Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rates of glycolysis and glycogenolysis an the rate of lactate formation from glucoso-6-phosphate (G-6-Ph) in the liver were reduced during stress (starvation). On the contrary, these activities in the adrenals were increased. The rates of lactate formation from fructose diphosphate remained unchanged in both organs. The results obtained attest to the inhibition in the liver and activation in the adrenals of phosphorylase, hexokinase and phosphofructokinase. The degree of hexokinase inhibition in the liver depended on the presence of cAMP, ATP and MgCl2 in the incubation medium and was a consequence of enzymatic phosphorylation. Unlike 2', 3'-AMP, the inhibitory effect of CAMP was highly specific. The protein inhibitor of protein kinase completely reversed the inhibitory effect of cAMP on hexokinase. In the adrenals, cAMP slightly increased the rates of glycolysis and lactate formation from G-6-Ph because of allosteric effects of cAMP. The activation rather than inhibition of glycolysis in the adrenals during stress is probably caused by the absence in this tissue of cAMP-dependent protein kinase which phosphorylates hexokinase.
...
PMID:[Effect of cAMP of glycolysis and glycogenolysis in the liver and adrenals of white rats]. 627 Dec 95

Glucagon stimulates gluconeogenesis in part by decreasing the rate of phosphoenolpyruvate disposal by pyruvate kinase. Glucagon, via cyclic AMP (cAMP) and the cAMP-dependent protein kinase, enhances phosphorylation of pyruvate kinase, phosphofructokinase, and fructose-1,6-bisphosphatase. Phosphorylation of pyruvate kinase results in enzyme inhibition and decreased recycling of phosphoenolpyruvate to pyruvate and enhanced glucose synthesis. Although phosphorylation of 6-phosphofructo 1-kinase and fructose-1,6-bisphosphatase is catalyzed in vitro by the cAMP-dependent protein kinase, the role of phosphorylation in regulating the activity of and flux through these enzymes in intact cells is uncertain. Glucagon regulation of these two enzyme activities is brought about primarily by changes in the level of a novel sugar diphosphate, fructose 2,6-bisphosphate. This compound is an activator of phosphofructokinase and an inhibitor of fructose-1,6-bisphosphatase; it also potentiates the effect of AMP on both enzymes. Glucagon addition to isolated liver systems results in a greater than 90% decrease in the level of this compound. This effect explains in large part the effect of glucagon to enhance flux through fructose-1,6-bisphosphatase and to suppress flux through phosphofructokinase. The discovery of fructose 2,6-bisphosphate has greatly furthered our understanding of regulation at the fructose 6-phosphate/fructose 1,6-bisphosphate substrate cycle.
...
PMID:Regulation by glucagon of hepatic pyruvate kinase, 6-phosphofructo 1-kinase, and fructose-1,6-bisphosphatase. 628 62

A new activator of phosphofructokinase, which is bound to the enzyme and released during its purification, has been discovered. Its structure has been determined as beta-D Fructose-2,6-P2 by chemical synthesis, analysis of various degradation products and NMR. D-Fructose-2,6-P2 is the most potent activator of phosphofructokinase and relieves inhibition of the enzyme by ATP and citrate. It lowers the Km for fructose-6-P from 6 mM to 0.1 mM. Fructose-6-P,2-kinase catalyzes the synthesis of fructose-2,6-P2 from fructose-6-P and ATP, and the enzyme has been partially purified. The degradation of fructose-2,6-P2 is catalyzed by fructose-2,6-bisphosphatase. Thus a metabolic cycle could occur between fructose-6-P and fructose-2,6-P2, which are catalyzed by these two opposing enzymes. The activities of these enzymes can be controlled by phosphorylation. Fructose-6-P,2-kinase is inactivated by phosphorylation catalyzed by either cAMP dependent protein kinase or phosphorylase kinase. The inactive, phospho-fructose-6,P,2-kinase is activated by dephosphorylation catalyzed by phosphorylase phosphatase. On the other hand, fructose-2,6-bisphosphatase is activated by phosphorylation catalyzed by cAMP dependent protein kinase. Investigation into the hormonal regulation of phosphofructokinase reveals that glucagon stimulates phosphorylation of phosphofructokinase which results in decreased affinity for fructose-2,6-P2 appears to be due to the decreased synthesis by inactivation of fructose-2,6-P2,2-kinase and increased degradation as a result of activation of fructose-2,6-bisphosphatase. Such a reciprocal change in these two enzymes has been demonstrated in the hepatocytes treated by glucagon and epinephrine. The implications of these observations in respect to possible coordinated controls of glycolysis and glycogen metabolism are discussed.
...
PMID:Fructose-2,6-P2, chemistry and biological function. 629 99

