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)

In rat adipocytes hormone-sensitive lipase is phosphorylated at two sites termed 'regulatory' and 'basal', in the former case by cyclic AMP-dependent protein kinase causing an activation of the lipase [(1984) Proc. Natl. Acad. Sci. USA 81, 3317-3321]. Here, the basal phosphorylation site was found to be phosphorylated by glycogen synthase kinase-4 without any effects on lipase activity, or on the extent of its activation subsequent to phosphorylation of the regulatory site. Glycogen synthase kinase-3, casein kinase-I, and casein kinase-II did not phosphorylate the lipase. Phosphorylase kinase phosphorylated it to a very low extent at a third phosphorylation site not phosphorylated in the fat cell.
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PMID:Phosphorylation of the basal site of hormone-sensitive lipase by glycogen synthase kinase-4. 302 14

Endogenous lipid droplets were prepared by subjecting fat cells to hypotonic shock and Triton X-100 treatment. The endogenous lipid droplets were found to show lipolysis in response to epinephrine, but not to show lipogenesis from glucose in response to insulin. These results indicated that the preparation of endogenous lipid droplets did not contain any intact fat cells capable of insulin-stimulated lipogenesis. Results with these endogenous lipid droplets showed that protein kinase inhibitor inhibited protein kinase-mediated hormone-sensitive lipase activity but did not reduce epinephrine-induced lipolysis. Cyclic AMP and dibutyryl cyclic AMP induced lipolytic activity in the presence of 80 mM KCl and their activities were not inhibited by protein kinase inhibitor. Phospholipase C inhibited epinephrine, cyclic AMP and dibutyryl cyclic AMP-induced lipolysis, but did not affect the lipolytic activity of either the activated or non-activated form of hormone-sensitive lipase. These results indicate the existence of a protein kinase inhibitor-insensitive and phospholipase C-sensitive lipolytic pathway in rat adipocytes.
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PMID:Studies on a protein kinase inhibitor-insensitive, phospholipase C-sensitive pathway of lipolysis in rat adipocytes. 302 21

Adipocytes from spontaneously hypertensive rats demonstrated a blunted lipolytic response to isoproterenol and dibutyryl cyclic AMP. (-)-[3H]Dihydroalprenolol binding was examined in adipocytes from normotensive and spontaneously hypertensive rats. Increasing concentrations of isoproterenol decreased total (-)-[3H]dihydroalprenolol binding to intact cells from normotensive rats, and the efficacy of competition was decreased in adipocytes from spontaneously hypertensive rats. Scatchard analysis indicated that the number of (-)-[3H]dihydroalprenolol binding sites and the affinity of dihydroalprenolol binding were comparable between normotensive and spontaneously hypertensive rats. Isoproterenol- and Gpp(NH)p-stimulated adenylate cyclase activity was consistently depressed in adipocyte membranes from spontaneously hypertensive rats as compared to normotensive rats. No difference in fluoride-stimulated adenylate cyclase activity was observed. The blunted lipolytic and cyclic AMP response to isoproterenol in these cells suggest a postreceptor lesion of the lipolytic pathway (possibly the guanine nucleotide regulatory protein) in adipocytes from spontaneously hypertensive rats. The blunted lipolytic response to dibutyryl cyclic AMP suggests defective regulation of lipolytic enzymes at the protein kinase-hormone-sensitive lipase level.
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PMID:Lipolysis and beta-adrenergic receptor binding on adipocytes of spontaneously hypertensive rats. 303 23

Long-chain fatty acid esters of 17 beta-estradiol and other steroid hormones, which are formed in hormone-sensitive tissues, can be regenerated to the free hormone by the action of an esterase present in the cytosol. This esterase has now been examined in bovine placenta cotyledons. Activity towards steroid fatty acid esters was accompanied by activity towards a diacylglycerol analogue and cholesteryl oleate. During purification procedures, the ratio of activities towards the diacylglycerol analogue and estradiol 17 beta-oleate remained approximately constant. Activity towards these two substrates was inhibited by increasing concentrations of HgCl2 and phenylmethanesulfonyl fluoride in a parallel manner. Upon treatment with [3H]diisopropyl fluorophosphate, a major labelled species of Mr approx. 84,000 was formed. Activation by ATP and the catalytic subunit of cAMP-dependent protein kinase occurred. These properties were very similar to those of the hormone-sensitive lipase of bovine adipose tissue previously reported and run in parallel in this study. A highly purified preparation of this latter enzyme was found to hydrolyse steroid fatty acid esters and relative activities towards such substrates, diacylglycerol analogue and cholesteryl oleate, were similar to the placenta esterase. When the two esterases were phosphorylated with [gamma-32P]ATP, a labelled species of Mr 84,000 was isolated in both cases by use of an antibody raised against purified hormone-sensitive lipase of bovine adipose tissue. It is concluded that hormone-sensitive lipase is very likely the enzyme responsible for hydrolysis of steroid fatty acid esters in bovine placenta and possibly steroid hormone target tissues in general.
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PMID:Hormone-sensitive lipase is involved in the hydrolysis of lipoidal derivatives of estrogens and other steroid hormones. 319 30

