The full-length unprocessed hedgehog protein is an active signaling molecule Academic Article uri icon


MeSH Major

  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Signal Transduction


  • The hedgehog (HH) family of ligands plays an important instructional role in metazoan development. HH proteins are initially produced as approximately 45-kDa full-length proteins, which undergo an intramolecular cleavage to generate an amino-terminal product that subsequently becomes cholesterol-modified (HH-Np). It is well accepted that this cholesterol-modified amino-terminal cleavage product is responsible for all HH-dependent signaling events. Contrary to this model we show here that full-length forms of HH proteins are able to traffic to the plasma membrane and participate directly in cell-cell signaling, both in vitro and in vivo. We were also able to rescue a Drosophila eye-specific hh loss of function phenotype by expressing a full-length form of hh that cannot be processed into HH-Np. These results suggest that in some physiological contexts full-length HH proteins may participate directly in HH signaling and that this novel activity of full-length HH may be evolutionarily conserved.

publication date

  • January 22, 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2807313

Digital Object Identifier (DOI)

  • 10.1074/jbc.M109.078626

PubMed ID

  • 19920144

Additional Document Info

start page

  • 2562

end page

  • 8


  • 285


  • 4