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

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

Phosphofructokinase from rat heart perfused with epinephrine was purified to homogeneity and various allosteric properties were determined under conditions which approximate physiological concentrations of the substrates, effectors, and pH. The molecular weights of the protomer of the enzyme isolated from the hormone-stimulated and the control hearts are both approximately 83,000. The epinephrine-stimulated and the control enzymes contain 1.1 and 0.66 mol of phosphate/mol of protomer, respectively. Both enzymes can be fully phosphorylated by cAMP-dependent protein kinase indicating that the phosphorylation site is new and distinct from the known phosphorylation site of skeletal muscle phosphofructokinase. Pure phosphofructokinase isolated from the epinephrine-stimulated heart is significantly less sensitive to inhibition by ATP and citrate, and the K0.5 values for Fru-6-P (0.18 mM) and Fru-2,6-P2 (3 microM) are one-half those for the enzyme from control hearts. In the presence of in vivo concentrations of ATP, citrate, and Fru-6-P at pH 7.1, both enzymes are inactive in the absence of Fru-2,6-P2. Moreover, the K0.5 values for Fru-2,6-P2 of the hormone-stimulated and untreated enzymes are 3 and 6 microM, respectively. These differences in the allosteric properties of phosphofructokinases from the hormone-treated and the control hearts disappear when the enzymes are dephosphorylated by alkaline phosphatase. Determination of the glycolytic intermediates showed a 2-fold increase in Fru-6-P, Fru-2,6-P2, and AMP and 13-fold increase in Fru-1,6-P2. Partially purified Fru-6-P,2-kinase from epinephrine-stimulated and control hearts show KFru-6-P0.5 = 4 and 15 microM, respectively. These results indicate that rat heart phosphofructokinase in vivo requires Fru-2,6-P2 for its activity. Epinephrine stimulates phosphorylation of phosphofructokinase which results in a more active form. The hormone also increases Fru-2,6-P2 which appears to be the result of an activation of Fru-6-P,2-kinase by a covalent modification.
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PMID:Regulation of phosphofructokinase in perfused rat heart. Requirement for fructose 2,6-bisphosphate and a covalent modification. 316 Jul 3

It is evident from the above review that during the last two decades a great deal of interest in investigating the action of serotonin in parasitic worms has been shown by parasitologists as well as by scientists from several other disciplines. What we have initially reported concerning the effect of serotonin on motility and carbohydrate metabolism of F. hepatica has been pursued on several other parasitic worms. The studies so far indicate that serotonin stimulates motility of every species tested among the phylum Platyhelminthes. The indoleamine also stimulates glycogenolysis in the few flatworm parasites that have been investigated. The information in nematodes is scanty and the role of serotonin in these parasites is still open for experimentation. Recent biochemical investigations on F. hepatica and S. mansoni demonstrated that serotonin and related compounds utilize a common class of receptors in plasma membrane particles which I designate as 'serotonin receptors'. These receptors are linked to an adenylate cyclase that catalyses the synthesis of the second messenger, cyclic 3',5'-AMP. Serotonin and its congeners increase the concentration of cyclic AMP in intact parasites whereas antagonists inhibit such an effect. Cyclic AMP stimulates glycogenolysis, glycolysis and some rate-limiting glycolytic enzymes. It activates a protein kinase that may be involved in activation of glycogen phosphorylase and phosphofructokinase. Serotonin-activated adenylate cyclase in S. mansoni is activated early in the life of the schistosomule. The possibility is discussed that the availability of cyclic AMP through serotonin activation in these parasites may be a prelude to the development processes that take place in the parasite. The different components of the serotonin-activated adenylate cyclase in the parasite are the same as those that have been previously described for the host. Binding characteristics of the receptors indicate that the receptors in F. hepatica appear to be different from those that have been described in the host. The discovery of these receptors and their differences from those in the host offer a new site which is amenable to pharmacological manipulation. The search for new agents that influence serotonin receptors in these parasites could be included in a strategy for the development of new chemotherapeutic agents against these parasites.
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PMID:Serotonin receptors in parasitic worms. 615 76

In vivo phosphorylation of muscle proteins has been studied by incorporation of [32P]phosphate with emphasis placed upon the phosphorylation of glycolytic enzymes. Of the approximately 25 soluble proteins resolved by two-dimensional electrophoresis that contain significant 32P, phosphofructokinase was the sole glycolytic enzyme identified as a phosphoprotein. The extent of phosphorylation found for this enzyme was the same as determined previously for purified phosphofructokinase and was about the same as the extent of phosphorylation of phosphorylase in resting muscle. Subsequent partial purification of several glycolytic enzymes confirmed the absence of significant amount of phosphate. However, phosphoglycerate mutase contained small amounts of covalently bound 32P that was exchangeable with 3-phosphoglycerate and therefore, most likely was incorporated during the catalytic reaction cycle. Analogous results were obtained for phosphoglucomutase. Both mutases were also phosphorylated at the same sites by the catalytic subunit of cyclic AMP-dependent protein kinase.
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PMID:Relative phosphate contents of phosphofructokinase and other soluble phosphoproteins in skeletal muscle. 621 87

