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Published on: September 20, 2011
A G protein-coupled receptor for UDP-glucose
J K Chambers1, L E Macdonald, H M Sarau
1Department of Vascular Biology, New Frontiers Science Park, SmithKline Beecham Pharmaceuticals, Southern Way, Harlow, Essex CM19 5AW, United Kingdom. Jon_Chambers-1@sbphrd.com
The Journal of Biological Chemistry
|February 7, 2001
Summary
Uridine 5'-diphosphoglucose (UDP-glucose) activates a novel G protein-coupled receptor, KIAA0001. This finding suggests sugar-nucleotides may function as extracellular signaling molecules in various human tissues, including the brain.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Uridine 5 '-diphosphoglucose (UDP-glucose) is primarily known as a precursor in carbohydrate biosynthesis.
- Emerging evidence suggests UDP-glucose may have uncharacterized pharmacological activities.
- The existence of a potential receptor for UDP-glucose was hypothesized.
Purpose of the Study:
- To identify and characterize the receptor for UDP-glucose.
- To investigate the pharmacological properties of UDP-glucose and related molecules.
- To determine the tissue distribution of the identified receptor.
Main Methods:
- Heterologous expression of the orphan G protein-coupled receptor KIAA0001 in yeast and mammalian cells.
- Ligand-binding and activation assays using UDP-glucose and related compounds.
- Pharmacological profiling by testing known P2Y receptor agonists.
- Quantitative analysis of receptor expression in various human tissues.
Main Results:
- UDP-glucose and certain related molecules were found to be potent activators of KIAA0001.
- Known P2Y receptor agonists did not activate KIAA0001, highlighting novel receptor pharmacology.
- KIAA0001 expression was detected across a broad range of human tissues, including the brain.
Conclusions:
- The orphan G protein-coupled receptor KIAA0001 is activated by UDP-glucose, identifying it as a potential UDP-glucose receptor.
- This discovery reveals a novel class of extracellular signaling molecules and their receptors.
- The widespread expression suggests significant physiological roles for sugar-nucleotides beyond intermediary metabolism.
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