Smoothened

Smoothened is a is_associated_with::protein that in humans is encoded by the SMO is_associated_with::gene. Smoothened is a is_associated_with::G protein-coupled receptor that is a component of the is_associated_with::hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the is_associated_with::teratogen is_associated_with::cyclopamine.

Function
Cellular localization plays an essential role in the function of SMO. Stimulation of the patched receptor by the is_associated_with::sonic hedgehog ligand leads to translocation of SMO to the primary is_associated_with::cilium. Furthermore, SMO that is mutated in the domain required for ciliary localisation cannot contribute to pathway activation. SMO has also been shown to bind the is_associated_with::kinesin motor protein is_associated_with::Costal-2 and play a role in the localization of the Ci (Cubitus interruptus is_associated_with::transcription factor) complex.

SMO can function as an is_associated_with::oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.



Agonists

 * is_associated_with::Smoothened agonist (SAG)
 * is_associated_with::Purmorphamine

Antagonists

 * is_associated_with::Cyclopamine
 * is_associated_with::Itraconazole
 * is_associated_with::Vismodegib (Erivedge), a smoothened receptor inhibitor for the treatment of is_associated_with::basal-cell carcinoma, being investigated for the treatment of other types of cancer