Disease relevance of Gckr

• Random peptide phage display library screening for binding partners of GRP allowed the identification of an asparagine-leucine consensus motif [1].
• Conditional expression of the glucokinase regulatory protein in insulinoma cells, under control of the reverse tetracycline-dependent transactivator, was used to investigate whether expression of this protein de novo would alter the intracellular distribution of glucokinase [2].
• Here we describe the structure of full-length (2.2 kb) cDNA for human GCKR, from the hepatoblastoma cell line HepG2 [3].

High impact information on Gckr

• Gene expression of glucokinase regulatory protein in regenerating rat liver [4].
• The glucokinase regulatory protein (GRP) plays a pivotal role in the regulation of metabolic flux in liver by the glucose-phosphorylating enzyme glucokinase [1].
• A novel glucokinase regulator in pancreatic beta cells: precursor of propionyl-CoA carboxylase beta subunit interacts with glucokinase and augments its activity [5].
• A glucokinase regulatory protein has been reported to exist in the liver, which suppresses enzyme activity in a complex with fructose 6-phosphate, whereas no corresponding protein has been found in pancreatic beta cells [5].
• Our results show that the mechanism comprising glucokinase and GKRP confers a markedly extended responsiveness and sensitivity to changes in glucose concentration on the hepatocyte [6].

Biological context of Gckr

• GKRP had a negative control coefficient of glycogen synthesis that is slightly greater than unity (-1.2) and a control coefficient on glycolysis of -0 [6].
• Adenovirus-mediated overexpression of GKRP (by up to 2-fold above endogenous levels) increased glucokinase binding and inhibited glucose phosphorylation, glycolysis, and glycogen synthesis over a wide range of concentrations of glucose and sorbitol [6].
• RESULTS: Hepatocytes from fa/fa rats have higher glucokinase activity and expression of the glucokinase regulatory protein and higher rates of glycolysis and lipogenesis, but lower rates of glycogen synthesis than hepatocytes from Fa/? controls [7].
• Evidence for glucose and sorbitol-induced nuclear export of glucokinase regulatory protein in hepatocytes [8].
• Yeast artificial chromosomes (YAC clones) containing human GCKR were isolated, and the gene was mapped to Chromosome (Chr) 2p23 by fluorescent in situ hybridization and somatic cell hybrid analysis [3].

Anatomical context of Gckr

• Glucokinase regulatory protein is associated with mitochondria in hepatocytes [9].
• Anomeric specificity of human liver and B-cell glucokinase: modulation by the glucokinase regulatory protein [10].
• In both liver and pancreatic islet, glucokinase is subject to inhibition by a regulatory protein (GCKR) [3].

Associations of Gckr with chemical compounds

• In the presence of hexose 6-phosphates, partially purified islet glucokinase was inhibited by the hepatic glucokinase regulatory protein in a D-fructose-1-phosphate-sensitive manner [11].

Regulatory relationships of Gckr

• Hepatic glucokinase is inhibited by a 68-kDa glucokinase regulatory protein (GKRP) that is expressed in molar excess [6].

Analytical, diagnostic and therapeutic context of Gckr

• Also, using RT-PCR analysis we found a glucokinase regulatory protein mRNA similar to that previously reported in liver [12].

References