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J Biol Chem. 2006 Mar 17;281(11):7237-43. Epub 2006 Jan 19.

Smoothened regulates activator and repressor functions of Hedgehog signaling via two distinct mechanisms.

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  • 1Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA.

Abstract

The secreted protein Hedgehog (Hh) plays an important role in metazoan development and as a survival factor for many human tumors. In both cases, Hh signaling proceeds through the activation of the seven-transmembrane protein Smoothened (Smo), which is thought to convert the Gli family of transcription factors from transcriptional repressors to transcriptional activators. Here, we provide evidence that Smo signals to the Hh signaling complex, which consists of the kinesin-related protein Costal2 (Cos2), the protein kinase Fused (Fu), and the Drosophila Gli homolog cubitus interruptus (Ci), in two distinct manners. We show that many of the commonly observed molecular events following Hh signaling are not transmitted in a linear fashion but instead are activated through two signals that bifurcate at Smo to independently affect activator and repressor pools of Ci.

PMID:
16423832
[PubMed - indexed for MEDLINE]
PMCID:
PMC3677211
Free PMC Article

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