title: Smoothened regulation in response to Hedgehog stimulation.
abstract: The Hedgehog (Hh) signaling pathway play critical roles in embryonic development and adult tissue homeostasis. A critical step in Hh signal transduction is how Hh receptor Patched (Ptc) inhibits the atypical G protein-coupled receptor Smoothened (Smo) in the absence of Hh and how this inhibition is release by Hh stimulation. It is unlikely that Ptc inhibits Smo by direct interaction. Here we discuss how Hh regulates the phosphorylation and ubiquitination of Smo, leading to cell surface and ciliary accumulation of Smo inDrosophilaand vertebrate cells, respectively. In addition, we discuss how PI(4)P phospholipid acts in between Ptc and Smo to regulate Smo phosphorylation and activation in response to Hh stimulation.
authors.affiliation: Markey Cancer Center, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Markey Cancer Center, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
authors.forename: Jianhang
authors.initials: J
authors.lastname: Jia
keywords: Hh signaling; Smo; phospholipid; phosphorylation; signal transduction; ubiquitination