title: A G protein-coupled receptor for UDP-glucose.
abstract: Uridine 5'-diphosphoglucose (UDP-glucose) has a well established biochemical role as a glycosyl donor in the enzymatic biosynthesis of carbohydrates. It is less well known that UDP-glucose may possess pharmacological activity, suggesting that a receptor for this molecule may exist. Here, we show that UDP-glucose, and some closely related molecules, potently activate the orphan G protein-coupled receptor KIAA0001 heterologously expressed in yeast or mammalian cells. Nucleotides known to activate P2Y receptors were inactive, indicating the distinctly novel pharmacology of this receptor. The receptor is expressed in a wide variety of human tissues, including many regions of the brain. These data suggest that some sugar-nucleotides may serve important physiological roles as extracellular signaling molecules in addition to their familiar role in intermediary metabolism.
authors.affiliation: Department of Vascular Biology, New Frontiers Science Park, SmithKline Beecham Pharmaceuticals, Southern Way, Harlow, Essex CM19 5AW, United Kingdom. Jon_Chambers-1@sbphrd.com
authors.forename: J K
authors.initials: JK
authors.lastname: Chambers
authors.forename: L E
authors.initials: LE
authors.lastname: Macdonald
authors.forename: H M
authors.initials: HM
authors.lastname: Sarau
authors.forename: R S
authors.initials: RS
authors.lastname: Ames
authors.forename: K
authors.initials: K
authors.lastname: Freeman
authors.forename: J J
authors.initials: JJ
authors.lastname: Foley
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: M M
authors.initials: MM
authors.lastname: McLaughlin
authors.forename: P
authors.initials: P
authors.lastname: Murdock
authors.forename: L
authors.initials: L
authors.lastname: McMillan
authors.forename: J
authors.initials: J
authors.lastname: Trill
authors.forename: A
authors.initials: A
authors.lastname: Swift
authors.forename: N
authors.initials: N
authors.lastname: Aiyar
authors.forename: P
authors.initials: P
authors.lastname: Taylor
authors.forename: L
authors.initials: L
authors.lastname: Vawter
authors.forename: S
authors.initials: S
authors.lastname: Naheed
authors.forename: P
authors.initials: P
authors.lastname: Szekeres
authors.forename: G
authors.initials: G
authors.lastname: Hervieu
authors.forename: C
authors.initials: C
authors.lastname: Scott
authors.forename: J M
authors.initials: JM
authors.lastname: Watson
authors.forename: A J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: E
authors.initials: E
authors.lastname: Duzic
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: D J
authors.initials: DJ
authors.lastname: Bergsma
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: G P
authors.initials: GP
authors.lastname: Livi
mesh_terms: D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D010802:Phylogeny; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D014532:Uridine Diphosphate Glucose / Q000502:physiology*
chemical_list: D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins; D014532:Uridine Diphosphate Glucose