The importance of shedding of membrane proteins for cytokine biology

Eur Cytokine Netw. 2000 Mar;11(1):27-38.


Most transmembrane proteins are subjected to limited proteolysis by cellular proteases. The recent molecular cloning of the TNF-a converting enzyme (TACE) revealed that this shedding enzyme belongs to a family of metalloproteinases which contain a disintegrin domain (ADAM family). The activity of these proteases seems to be tightly regulated. Mice lacking functional TACE are not viable demonstrating the importance of this enzyme for body homeostasis. This review describes the current knowledge of shedding enzymes, the ADAM protein family, the mechanism of shedding as well as physiological consequences of shedding of cytokines and cytokine receptors for cytokine biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADAM Proteins
  • ADAM17 Protein
  • Animals
  • Cytokines / physiology*
  • Homeostasis
  • Humans
  • Membrane Proteins / physiology*
  • Metalloendopeptidases / deficiency
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Knockout
  • Receptors, Cytokine / physiology
  • Tumor Necrosis Factor-alpha / physiology*


  • Cytokines
  • Membrane Proteins
  • Receptors, Cytokine
  • Tumor Necrosis Factor-alpha
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAM17 Protein
  • ADAM17 protein, human
  • Adam17 protein, mouse