title: Smoothened Regulation: A Tale of Two Signals.
abstract: The G protein-coupled receptor (GPCR) Smoothened (Smo) is the signal transducer of the developmentally and therapeutically relevant Hedgehog (Hh) pathway. Although recent structural analyses have advanced our understanding of Smo biology, several questions remain. Chief among them are the identity of its natural ligand, the regulatory processes controlling its activation, and the mechanisms by which it signals to downstream effectors. In this review, we discuss recent discoveries from multiple model systems that have set the stage for solving these mysteries. We focus on the roles of distinct Smo functional domains, post-translational modifications, and trafficking, and conclude by discussing their contributions to signal output.
authors.affiliation: Department of Cell and Molecular Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place MS#340, Memphis, TN 38105, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Arensdorf
authors.affiliation: Department of Cell and Molecular Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place MS#340, Memphis, TN 38105, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Marada
authors.affiliation: Department of Cell and Molecular Biology, St Jude Children's Research Hospital, 262 Danny Thomas Place MS#340, Memphis, TN 38105, USA. Electronic address: Stacey.Ogden@stjude.org.
authors.forename: Stacey K
authors.initials: SK
authors.lastname: Ogden
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D000072086:Smoothened Receptor
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; C100664:smo protein, Drosophila
keywords: GPCR; Hedgehog; Smoothened; canonical signaling; noncanonical signaling