Hedgehog patterning activity: role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain

Cell. 1996 Jul 12;86(1):21-34. doi: 10.1016/s0092-8674(00)80074-4.


Autocatalytic processing mediated by the carboxyterminal domain of the hedgehog (hh) protein precursor (Hh) generates an amino-terminal product that accounts for all known signaling activity. The role of autoprocessing biogenesis of the hh signal has been unclear, since a truncated unprocessed protein lacking all carboxy-terminal domain sequences retains signaling activity. Here, we present evidence that the autoprocessing reaction proceeds via an internal thioester intermediate and results in a covalent modification that increases the hydrophobic character of the signaling domain and influences its spatial and subcellular distribution. We demonstrate that truncated unprocessed amino-terminal protein causes embryonic mispatterning, even when expression is localized to cells that normally express Hh, thus suggesting a role for autoprocessing in spatial regulation of hh signaling. This type of processing also appears to operate in the biogenesis of other novel secreted proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured / physiology
  • Consensus Sequence
  • Drosophila / embryology*
  • Drosophila Proteins*
  • Esters / chemistry
  • Hedgehog Proteins
  • Lipids / chemistry
  • Mass Spectrometry
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology
  • Sulfhydryl Compounds / chemistry
  • Water / chemistry


  • Drosophila Proteins
  • Esters
  • Hedgehog Proteins
  • Lipids
  • Proteins
  • Sulfhydryl Compounds
  • Water
  • hh protein, Drosophila

Associated data

  • GENBANK/M75796
  • GENBANK/M89293
  • GENBANK/U61235
  • GENBANK/U61236
  • GENBANK/U61237
  • GENBANK/U61288