RRC ID 33721
Author Swarup S, Pradhan-Sundd T, Verheyen EM.
Title Genome-wide identification of phospho-regulators of Wnt signaling in Drosophila.
Journal Development
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.
Volume 142(8)
Pages 1502-15
Published 2015-4-15
DOI 10.1242/dev.116715
PII 142/8/1502
PMID 25852200
MeSH Animals Casein Kinase I / genetics Casein Kinase I / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Hedgehog Proteins / genetics Hedgehog Proteins / metabolism Molecular Chaperones / genetics Molecular Chaperones / metabolism Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism Receptors, Notch / genetics Receptors, Notch / metabolism Smoothened Receptor Wings, Animal / metabolism Wnt Proteins / genetics Wnt Proteins / metabolism* Wnt1 Protein / genetics Wnt1 Protein / metabolism
IF 5.413
Times Cited 5
WOS Category DEVELOPMENTAL BIOLOGY
Resource
Drosophila 10033R-1 10033R-2 10079R-2 10268R-2 10498R-2 10579R-3 10738R-1 10776R-2 10967R-1 11420R-3 11486R-3 11486R-4 12072R-1 12306R-2 12306R-3 13369R-1 14030R-1 14030R-2 14305R-3 14992R-1 1609R-2 1609R-4 16973R-2 17010R-2 17010R-3 17090R-1 17245R-2 1725R-2 1725R-1 17299R-1 17299R-3 1747R-3 17520R-2 18255R-1 18255R-3 18374R-3 1388R-2 1851R-2 2048R-1 2048R-3 2055R-2 2210R-2 2210R-1 2252R-2 2272R-1 2621R-3 2621R-1 31643R-1 31643R-2 2905R-3 1630R-2 2829R-1 3608R-2 4551R-1 4551R-3 5092R-1 5092R-2 5373R-25626R-1 6117R-1 6117R-2 6214R-3 6292R-3 6297R-4 6620R-3 6767R-1 7328R-1 7393R-3 7524R-3 7551R-1 7551R-3 7643R-3 7719R-1 7838R-1 7904R-2 7904R-3 8057R-4 8298R-3 8565R-2 8657R-2 8967R-2 9746R-1 11438R-3 11438R-2 12034R-1 1395R-1 1395R-2 14211R-4 14297R-4 15400R-2 16771R-2 16870R-2 16870R-1 17124R-3 1809R-1 15305R-1 2984R-4 2984R-3 31717R-1 31717R-3 2077R-1 3101R-1 3292R-2 5171R-3 5177R-1 5177R-2 5577R-1 5643R-3 5830R-2 5851R-1 6235R-2 6542R-1 6542R-2 6562R-1 6562R-2 6571R-2 6896R-1 7134R-6 7942R-4 8402R-1 8455R-2 8509R-2 8805R-1 8889R-2 9115R-1 9115R-2 9156R-1 9311R-3 9493R-3 9493R-2 9856R-1 9856R-2