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)

Hormone-sensitive lipase partially purified from adipose tissue of laying hens was markedly activated by cyclic AMP-dependent protein kinase. Activation was approximately 4-fold (ranging up to as great as 10-fold) compared with the much lower degree of activation obtained with analogous preparations from rat and human adipose tissues (59 and 86%, respectively). The partially purified preparations contained adequate endogenous protein kinase activity to effect complete activation with addition of cyclic AMP, ATP, and Mg(2+). Activation was blocked by protein kinase inhibitor (from rabbit skeletal muscle) but could be restored fully by addition of excess exogenous protein kinase (from bovine skeletal muscle). The fully activated lipase was slowly deactivated by dialysis at 4 degrees C and then rapidly and almost fully reactivated by addition of cyclic AMP and ATP-Mg(2+). Reactivation was blocked by protein kinase inhibitor. This deactivation-reactivation cycle was rapid at 23 degrees C with dialysis against charcoal and could be demonstrated repeatedly using a single preparation. The reversible deactivation of protein kinase-activated enzyme is presumed to reflect the action of a lipase phosphatase. Lipase prepared from tissue previously exposed to glucagon yielded a much smaller degree of activation than lipase prepared from tissue not exposed to the lipolytic hormone, indicating that the physiological hormone-induced activation is probably similar to or identical with the protein kinase activation demonstrated in the cell-free preparations. Under the conditions of assay used, the partially purified lipase fraction contained diglyceride, monoglyceride, and lipoprotein lipase activities. However, treatment with cyclic AMP-dependent protein kinase had virtually no effect on these lipase activities.
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PMID:Reversible protein kinase activation of hormone-sensitive lipase from chicken adipose tissue. 437 88

1. Adrenaline has a biphasic effect on intracellular lipoprotein lipase activity and on endogenous triacylglycerol content in heparin-perfused heart. 2. A high concentration of adrenaline (1 microM in the perfusion buffer) activated endogenous lipoprotein lipase activity and, at the same time, decreased intracellular triacylglycerol stores. 3. In contrast, a low concentration (0.005 microM-adrenaline) inhibited intracellular lipoprotein lipase activity. Under these conditions, cardiac triacylglycerol content was elevated above control values. 4. Perfusing the heart with high and low concentrations of 3-isobutyl-1-methylxanthine elicited a biphasic effect on endogenous lipoprotein lipase activity and triacylglycerol content similar to that seen with adrenaline treatment. 5. The effect of adrenaline on intracellular lipoprotein lipase activity appears to be mediated by cyclic AMP through protein kinase. 6. A possible role for intracellular lipoprotein lipase in the regulation of endogenous triacylglycerol in rat heart is proposed.
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PMID:Possible role of lipoprotein lipase in the regulation of endogenous triacylglycerols in the rat heart. 617 39

Three macrophage cell lines, J774(2), CT2 and J7H1 were compared with respect to synthesis and secretion of lipoprotein lipase. The enzyme activity measured was characterized as lipoprotein lipase on the basis of serum dependence and inhibition by 1 M NaCl. Enzyme activity in all three lines increased with time in culture and the highest activity was found in the medium of the CT2 line which is adenylate cyclase deficient while that in the J7H1 line, cyclic AMP-dependent protein kinase deficient, was intermediate. The half life of the enzyme activity in conditioned medium from all three lines was 30-40 min, suggesting that the different levels of activity observed do represent different levels of enzyme production by the cells. About 80% of the lipoprotein lipase activity from all three lines was present in the medium and 50-70% of cellular activity could be released into the medium by a 3-min exposure to heparin. In addition, 24 h incubation with heparin enhanced enzyme secretion in all three lines. To determine the role of cyclic AMP in the regulation of lipoprotein lipase activity use was made of dibutyryl cAMP, methyl isobutylxanthine (IBMX) and cholera toxin. These agents strikingly depressed lipoprotein lipase activity in the J774(2) line but only dibutyryl cAMP was active in the CT2 line (adenylate cyclase deficient). In the J7H1 (protein kinase deficient) line there was no response to dibutyryl cAMP or IBMX over the first 4 h of incubation. Addition of these agents did not affect total cell protein synthesis. The present findings indicate that in the intact cells changes in cyclic AMP levels are associated with a change in the activity of lipoprotein lipase.
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PMID:Lipoprotein lipase activity in cultured macrophage cell line J774(2) and its increase in variants deficient in adenylate cyclase and cyclic AMP-dependent protein kinase. 618 77

