ADAM proteases: ligand processing and modulation of the Notch pathway

Cell Mol Life Sci. 2008 Jul;65(13):2056-68. doi: 10.1007/s00018-008-7586-4.


ADAM metalloproteases play important roles in development and disease. One of the key functions of ADAMs is the proteolytic processing of Notch receptors and their ligands. ADAM-mediated cleavage of Notch represents the first step in regulated intramembrane proteolysis of the receptor, leading to activation of the Notch pathway. Recent reports indicate that the transmembrane Notch ligands also undergo ADAM-mediated processing in cultured cells and in vivo. The proteolytic processing of Notch ligands modulates the strength and duration of Notch signals, leads to generation of soluble intracellular domains of the ligands, and may support a bi-directional signaling between cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • Amino Acid Sequence
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Protein Processing, Post-Translational
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • Ligands
  • Receptors, Notch
  • Amyloid Precursor Protein Secretases
  • ADAM Proteins