Low phosphate and high phosphate forms of phosphofructokinase (Furuya, E., and Uyeda, K. (1980) J. Biol. Chem. 255, 11656-11659) from rat liver were purified to homogeneity and various properties were compared. The specific activities of these enzymes and their electrophoretic mobilities on polyacrylamide in sodium dodecyl sulfate are the same. A limited tryptic digestion yields products with no change in the enzyme activity but with a reduction in the molecular weight of about 2000. Both low and high phosphate enzymes can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase, and approximately twice as much [32P]phosphate is incorporated into the low phosphate than the high phosphate enzyme. A comparison of their allosteric kinetic properties reveal that the high phosphate enzyme is much more sensitive to inhibition by ATP and citrate and shows a higher K0.5 for fructose 6-phosphate than the low phosphate enzyme, and the difference in the K0.5 values becomes greater at lower pH values. Furthermore, the high phosphate phosphofructokinase is less sensitive to activation by AMP and fructose 2,6-bisphosphate. Moreover, when the low phosphate enzyme is phosphorylated by protein kinase, the resulting phosphorylated enzyme exhibits a higher K0.5 for fructose 2,6-bisphosphate than does the untreated enzyme. These results demonstrate that the phosphorylation affects the allosteric kinetic properties of the enzyme and results in a less active form of phosphofructokinase.
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PMID:Differences in the allosteric properties of pure low and high phosphate forms of phosphofructokinase from rat liver. 622 34

In polymorphonuclear leukocytes from severely diabetic patients the rate of glycolysis is decreased due to decreased activity of phosphofructokinase, and the glycogen content and rate of glycogen synthesis are decreased due to a decreased total activity of glycogen synthase and an impaired activation of this enzyme. Covalent modification of glycogen synthase by phosphorylation creates a continuum of phosphorylated enzyme forms of decreasing activity. Phosphorylation of a single peptide, whether by the synthase kinase or the cyclic AMP dependent protein kinase, is critical for the associated kinetic changes during the initial phosphorylation. Conversely, dephosphorylation of this particular peptide is associated with complete activation. The protein phosphatase activity of the microsomal fraction may be separated into functionally and possibly also structurally different phosphorylase- and synthase-phosphatase activities, where the latter appears to be dependent on free cytoplasmic Ca2+. It is hypothesized that it is synthase-phosphatase activity that is absent in leukocytes from diabetic patients and is restored upon insulin treatment.
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PMID:The polymorphonuclear leukocyte in diabetes mellitus. 622 61

Rabbit brain phosphofructokinase was purified to homogeneity by a rapid procedure involving affinity chromatography and gel filtration. The enzyme consists of hybrids of the three phosphofructokinase subunit types C, A, and B. The molecular weights of these subunits are 86,000, 84,000, and 80,000, respectively; they are present in brain phosphofructokinase in a ratio of approximately 5:4:1.5. The enzyme as isolated from rabbit brain contains 0.16-0.18 mol phosphate per mole of subunit; another 0.4-0.5 mol phosphate per mole subunit can be incorporated in vitro in the presence of the catalytic subunit of cyclic AMP-dependent protein kinase. The initial rate of phosphorylation is increased by fructose 2,6-bisphosphate or AMP and decreased by citrate or high concentrations of ammonium sulfate. All three subunit types are phosphorylated in vitro, and the phosphorylation site on each subunit is sensitive to cleavage by trypsin at a terminal region of each subunit. However, these sites show different relative rates of phosphorylation in vitro in the presence of ammonium sulfate. In vitro phosphorylation of brain phosphofructokinase had no affect on specific activity, inhibition by ATP, or activation by fructose 2,6-bisphosphate.
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PMID:Isozyme composition and phosphorylation of brain phosphofructokinase. 623 51

The effect of cAMP-dependent protein kinases from rabbit skeletal muscles on Ca2+ uptake by fragments of skeletal muscle sarcoplasmic reticulum was studied. It was shown that incubation of the sarcoplasmic reticulum fragments with protein kinase increases the rate of Ca2+ uptake without changing the activity of Ca2+-dependent ATPase. This phenomenon is not accompanied by phosphorus incorporation into the protein components of the reticulum membranes. The protein kinase preparation subjected to "self-phosphorylation" is also capable to increase the rate of Ca2+ uptake. Using (14C) -oleic acid, it was shown that the increase of the rate of Ca2+ transport under effects of the "self-phosphorylated" protein kinase occurs due to the binding of free fatty acids present in the sarcoplasmic reticulum membranes. It was found that the effect observed is due to phosphofructokinase (ATP : D-fructose-6-phosphate-1-phosphotransferase) present in the protein kinase preparation.
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PMID:[Cause of increase in the efficiency of Ca2+ transport by fragments of sarcoplasmic reticulum from fast skeletal muscles induced by protein kinase]. 624 73

