Protein O-GlcNAcylation is required for Fibroblast Growth Factor signaling in Drosophila

MARIAPPA, DANIEL; SAUERT, KATHRIN; MARIÑO, KARINA; TURNOCK, DANIEL; WEBSTER, RYAN; VAN AALTEN, DAAN M.F.; FERGUSON, M.A.J; MULLER, HANS ARNO J.

SCIENCE SIGNALING

AMER ASSOC ADVANCEMENT SCIENCE

Año: 2011 vol. 4 p. 1 - 8

1937-9145

Glycosylation is essential for growth factor signalling through Nglycosylationof ligands and receptors and the biosynthesis ofproteoglycans as co-receptors. Here, we show that nucleo-cytoplasmicprotein O-GlcNAcylation is crucial for Fibroblast Growth factor (FGF)signaling in Drosophila. Low levels of intracellular UDP-Nacetylglucosamine(UDP-GlcNAc) in nesthocker (nst) mutants disruptprotein O-GlcNAcylation. Nst (phosphoacetylglucosamine mutase) isrequired for FGF-dependent, but not Epidermal Growth FactordependentMAP kinase activation. We show that nst is dispensable forthe function of the FGF ligands and the FGF receptor’s extracellulardomain, but that Nst is essential in the signal receiving cellsdownstream of the FGF receptor. We identify the adaptor protein Dofas target for O-GlcNAcylation in the FGF pathway suggesting thatprotein O-GlcNAcylation of the activated receptor complex is essentialfor FGF signal transduction.