An essential role for ectodomain shedding in mammalian development

Science. 1998 Nov 13;282(5392):1281-4. doi: 10.1126/science.282.5392.1281.


The ectodomains of numerous proteins are released from cells by proteolysis to yield soluble intercellular regulators. The responsible protease, tumor necrosis factor-alpha converting enzyme (TACE), has been identified only in the case when tumor necrosis factor-alpha (TNFalpha) is released. Analyses of cells lacking this metalloproteinase-disintegrin revealed an expanded role for TACE in the processing of other cell surface proteins, including a TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (TGFalpha). The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo.

Publication types

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

MeSH terms

  • ADAM Proteins
  • ADAM17 Protein
  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Crosses, Genetic
  • Embryonic and Fetal Development*
  • L-Selectin / metabolism
  • Ligands
  • Membrane Proteins / metabolism*
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Protein Processing, Post-Translational
  • Receptors, Tumor Necrosis Factor / metabolism
  • Transforming Growth Factor alpha / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*


  • Ligands
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Transforming Growth Factor alpha
  • Tumor Necrosis Factor-alpha
  • L-Selectin
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAM17 Protein
  • Adam17 protein, mouse