Protein O-GlcNAcylation is required for fibroblast growth factor signaling in Drosophila
| Autor: | Daniel Mariappa, H.-Arno J. Müller, Karina Mariño, Michael A. J. Ferguson, Ryan Webster, Kathrin Sauert, Daniel C. Turnock, Daan M. F. van Aalten |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Receptor complex
Glucosamine Glycosylation Fibroblast growth factor receptor 2 Medizin Cell Biology Fibroblast growth factor receptor 4 Fibroblast growth factor receptor 3 Biology Fibroblast growth factor Biochemistry Molecular biology Receptors Fibroblast Growth Factor Article Fibroblast Growth Factors Drosophila melanogaster Epidermal growth factor Fibroblast growth factor receptor Phosphotransferases (Phosphomutases) Mutation Animals Drosophila Proteins Signal transduction Molecular Biology Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|