Differentiation of 3T3-L1 fibroblasts to adipocyte-like cells was accompanied by a 19-fold increase in neutral triglyceride lipase activity, a 12-fold increase in diglyceride lipase activity, a 10-fold increase in monoglyceride lipase activity, and a 280-fold increase in cholesterol esterase activity. In contrast, acid acylhydrolase activities did not increase during differentiation. The rate of glycerol release from unstimulated intact cells increased by more than 1 order of magnitude upon differentiation. Isoproterenol (1 microM) and 1-methyl-3-isobutylxanthine (0.1 mM) further stimulated this rate of glycerol release 3-fold. The neutral triglyceride lipase activity in cell-free preparations of differentiated cells was activated 105% by cyclic AMP-dependent protein kinase. Neutral cholesterol esterase, diglyceride lipase, and monoglyceride lipase were also activated (117%, 10%, and 37+, respectively) by cyclic AMP-dependent protein kinase. In contrast, protein kinase had no effect on any of the four lysosomal acid acylhydrolase activities. Thus, hormone-sensitive lipase, the most characteristic and functionally important enzyme of adipose tissue, has been characterized in differentiated 3T3-L1 cells. The 3T3-L1 cell should be a valuable model system in which to study regulation of hormone-sensitive lipase, particularly its long-term regulation.
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PMID:Hormone-sensitive lipase in differentiated 3T3-L1 cells and its activation by cyclic AMP-dependent protein kinase. 626 67

Although it has been documented that hormones promote lipolysis in the heart, an enzyme mediating this event has not been identified. We have found that perfusion of the rat heart with epinephrine, 3-isobutyl-1-methylxanthine, or dibutyryl (Bt2) cyclic AMP produced a biphasic effect on the activity of an enzyme having the properties of the intracellular fraction of lipoprotein lipase, i.e., stability in acetone:ether, pH optimum of 8.1, serum requirement, and sensitivity to heparin, NaCl, and protamine sulfate. We have termed this enzyme type L hormone-sensitive lipase (HSL). Perfusion with high concentrations of agent stimulate type L HSL activity, while perfusion with relatively low concentrations of agent inhibit enzyme activity. This inhibition is not observed if enzyme is extracted in organic solvent. The activity of type L HSL has a high negative (r greater than -0.93) relationship with the amount of triglyceride in the heart. Early attempts to purify this enzyme from control and epinephrine-stimulated hearts suggest that the enzyme can be obtained in two forms (control and activated). Although the data suggest that the mechanism of control of this enzyme is complex, it seems that the activity is controlled, in part, through cyclic AMP and protein kinase.
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PMID:Hormonal regulation of myocardial lipolysis. 631 45

Endogenous lipid droplets were prepared by subjecting fat cells to hypotonic shock and to Triton X-100 treatment. The structure of the endogenous lipid droplet fraction was examined by scanning and transmission electron microscopies. Neither intact fat cells nor disrupted cell membranes were detectable in the endogenous lipid droplet fraction. With this endogenous substrate, epinephrine elicited lipolysis with either hormone-sensitive lipase or lipoprotein lipase, but no cyclic AMP-protein kinase mediated stimulation of lipolysis was observed. On the other hand, epinephrine did not stimulate lipolysis when triolein emulsified with arabic gum was used as substrate. With the latter exogenous substrate, however, cyclic AMP-protein kinase was found to stimulate lipolysis with hormone-sensitive lipase as enzyme. These results agree with the proposal of Wise and Jungas that the epinephrine-stimulated increase of hydrolysis of endogenous fat is not mediated through cyclic AMP-protein kinase. A possible mechanism of hydrolysis of endogenous fat by induction of lipolysis by epinephrine in fat cells is discussed.
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PMID:Role of endogenous lipid droplets of fat cells in epinephrine-induced lipolysis. 684 55

In this review, we evaluate the relative regulatory importance of specific strategic enzymes (in particular glycogen synthase, acetyl-CoA carboxylase [ACC] and the pyruvate dehydrogenase complex [PDH]) for carbohydrate utilization as an anabolic precursor and as an energy substrate during the nutritional transitions between the fed and fasted states. The involvement of the specific protein kinases contributing to the inactivation of these enzymes by phosphorylation [cyclic AMP-dependent protein kinase, AMP-activated protein kinase and PDH kinase] in achieving each regulatory response is also assessed. We demonstrate a striking temporal correlation between hepatic glycogen mobilization and PDH and ACC inactivation by phosphorylation during the immediate postabsorptive period; in contrast, rates of hepatic glycogen synthesis and PDH and ACC expressed activities do not change in parallel during refeeding. The results are consistent with shifting of the primary sites of control for overall hepatic carbon flux during the fed-to-starved and starved-to-fed nutritional transitions achieved, at least in part, by a complex pattern of regulation by protein phosphorylation and metabolites which is critically dependent on the precise nutritional status. Data are also presented that demonstrate asynchronous suppression of glucose uptake/phosphorylation and pyruvate oxidation in cardiac and skeletal muscle during progressive starvation. Analogous asynchrony is observed in the reactivation of these processes in cardiac and skeletal muscle during refeeding after starvation. We provide evidence in support of the concept that selective suppression of pyruvate oxidation in oxidative muscles during early starvation and during the initial phase of refeeding is achieved because of differential sensitivity of glucose uptake/phosphorylation and pyruvate oxidation to lipid-fuel utilization. We discuss the relative importance of regulatory events governing local fatty acid production and utilization (via lipoprotein lipase and carnitine palmitoyltransferase 1, respectively) or overall fatty acid supply (dictated by events at the adipocyte) for fuel utilization by muscle during nutritional transitions. Finally, we assess the regulatory importance of glycogen synthesis in determining overall rates of glucose clearance by skeletal muscle during alimentary hyperglycemia and hyperinsulinemia.
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PMID:Mechanisms involved in the coordinate regulation of strategic enzymes of glucose metabolism. 810 32