In hepatocytes 32P-incorporation into rat liver phosphofructokinase is stimulated by glucose as well as by glucagon, the effects of both stimuli being prevented by L-alanine [Eur. J. Biochem. (1982) 122, 175]. The phosphopeptides of the enzyme derived from limited proteolysis by subtilisin and from exhaustive tryptic digestion were analyzed either by one-dimensional mapping on sodium dodecyl sulphate-polyacrylamide slab gels and by fingerprint mapping, respectively. It is shown that in vivo stimulation of 32P-incorporation by glucose or by glucose plus glucagon results in identical phosphopeptide maps, and that these maps were identical with those obtained from phosphofructokinase phosphorylated in vitro with catalytic subunit of cAMP-dependent protein kinase. It is concluded that in the intact liver cell phosphofructokinase is phosphorylated by cAMP-dependent protein kinase but that the state of phosphorylation is modified by metabolite control.
...
PMID:Metabolite-controlled phosphorylation of hepatic phosphofructokinase proceeds by cAMP-dependent protein kinase. 629 95

Phosphoprotein phosphatase was purified from swine kidney by chromatography on DEAE-Sephadex A-50, Sephacryl S-200 and Sepharose 4B columns containing covalently bound hexanediamine and polylysine. The enzyme was purified more than 20000-fold and the homogeneous preparation had a specific activity of 2.8 micromol per min per mg of protein with saturating concentrations of 32P-histone as the substrate. The phosphatase showed only a single protein band when examined by polyacrylamide gel electrophoresis and a single protein peak containing all of the enzymatic activity was observed during chromatography on Sephadex G-100 column. The molecular weight of the purified enzyme was determined to be 70000 +/- 5000 by exclusion chromatography on a calibrated Sephadex G-100 column. Similar values were obtained by sucrose density centrifugation, 70000 +/- 5000, and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, 70000 +/- 3000. The purified enzyme catalyzed the dephosphorylation of the phosphorylated forms of glycogen synthase, phosphorylase, histone, phosphofructokinase, Type II regulatory subunit of cyclic AMP-dependent protein kinase, casein and protamine. The apparent Km values for these substrates were 3.6 microM, 2.8 microM, 66 microM, 3.3 microM, 8.0 microM, 6.6 microM and 100 microM, respectively. The enzyme did not hydrolyze low molecular weight phosphate esters such as glucose 6-phosphate, glycerol phosphate, adenosine nucleotides and inorganic pyrophosphate. The activity of the enzyme towards a phosphorylated protein substrate was competitively inhibited by the addition of other substrates. These results suggest that swine kidney contains a phosphoprotein phosphatase with a rather broad substrate specificity for a number of endogenous and exogenous phosphoprotein substrates.
...
PMID:Purification and properties of swine kidney phosphoprotein phosphatase. 630 89

On the basis of kinetic activation assays, the apparent affinity of muscle phosphofructokinase for fructose 2,6-bisphosphate was about 9-fold greater than that for fructose 1,6-bisphosphate, which in turn was about 10 times higher than that for glucose 1,6-bisphosphate. Equilibrium binding experiments showed that both fructose bisphosphates bind to phosphofructokinase with negative cooperativity; the affinity for fructose 2,6-bisphosphate was about 1 order of magnitude greater than the affinity for fructose 1,6-bisphosphate. Binding of fructose 2,6-bisphosphate to phosphofructokinase was antagonized by fructose 1,6-bisphosphate and glucose 1,6-bisphosphate and vice versa. Both fructose bisphosphates promoted aggregation of the enzyme to higher polymers as indicated by sucrose density gradient centrifugation. Other indicators of phosphofructokinase conformation such as thiol reactivity and maximum activation of in vitro phosphorylation by the catalytic subunit of cyclic AMP-dependent protein kinase gave identical results in the presence of fructose 2,6-bisphosphate, fructose 1,6-bisphosphate, or glucose 1,6-bisphosphate, indicating a common conformation is produced by all three ligands. It is concluded that the sugar bisphosphates bind to a single site on the enzyme.
...
PMID:Binding of hexose bisphosphates to muscle phosphofructokinase. 631 44

A phosphoprotein phosphatase has been purified from rat liver cytosol. The purification involved chromatography on DEAE-cellulose. Sephacryl S-200, fast protein liquid chromatography (FPLC) and sucrose density gradient centrifugation. It resulted in an almost homogeneous enzyme with a relative molecular mass, Mr, of 90 000 by gel filtration and sucrose gradient centrifugation and Mr = 44 500 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). Therefore it seems to be a dimeric enzyme. This protein phosphatase (termed PFK-phosphatase) is completely dependent on Mg2+, which can be replaced partly by Mn2+. It can be eluted from DEAE-cellulose with 120 mM NaCl, is not affected by Ca2+, 100 microM trifluoperazine or the heat-stable inhibitor-2. Inhibition occurs with phosphate, ammonium sulfate and fluoride. PFK-phosphatase dephosphorylates preferentially the alpha subunit of phosphorylase kinase (alpha/beta dephosphorylation ratio 5-10). Phosphorylase a, mixed histone and casein do not serve as substrates. The enzyme dephosphorylates effectively the key enzymes of glucose metabolism 6-phosphofructo-1-kinase, fructose 1,6-bisphosphatase, pyruvate kinase and 6-phosphofructo-2-kinase. Using this protein phosphatase and the catalytic subunit of cAMP-dependent protein kinase, a complete phosphorylation, dephosphorylation and rephosphorylation cycle was possible with 6-phosphofructo-1-kinase as substrate.
...
PMID:Purification and characterization of a protein phosphatase from rat liver acting on key enzymes of glucose metabolism. 632 87

