Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling

Nat Rev Mol Cell Biol. 2002 Sep;3(9):673-84. doi: 10.1038/nrm910.


Many cell-surface receptors transmit signals to the nucleus through complex protein cascades. By contrast, the Notch signalling pathway uses a relatively direct mechanism, in which the intracellular domain of the receptor is liberated by intramembrane cleavage and translocates to the nucleus. This critical cleavage is mediated by the gamma-secretase complex, and new findings reveal that this mechanism is used by various receptors, although many questions remain about the biochemical details.

Publication types

  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Animals
  • Aspartic Acid Endopeptidases
  • Cell Membrane / enzymology
  • Endopeptidases / chemistry
  • Endopeptidases / metabolism*
  • Humans
  • Macromolecular Substances
  • Membrane Proteins / metabolism*
  • Protein Processing, Post-Translational*
  • Protein Transport
  • Receptors, Cell Surface / metabolism*
  • Receptors, Notch
  • Signal Transduction*


  • Macromolecular Substances
  • Membrane Proteins
  • Receptors, Cell Surface
  • Receptors, Notch
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human