| http://purl.uniprot.org/citations/19850026 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19850026 | http://www.w3.org/2000/01/rdf-schema#comment | "The Hedgehog (Hh) signaling pathway plays a conserved and essential role in regulating development and homeostasis of numerous tissues. Cytoplasmic signaling is initiated by Smoothened (Smo), a G-protein-coupled receptor (GPCR) family member, whose levels and activity are regulated by the Hh receptor Patched (Ptc). In response to Hh binding to Ptc, Ptc-mediated repression of Smo is relieved, leading to Smo activation, surface accumulation, and downstream signaling. We find that downregulation of Drosophila Smo protein in Hh-responding imaginal disc cells is dependent on the activity of G-protein-coupled receptor kinase 2 (Gprk2). By analyzing gain- and null loss-of-function phenotypes, we provide evidence that Gprk2 promotes Smo internalization subsequent to its activation, most likely by direct phosphorylation. Ptc-dependent regulation of Smo accumulation is normal in gprk2 mutants, indicating that Gprk2 and Ptc downregulate Smo by different mechanisms. Finally, we show that both Drosophila G-protein-coupled receptor kinase orthologues, Gprk1 and Gprk2, act in a partially redundant manner to promote Hh signaling. Our results suggest that Smo is regulated by distinct Ptc-dependent and Gprk2-dependent trafficking mechanisms in vivo, analogous to constitutive and activity-dependent regulation of GPCRs. G-protein-coupled receptor kinase activity is also important for efficient downstream signaling."xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ydbio.2009.10.014"xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/author | "Cheng S."xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/author | "Maier D."xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/author | "Hipfner D.R."xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/author | "Neubueser D."xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/name | "Dev Biol"xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/pages | "99-109"xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/title | "Regulation of smoothened by Drosophila G-protein-coupled receptor kinases."xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://purl.uniprot.org/core/volume | "337"xsd:string |
| http://purl.uniprot.org/citations/19850026 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19850026 |
| http://purl.uniprot.org/citations/19850026 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19850026 |
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