A chloromethyl ketone derivative of lactic acid is a potent inhibitor of glycolysis of Ehrlich ascites tumor cells. It inhibited glycolysis of intact cells by about 50% at 200 microM (100 nmol/mg of protein) while cell-free extracts were inhibited 50% at 50 microM (50 nmol/mg of protein). N alpha-(p-Tosyl)-L-lysine chloromethyl ketone and N alpha-(p-tosyl)-L-phenylalanine chloromethyl ketone inhibited only slightly or not at all at this concentration. The inhibition was localized at the hexokinase and phosphofructokinase steps since these two enzymes added to an inactivated extract restored the glycolytic activity, whereas none of the other glycolytic enzymes did. In fact, addition of pyruvate kinase or lactate dehydrogenase, which stimulated glycolysis, resulted in a more pronounced inhibition. Glycolysis and hexokinase activities in extracts of Rous sarcoma virus transformed cells were considerably more sensitive to the inhibitor than the activities from normal chick embryo fibroblasts. Hexokinase from mouse brain required 50 times higher concentrations for inhibition than the enzyme from mouse Ehrlich ascites tumor cells. Yeast hexokinase was unaffected at all concentrations tested. Since 5,5'-dithiobis(2-nitrobenzoate) protected against the inhibition, the chloromethyl ketone appeared to inhibit by interaction with an essential SH group. A pronounced inhibition of protein kinase activity of plasma membranes of Ehrlich ascites tumor cells was observed in the presence of the chloromethyl ketone. As in the case of glycolysis, the chloromethyl ketone of lactic acid was a more potent inhibitor of protein kinase activity than several other chloromethyl ketones that were tested.
...
PMID:Inhibition of hexokinase and protein kinase activities of tumor cells by a chloromethyl ketone derivative of lactic acid. 710 7

We determined the activity of phosphofructokinase (PFK), a rate-limiting enzyme of glycolysis, in the rat oocyte during maturation either by luteinizing hormone stimulation in vivo or by cultivation under various conditions. In vivo, the activity of PFK in the maturing oocyte increased significantly, suggesting that the glycolytic pathway developed as the first meiotic division proceeded. A breakdown of the germinal vesicle and an increased activity of PFK were observed when denuded oocytes were cultured. Treatment of the oocytes with dibutyryl cAMP and 3-isobutyl-1-methyl xanthine almost completely inhibited germinal breakdown, whereas the activity of PFK increased significantly. The data suggest that regulation of PFK activity is not directly dependent on cAMP or cAMP-dependent protein kinase, and is not necessarily dependent on meiotic maturation. Our study also revealed that epidermal growth factor (EGF) significantly increased PFK activity, showing that EGF may be a potent inducer of oocyte maturation.
...
PMID:Phosphofructokinase activity as a measure of maturation of rat oocytes developed in vivo and in vitro. 752 6

Organ slices from the turtle Trachemys scripta elegans were incubated under aerobic and anoxic conditions to examine the effect of protein kinase (PrK) second messengers in potentiating the biochemical responses to anoxia exposure. Incubating liver slices from aerobic animals under anoxic conditions produced biochemical changes exactly similar to those observed in vivo: phosphofructokinase (PFK) was more sensitive to citrate inhibition and the percentage of glycogen phosphorylase (GP) in the active a form increased. On the other hand, incubating brain and heart tissue slices under anoxic conditions produced no changes in PFK and GP kinetic constants. Addition of PrK second messengers (dibutyryl-cAMP or Ca2+ plus phorbol myristate acetate) to the incubated tissues did not promote anoxia-associated changes in aerobically incubated tissues nor did they prevent anoxia-associated changes in anaerobically incubated tissues. These results suggest that unidentified external hormonal signals mediate heart and brain responses to anoxia. It is also apparent that cAMP and Ca2+ plus phospholipid do not play a role in bringing about the anoxia-induced changes in PFK, GP and fructose 2,6-bisphosphate in liver of turtles.
...
PMID:Effect of anoxia on isolated turtle tissues: is the response to anoxia mediated by protein kinase second messengers? 769 98


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---