Smoothened transduces Hedgehog signal by physically interacting with Costal2/Fused complex through its C-terminal tail

Jianhang Jia, Chao Tong, Jin Jiang

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125 Scopus citations


The Hedgehog (Hh) family of secreted proteins controls many aspects of growth and patterning in animal development. The seven-transmembrane protein Smoothened (Smo) transduces the Hh signal in both vertebrates and invertebrates; however, the mechanism of its action remains unknown. We found that Smo lacking its C-terminal tail (C-tail) is inactive, whereas membrane-tethered Smo C-tail has constitutive albeit low levels of Hh signaling activity. Smo physically interacts with Costal2 (Cos2) and Fused (Fu) through its C-tail. Deletion of the Cos2/Fu-binding domain from Smo abolishes its signaling activity. Moreover, overexpressing Cos2 mutants that fail to bind Fu and Ci but retain Smo-binding activity blocks Hh signaling. Taken together, our results suggest that Smo transduces the Hh signal by physically interacting with the Cos2/Fu protein complex.

Original languageEnglish (US)
Pages (from-to)2709-2720
Number of pages12
JournalGenes and Development
Issue number21
Publication statusPublished - Nov 1 2003



  • Cos2
  • Development
  • Fu
  • Hh
  • Signaling
  • Smo

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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