title: A sweet spot in the FGFR signal transduction pathway.
abstract: The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have revealed that mutations in genes encoding different enzymes of the hexosamine biosynthetic pathway result in reduction of UDP-GlcNAc to different extents, with a consequent disruption of distinct glycosylation pathways and developmental processes. A maternal and zygotic loss-of-function screen has identified mutations in nesthocker (nst), which encodes an enzyme in the hexosamine biosynthetic pathway. Embryos lacking maternal and zygotic nst gene products show defective O-GlcNAcylation of a fibroblast growth factor receptor (FGFR)-specific adaptor protein, which impairs FGFR-dependent migration of mesodermal and tracheal cells.
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ghabrial@mail.med.upenn.edu
authors.forename: Amin S
authors.initials: AS
authors.lastname: Ghabrial
mesh_terms: D000818:Animals; D004330:Drosophila; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006031:Glycosylation; D006595:Hexosamines / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry*
chemical_list: D006595:Hexosamines; D017468:Receptors, Fibroblast Growth Factor; D014537:Uridine Diphosphate N-Acetylglucosamine; D005346:Fibroblast Growth Factors