Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 20 December 2011
Vol. 4, Issue 204, p. ra89
[DOI: 10.1126/scisignal.2002335]

RESEARCH ARTICLES

Protein O-GlcNAcylation Is Required for Fibroblast Growth Factor Signaling in Drosophila

Daniel Mariappa1, Kathrin Sauert2*, Karina Mariño3{dagger}, Daniel Turnock3{ddagger}, Ryan Webster1, Daan M. F. van Aalten4, Michael A. J. Ferguson3, and H.-Arno J. Müller1§

1 Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
2 Institut für Genetik, Heinrich-Heine Universität, 40225 Düsseldorf, Germany.
3 Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
4 Division of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.

* Present address: AG Entwicklungsbiologie, Universitätsklinikum Essen, Institut für Zellbiologie (Tumorforschung), Hufelandstrasse 55, 45122 Essen, Germany.

{dagger} Present address: National Institute for Bioprocessing Research and Training, Dublin-Oxford Glycobiology Laboratory, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.

{ddagger} Present address: Clinical Biochemistry Laboratory, Salford Royal Foundation Hospital, Salford M6 8HD, UK.

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.

§ To whom correspondence should be addressed. E-mail: h.j.muller{at}dundee.ac.uk

Citation: D. Mariappa, K. Sauert, K. Mariño, D. Turnock, R. Webster, D. M. F. van Aalten, M. A. J. Ferguson, H.- A. J. Müller, Protein O-GlcNAcylation Is Required for Fibroblast Growth Factor Signaling in Drosophila. Sci. Signal. 4, ra89 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Sweet Spot in the FGFR Signal Transduction Pathway.
A. S. Ghabrial (2012)
Science Signaling 5, pe1
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882