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RESEARCH PAPER
1 Center for Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA , 2 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA
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.
[Keywords: Smo; Hh; Cos2; Fu; signaling; development]
Received July 23, 2003; revised version accepted September 2, 2003.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1136603.
3 Corresponding author.
E-MAIL jin.jiang{at}utsouthwestern.edu; FAX (214) 648-1960.
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