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Trends Cell Biol. 2010 May;20(5):287-98. doi: 10.1016/j.tcb.2010.02.002. Epub 2010 Mar 5.

Evaluating Smoothened as a G-protein-coupled receptor for Hedgehog signalling.

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Institute of Developmental Biology and Cancer, CNRS UMR6543, Université Nice - Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.


The Hedgehog signalling pathway controls numerous developmental processes. In response to Hedgehog, Smoothened (Smo), a seven-pass transmembrane protein, orchestrates pathway signalling and controls transcription factor activation. In the absence of Hedgehog, the receptor Patched indirectly inhibits Smo in a catalytic manner. Many questions surrounding Smo activation and signalling remain. Recent findings in Drosophila and vertebrate systems have provided strong evidence that Smo acts as a G-protein-coupled receptor. We discuss the role and regulation of Smo and reassess similarities between Smo and G-protein-coupled receptors. We also examine recently identified members of the invertebrate and vertebrate Smo signalling cascades that are typical components of G-protein-coupled receptor pathways. Greater understanding of the mechanisms of Smo activation and its signalling pathways will allow implementation of novel strategies to target disorders related to disruption of Hh signalling.

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