title: Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila.
abstract: Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accumulation in Drosophila wings. Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolateral accumulation and attenuates Hh target gene expression. In contrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promotes Hh signaling. The aPKC-mediated phosphorylation of Smo at Ser680 promotes Ser683 phosphorylation by casein kinase 1 (CK1), and these phosphorylation events elevate Smo activity in vivo. Moreover, aPKC has an additional positive role in Hh signaling by regulating the activity of Cubitus interruptus (Ci) through phosphorylation of the Zn finger DNA-binding domain. Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent manner. Our findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity.
authors.affiliation: Markey Cancer Center and.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Markey Cancer Center and.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Markey Cancer Center and.
authors.forename: Junkai
authors.initials: J
authors.lastname: Fan
authors.affiliation: Markey Cancer Center and.
authors.forename: Garretson
authors.initials: G
authors.lastname: Epperly
authors.affiliation: Markey Cancer Center and Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536-0509; and.
authors.forename: Tianyan
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Markey Cancer Center and Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536-0509; and jianhang.jia@uky.edu.
authors.forename: Jianhang
authors.initials: J
authors.lastname: Jia
mesh_terms: D000818:Animals; D047389:Casein Kinase I / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D014921:Wings, Animal / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014157:Transcription Factors; C092937:ci protein, Drosophila; C100664:smo protein, Drosophila; C077245:hh protein, Drosophila; D047389:Casein Kinase I; C115015:PKC-3 protein; D011493:Protein Kinase C
keywords: Ci; Hh; Par6; Smo; aPKC