title: Protein O-GlcNAcylation is required for fibroblast growth factor signaling in Drosophila.
abstract: Glycosylation is essential for growth factor signaling through N-glycosylation of ligands and receptors and the biosynthesis of proteoglycans as co-receptors. Here, we show that protein O-GlcNAcylation is crucial for fibroblast growth factor (FGF) signaling in Drosophila. We found that nesthocker (nst) encodes a phosphoacetylglucosamine mutase and that nst mutant embryos exhibited low amounts of intracellular uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc), which disrupted protein O-GlcNAcylation. Nst was required for mitogen-activated protein kinase (MAPK) signaling downstream of FGF but not MAPK signaling activated by epidermal growth factor. nst was dispensable for the function of the FGF ligands and the FGF receptor's extracellular domain but was essential in the signal-receiving cells downstream of the FGF receptor. We identified the adaptor protein Downstream of FGF receptor (Dof), which interacts with the FGF receptor, as the relevant target for O-GlcNAcylation in the FGF pathway, suggesting that protein O-GlcNAcylation of the activated receptor complex is essential for FGF signal transduction.
authors.affiliation: Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mariappa
authors.forename: Kathrin
authors.initials: K
authors.lastname: Sauert
authors.forename: Karina
authors.initials: K
authors.lastname: Mariño
authors.forename: Daniel
authors.initials: D
authors.lastname: Turnock
authors.forename: Ryan
authors.initials: R
authors.lastname: Webster
authors.forename: Daan M F
authors.initials: DM
authors.lastname: van Aalten
authors.forename: Michael A J
authors.initials: MA
authors.lastname: Ferguson
authors.forename: H-Arno J
authors.initials: HA
authors.lastname: Müller
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D009154:Mutation; D017875:Phosphotransferases (Phosphomutases) / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D017468:Receptors, Fibroblast Growth Factor; C115576:stumps protein, Drosophila; C026712:UDP-glucosamine; D005346:Fibroblast Growth Factors; D017875:Phosphotransferases (Phosphomutases); C018718:phosphoacetylglucosamine mutase; D005944:Glucosamine