Title | Evaluating Smoothened as a G-protein-coupled receptor for Hedgehog signalling. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Ayers KL, Thérond PP |
Journal | Trends in cell biology |
Volume | 20 |
Issue | 5 |
Pagination | 287-98 |
Date Published | 2010 May |
ISSN | 1879-3088 |
Keywords | Animals, Drosophila Proteins, Hedgehog Proteins, Humans, Models, Biological, Phosphorylation, Protein Binding, Receptors, G-Protein-Coupled, Signal Transduction |
Abstract | 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. |
DOI | 10.1016/j.tcb.2010.02.002 |
Alternate Journal | Trends Cell Biol. |