Biomaterial Database

Phosphorylation of glycolytic and gluconeogenic enzymes by the insulin receptor kinase. 1987

E M Sale, and M F White, and C R Kahn

Various glycolytic and gluconeogenic enzymes were tested as substrates for the insulin receptor kinase. Phosphofructokinase and phosphoglycerate mutase were found to be the best substrates. Phosphorylation of these enzymes was rapid, stimulated 2- to 6-fold by 10(-7) M insulin and occurred exclusively on tyrosine residues. Enolase, fructose 1,6-bisphosphatase, lactate dehydrogenases in decreasing order, were also subject to insulin-stimulated phosphorylation but to a smaller extent than that for phosphofructokinase or phosphoglycerate mutase. The phosphorylation of phosphofructokinase was studied most extensively since phosphofructokinase is known to catalyze a rate-limiting step in glycolysis. The apparent Km of the insulin receptor for phosphofructokinase was 0.1 microM, which is within the physiologic range of concentration of this enzyme in most cells. Tyrosine phosphorylation of phosphofructokinase paralleled autophosphorylation of the beta-subunit of the insulin receptor with respect to time course, insulin dose response (half maximal effect between 10(-9) and 10(-8) M insulin), and cation requirement (Mn2+ greater than Mg2+ much greater than Ca2+). Further study will be required to determine whether the tyrosine phosphorylation of phosphofructokinase plays a role in insulin-stimulated increases in glycolytic flux.

UI	MeSH Term	Description	Entries
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007770	L-Lactate Dehydrogenase	A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.	Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D010732	Phosphofructokinase-1	An allosteric enzyme that regulates glycolysis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-1,6-bisphosphate. D-tagatose- 6-phosphate and sedoheptulose-7-phosphate also are acceptors. UTP, CTP, and ITP also are donors. In human phosphofructokinase-1, three types of subunits have been identified. They are PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE; PHOSPHOFRUCTOKINASE-1, LIVER TYPE; and PHOSPHOFRUCTOKINASE-1, TYPE C; found in platelets, brain, and other tissues.	6-Phosphofructokinase,6-Phosphofructo-1-kinase,Fructose-6-P 1-Kinase,Fructose-6-phosphate 1-Phosphotransferase,6 Phosphofructokinase,Phosphofructokinase 1
D010750	Phosphoproteins		Phosphoprotein
D010751	Phosphopyruvate Hydratase	A hydro-lyase that catalyzes the dehydration of 2-phosphoglycerate to form PHOSPHOENOLPYRUVATE. Several different isoforms of this enzyme exist, each with its own tissue specificity.	Enolase,Neuron-Specific Enolase,2-Phospho-D-Glycerate Hydro-Lyase,2-Phospho-D-Glycerate Hydrolase,2-Phosphoglycerate Dehydratase,Enolase 2,Enolase 3,Muscle-Specific Enolase,Nervous System-Specific Enolase,Non-Neuronal Enolase,alpha-Enolase,beta-Enolase,gamma-Enolase,2 Phospho D Glycerate Hydro Lyase,2 Phospho D Glycerate Hydrolase,2 Phosphoglycerate Dehydratase,Dehydratase, 2-Phosphoglycerate,Enolase, Muscle-Specific,Enolase, Nervous System-Specific,Enolase, Neuron-Specific,Enolase, Non-Neuronal,Hydratase, Phosphopyruvate,Hydro-Lyase, 2-Phospho-D-Glycerate,Muscle Specific Enolase,Nervous System Specific Enolase,Neuron Specific Enolase,Non Neuronal Enolase,System-Specific Enolase, Nervous,alpha Enolase,beta Enolase,gamma Enolase
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011505	Protein-Tyrosine Kinases	Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.	Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011972	Receptor, Insulin	A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.	Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D001731	Bisphosphoglycerate Mutase	An enzyme that catalyzes the transfer of phosphate from C-3 of 1,3-diphosphoglycerate to C-2 of 3-phosphoglycerate, forming 2,3-diphosphoglycerate. EC 5.4.2.4.	Diphosphoglyceromutase,Bisphosphoglycerate Synthase,Bisphosphoglyceromutase,Diphosphoglycerate Mutase,Mutase, Bisphosphoglycerate,Mutase, Diphosphoglycerate,Synthase, Bisphosphoglycerate