Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: A sequestration mechanism in metabolic regulation
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Glucokinase and glucokinase regulatory protein: mutual dependence for nuclear localization.
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. The regulatory protein, which was undetectable in the basal state, could be induced by doxycycline to levels comparable t...
متن کاملKinetic evidence for a 'mnemonical' mechanism for rat liver glucokinase.
Inhibition studies of glucokinase were carried out with the products of the reaction, glucose 6-phosphate and MgADP-, as well as with ADP3-, Mg2+ and ATP4-. The results of these, together with those of kinetic studies of the uninhibited reaction described previously [Storer & Cornish-Bowden (1976) Biochem. J. 159, 7-14], indicate that the enzyme obeys a 'mnemonical' mechanism. This implies that...
متن کاملInsulin-Receptor Substrate-2 (IRS-2) Is Required for Maintaining Glucokinase and Glucokinase Regulatory Protein Expression in Mouse Liver
Insulin receptor substrate (IRS) proteins play important roles in hepatic nutrient homeostasis. Since glucokinase (GK) and glucokinase regulatory protein (GKRP) function as key glucose sensors, we have investigated the expression of GK and GKRP in liver of Irs-2 deficient mice and Irs2(-/-) mice where Irs2 was reintroduced specifically into pancreatic β-cells [RIP-Irs-2/IRS-2(-/-)]. We observed...
متن کاملMolecular basis for the role of glucokinase regulatory protein as the allosteric switch for glucokinase.
Glucokinase (GK) is a monomeric allosteric enzyme and plays a pivotal role in blood glucose homeostasis. GK is regulated by GK regulatory protein (GKRP), and indirectly by allosteric effectors of GKRP. Despite the critical roles of GK and GKRP, the molecular basis for the allosteric regulation mechanism of GK by GKRP remains unclear. We determined the crystal structure of Xenopus GK and GKRP co...
متن کاملRole of Glucokinase in the Subcellular Localization of Glucokinase Regulatory Protein
Glucokinase (GCK) is the rate-limiting enzyme of liver glucose metabolism. Through protein-protein interactions, glucokinase regulatory protein (GCKR) post-transcriptionally regulates GCK function in the liver, and causes its nuclear localization. However the role of GCK in regulating GCKR localization is unknown. In the present study, using in vitro and in vivo models, we examined the levels o...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 1999
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.96.25.14511