Ectodomain shedding of the EGF-receptor ligand epigen is mediated by ADAM17

FEBS Lett. 2007 Jan 9;581(1):41-4. doi: 10.1016/j.febslet.2006.11.074. Epub 2006 Dec 6.

Abstract

All ligands of the epidermal growth factor receptor (EGFR), which has important roles in development and disease, are made as transmembrane precursors. Proteolytic processing by ADAMs (a disintegrin and metalloprotease) regulates the bioavailability of several EGFR-ligands, yet little is known about the enzyme responsible for processing the recently identified EGFR ligand, epigen. Here we show that ectodomain shedding of epigen requires ADAM17, which can be stimulated by phorbol esters, phosphatase inhibitors and calcium influx. These results suggest that ADAM17 might be a good target to block the release of bioactive epigen, a highly mitogenic ligand of the EGFR which has been implicated in wound healing and cancer.

Publication types

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

MeSH terms

  • ADAM Proteins / antagonists & inhibitors
  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • ADAM17 Protein
  • Animals
  • Cells, Cultured
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Epigen
  • ErbB Receptors / agonists
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / enzymology*
  • Growth Substances / genetics
  • Growth Substances / metabolism*
  • Humans
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protease Inhibitors / pharmacology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology
  • Protein Structure, Tertiary / genetics
  • Wound Healing / drug effects
  • Wound Healing / genetics

Substances

  • EPGN protein, human
  • Epgn protein, mouse
  • Epigen
  • Growth Substances
  • Ligands
  • Membrane Proteins
  • Protease Inhibitors
  • Protein Precursors
  • Epidermal Growth Factor
  • ErbB Receptors
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human
  • Adam17 protein, mouse