proteins outside cells or within membrane-proximal regions. After ligand engagement, an ADAM protease performs the first activating cleavage of Notch.
Cell fate determination: Cell fate determination is the process by which cells acquire distinct identities and developmental potentials. Notch regulates gene programs that steer cells toward different developmental identities.

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