Addition of glucagon to isolated hepatocytes reduced the activity of 6-phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40). Phosphorylation contributed to the inhibition of pyruvate kinase, but several lines of evidence indicated that this reaction was not responsible for the inhibition of phosphofructokinase. First, the increase in phosphorylation in intact cells induced by increasing the concentration of glucagon did not correlate well with the decrease in enzyme activity. Second, phosphorylation of phosphofructokinase induced by addition of cyclic AMP and Mg2+-ATP or by addition of Mg2+-ATP and the catalytic subunit of the cyclic AMP-dependent protein kinase to hepatocyte extracts had no effect on enzyme activity. Third, ammonium sulfate precipitation of the enzyme from extracts of cells incubated with glucagon abolished the hormone effect. The effect could be restored, however, by the addition of a phosphofructokinase-free extract from glucagon-treated cells to the ammonium sulfate-treated enzyme from either untreated or glucagon-treated cells. These results suggest that the inhibition of phosphofructokinase by glucagon is due to changes in the level of an allosteric effector(s).
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PMID:Mechanism of action of glucagon on hepatocyte phosphofructokinase activity. 625 41

Phosphorylation of rabbit skeletal muscle phosphofructokinase by the catalytic subunit of cyclic AMP-dependent protein kinase occurs with a Km of about 230 microM and Vmax approaching that seen with histone as a substrate. The rate of phosphorylation of phosphofructokinase by protein kinase is increased by allosteric activators of phosphofructokinase, whereas inhibitors of phosphofructokinase inhibit the phosphorylation. Inhibitors and activators change Vmax but not Km. The site of phosphorylation is a serine residue that is the sixth amino acid from the carboxyl terminus. Limited proteolysis by trypsin releases an octapeptide from the carboxyl terminus and a brief exposure to subtilisin releases a dodecapeptide from the carboxyl end. The sequence of the dodecapeptide is His-Ile-Ser-Arg-Lys-Arg-Ser(P)-Gly-Glu-Ala-Thr-Val. Phosphofructokinase isolated from a rabbit injected 18 h prior to killing with [32P]PO4 contained covalently bound radioactive phosphate. Approximately 80% of the phosphate was released in a trichloroacetic acid-soluble form following limited proteolysis by trypsin, under which conditions the enzyme remained with a monomer size of about 80,000 daltons. The position of elution from Sephadex G-25 of the phosphopeptide was identical with that found following limited trypsin proteolysis of in vitro labeled enzyme. Migration of the phosphopeptides on thin layer cellulose chromatography was also identical. We conclude that at least 80% of the radioactive phosphate introduced within 18 h of an intravenous injection of [32P]PO4 is found at the same site as that introduced by phosphorylation with the catalytic subunit of cyclic AMP-dependent protein kinase.
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PMID:Studies on the phosphorylation of muscle phosphofructokinase. 626 42

p-Fluorosulfonylbenzoyl 5'-adenosine (FSO2BzAdo) was shown previously to be an irreversible inhibitor of the catalytic subunit of cAMP-dependent protein kinase II from porcine skeletal muscle (Zoller, M. J., and Taylor, S. S. (1979) J. Biol. Chem. 254, 8363-8368). The catalytic subunit of porcine heart cAMP-dependent protein kinase was also inhibited following incubation with FSO2[14C]BzAdo, and inhibition was shown to result from the stoichiometric, covalent modification of a single lysine residue. The amino acid sequence in an extended region around the carboxybenzenesulfonyl lysine (CBS-lysine) was elucidated by characterizing both tryptic and cyanogen bromide peptides containing the 14C-modified residue. The sequence in this region was Leu-Val-Lys-His-Lys-Glu-Thr-Gly-Asn-His-Phe-Ala-Met-Lys(CBS)-Ile-Leu-Asp-Lys-Glu-Lys-Val-Val-Lys-Leu-Lys-Gln-Ile. The covalently modified residue corresponded to lysine 71 in the overall polypeptide chain. Homologies to bovine heart catalytic subunit and to a site modified by FSO2BzAdo in phosphofructokinase are considered.
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PMID:Affinity labeling of cAMP-dependent protein kinase with p-fluorosulfonylbenzoyl adenosine. Covalent modification of lysine 71. 627 Jan 32


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