Glucokinase regulatory protein
1355876
60592881
2006-06-26T02:53:43Z
Arcadian
104523
infobox
{{protein
| Name =
| caption =
| image =
| width =
| HGNCid = 4196
| Symbol = GCKR
| AltSymbols =
| EntrezGene = 2646
| OMIM = 600842
| RefSeq = NM_001486
| UniProt = Q14397
| PDB =
| ECnumber =
| Chromosome = 2
| Arm = p
| Band = 23
| LocusSupplementaryData =
}}
The '''glucokinase regulatory protein''' (GKRP) is a [[protein]] produced in [[hepatocyte]]s ([[liver]] cells) to bind [[glucokinase]] (GK), thereby controlling both activity and intracellular location of this key [[enzyme]] of [[glucose]] [[metabolism]]. One of the important functions of GKRP is to maintain a reserve supply of GK in the nuclei for rapid release into the cytoplasm as the glucose begins to rise during a meal.
GKRP is a 68 kD protein of 626 [[amino acid]]s. It is coded for by a 19 [[exon]] [[gene]] on the short arm of [[chromosome]] 2 (2p23).
In hepatocytes of various [[mammal]]s, GKRP has always been found in molar excess of the amount of GK, but the GKRP:GK ratio varies according to diet, [[insulin]] sufficiency, and other factors. Free GKRP shuttles between the [[Cell nucleus|nucleus]] and the [[cytoplasm]]. It may be attached to the microfilament [[cytoskeleton]].
GKRP competes with glucose to bind with GK, but inactivates it when bound. In conditions of low glucose, GKRP then pulls the GK into the nucleus. Rising amounts of glucose coming into the hepatocyte prompt the GKRP to rapidly release GK to return to the cytoplasm.
[[Fructose]] and [[sorbitol]] can both be converted to [[fructose-1-phosphate]], which inhibits GKRP and frees GK. [[Fructose-6-phosphate]] binds to the same site of GKRP, but enhances the ability of GKRP to bind and inactivate GK.
The glucokinase of "[[knockout mouse|knockout mice]]" who lack GKRP is entirely found in the cytoplasm. They do not respond rapidly to glucose, exhibiting [[impaired glucose tolerance]]. [[Mutation]]s of the GKRP gene in humans have been sought as possible forms of monogenic [[diabetes]], but no examples have yet been discovered.
Trace amounts of GKRP have also been detected in [[lung]], in [[pancreas|pancreatic]] [[islet]] cells, and in periventricular [[neuron]]s of the [[hypothalamus]] in [[rat]]s, but physiological function and significance in these organs are unknown.
GKRP was discovered by Emile van Schaftingen and reported in 1989.
==References==
Van Schaftingen E (1989). A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose-6-phosphate and fructose-1-phosphate. Eur J Biochem 179:179-184. {{Entrez Pubmed|2917560}}
For more recent reviews, see Matschinsky FM, Magnuson MA, eds. '''Glucokinase and Glycemic Disease: From Basics to Novel Therapeutics'''. Basel:Karger, 2004. ISBN 3-8055-7744-3.
[[Category:Proteins]]