title: Genome-wide identification of phospho-regulators of Wnt signaling in Drosophila.
abstract: Evolutionarily conserved intercellular signaling pathways regulate embryonic development and adult tissue homeostasis in metazoans. The precise control of the state and amplitude of signaling pathways is achieved in part through the kinase- and phosphatase-mediated reversible phosphorylation of proteins. In this study, we performed a genome-wide in vivo RNAi screen for kinases and phosphatases that regulate the Wnt pathway under physiological conditions in the Drosophila wing disc. Our analyses have identified 54 high-confidence kinases and phosphatases capable of modulating the Wnt pathway, including 22 novel regulators. These candidates were also assayed for a role in the Notch pathway, and numerous phospho-regulators were identified. Additionally, each regulator of the Wnt pathway was evaluated in the wing disc for its ability to affect the mechanistically similar Hedgehog pathway. We identified 29 dual regulators that have the same effect on the Wnt and Hedgehog pathways. As proof of principle, we established that Cdc37 and Gilgamesh/CK1γ inhibit and promote signaling, respectively, by functioning at analogous levels of these pathways in both Drosophila and mammalian cells. The Wnt and Hedgehog pathways function in tandem in multiple developmental contexts, and the identification of several shared phospho-regulators serve as potential nodes of control under conditions of aberrant signaling and disease.
authors: Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby V5A1S6, British Columbia, Canada.
authors: Sharan
authors: S
authors: Swarup
authors: Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby V5A1S6, British Columbia, Canada.
authors: Tirthadipa
authors: T
authors: Pradhan-Sundd
authors: Simon Fraser University, Department of Molecular Biology and Biochemistry, Burnaby V5A1S6, British Columbia, Canada everheye@sfu.ca.
authors: Esther M
authors: EM
authors: Verheyen
mesh_terms: D000818:Animals; D047389:Casein Kinase I / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000072086:Smoothened Receptor; D014921:Wings, Animal / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C088085:Cdc37 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D018832:Molecular Chaperones; C497759:N protein, Drosophila; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D000072086:Smoothened Receptor; D051153:Wnt Proteins; D051155:Wnt1 Protein; C100664:smo protein, Drosophila; C074622:wg protein, Drosophila; C077245:hh protein, Drosophila; D047389:Casein Kinase I; C479663:gish protein, Drosophila
keywords: Hedgehog; In vivo RNAi screen; Notch; Wingless; Wnt