GH has been previously shown in Ob1771 adipose cells to activate transiently the expression of c-fos gene by a protein kinase-C-dependent pathway and to modulate, at last in part by a protein kinase-C-dependent pathway, the expression of the lipoprotein lipase (LPL) gene. In Ob1771 cells exposed to GH, under conditions where protein synthesis is inhibited by cycloheximide, the modulation of LPL gene expression is prevented, suggesting that synthesis of trans-acting factor(s) is required to modulate LPL gene expression. The present results indicate the involvement of c-Fos protein in this modulation; this involvement is supported by various lines of evidence: 1) upon GH stimulation, the increase in c-fos mRNA content is followed by the emergence of c-Fos protein within the nucleus, and this emergence precedes the increase in LPL mRNA content; 2) in GH-treated Ob1771 cells, exposure to antisense sof oligonucleotides abolishes the synthesis of c-Fos protein; and 3) at the same time, the increase in LPL mRNA content and LPL activity does not occur, whereas sense fos oligonucleotides show no effect. It is concluded that c-Fos protein plays an intermediary role in the modulation of LPL gene expression by GH.
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PMID:The regulation by growth hormone of lipoprotein lipase gene expression is mediated by c-fos protooncogene. 841 45

Mechanisms of the stimulatory release of lipoprotein lipase (LPL) activity from isolated rat fat pads by sodium orthovanadate (vanadate) were studied through a cAMP-dependent process. A potent inhibitor of insulin receptor tyrosine kinase, quercetin, inhibited the vanadate-increasing effect on the LPL activity in fat pads, but did not inhibit the vanadate-stimulated release of LPL activity from the fat pads. Propranolol and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) decreased the vanadate-stimulated release in a dose-dependent manner. Isoproterenol and dibutyryl cAMP (Bt2cAMP) stimulated the release of LPL activity from fat pads. Vanadate, as well as isoproterenol, rapidly increased the cAMP content in fat pads, and this increase was almost completely inhibited by propranolol. Vanadate increased the cAMP-dependent protein kinase (PKA) activity ratios calculated from the measurement in the presence or absence of cAMP or PKa inhibitor. These results suggest that the vanadate-stimulated release of LPL activity is associated with a process involving a rapid increase in the cAMP content accompanied by the activation of PKA.
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PMID:Involvement of the rapid increase in cAMP content in the vanadate-stimulated release of lipoprotein lipase activity from rat fat pads. 895 Nov 55

HSL from chicken adipose tissue exhibits remarkable activation upon phosphorylation with cAMP-dependent protein kinase (cAMP-PK) compared to HSL from rat and human adipose tissue. In order to characterize the chicken HSL enzyme, it was purified 3500 fold from a chicken adipose tissue homogenate using pH 5.2 precipitation and anion-exchange chromatography. The purified chicken HSL was identified as an 86 kDa protein using Western blot analysis. The HSL diacylglycerol lipase activity was inhibited by 98% upon incubation with anti-rat HSL antiserum, and the specific activity of chicken HSL was estimated to be approximately the same as for the rat enzyme. Furthermore, the 86 kDa polypeptide was phosphorylated by cAMP-PK to about the same stoichiometry as for the recombinant rat enzyme. Hence, our results demonstrate that HSL from chicken adipose tissue is comparable in size and specific activity to HSL from mammalian species, and not a smaller 42 kDa polypeptide with 1000-fold lower specific activity as previously reported (Berglund, L., Khoo, J. C., Jensen, D., and Steinberg, D., 1980 J. Biol. Chem. 255, 5420-5428).
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PMID:Partial purification and identification of hormone-sensitive lipase from chicken adipose tissue. 922 33


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