The primary structure of a region on hormone-sensitive lipase was determined to be: Lys-Thr-Glu-Pro-Met-Arg-Arg-Ser- Val-Ser-Glu-Ala-Ala-Leu-Thr-Gln-Pro-Glu-Gly-Pro-Leu-Gly-Thr-Asp-Ser-Leu-Lys. Ser-8 was the only residue in the intact protein phosphorylated by cyclic AMP-dependent protein kinase. However, Ser-10 also appeared to be present in a phosphorylated form, suggesting that it is a target for a distinct protein kinase in vivo.
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PMID:Primary structure of the site on bovine hormone-sensitive lipase phosphorylated by cyclic AMP-dependent protein kinase. 334 39

The effect of halothane on isoproterenol-stimulated lipolysis was determined in isolated rat epididymal fat cells. The maximal lipolytic response (Emax) activated by isoproterenol was 350 +/- 61 nmol of glycerol/10(5) cells/hr with an EC50 of 5.1 X 10(-9) M. When the adipocytes were simultaneously bubbled with 2.5% halothane, the Emax decreased to 158 +/- 43 nmol of glycerol/10(5) cells/hr and the dose response curve for isoproterenol was shifted to the right (EC50 3.5 X 10(-8) M, p less than 0.05). When lipolysis was maximally stimulated with (-)-isoproterenol (10(-6)M), the inhibitory effect of halothane was found to be both dose dependent (IC50 approximately 2.5%, v/v) and reversible following washout. Neither the nonhydrolyzable cAMP analog, 8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate (2 X 10(-3)M), nor forskolin (10(-6) M) was able to normalize lipolysis in the presence of halothane. The activation of cAMP-dependent protein kinase (EC 2.7.1.37) activity by isoproterenol was not different in halothane-exposed cells when compared to unexposed cells. When control adipocytes were exposed to isoproterenol (10(-6) M), there was a 2.5-fold increase in the activity of hormone-sensitive lipase (EC 3.1.1.3) from 0.64 +/- 0.13 to 1.53 +/- 0.32 pkat (pmol/sec) per mg (p less than 0.005, n = 10). However, in the presence of halothane (2.5%, v/v) isoproterenol stimulation of hormone-sensitive lipase was attenuated by 50% to values of 1.06 +/- 0.23 pkat/mg (p less than 0.01, n = 10). Halothane had no direct inhibitory effect on hormone-sensitive lipase since this enzyme's activity was unaffected when homogenates of isoproterenol-stimulated control cells were incubated with halothane. These studies suggest that halothane impairs the activation of hormone-sensitive lipase by cAMP-dependent protein kinase and in this manner inhibits beta-adrenergic-stimulated lipolysis.
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PMID:Mechanism of halothane-induced inhibition of isoproterenol-stimulated lipolysis in isolated rat adipocytes. 335 97

Brief incubation of partially purified preparations of hormone-sensitive lipase from rat epididymal fat pads with ATP, Mg(++), cyclic adenosine 3':5'-monophosphate and rabbit muscle protein kinase (phosphorylase b kinase kinase) resulted in enhancement of lipolytic activity (44-93%). Little or no activation was observed when either the cofactor mixture or the protein kinase was omitted. When the fat pads were incubated with epinephrine prior to homogenization, addition of kinase and cofactors to the soluble supernatant fraction caused no activation whereas good activation was obtained in preparations from paired fat pads not exposed to epinephrine. The results indicate that the cyclic AMP-mediated activation of hormone-sensitive lipase in adipose tissue involves a protein phosphorylation step. Whether the lipase itself is phosphorylated and thus activated or whether the protein kinase is activating a mediating enzyme, in analogy with its action in the glycogen phosphorylase system, remains to be determined.
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PMID:ATP-dependent and cyclic AMP-dependent activation of rat adipose tissue lipase by protein kinase from rabbit skeletal muscle. 431 80

A partially purified hormone-sensitive triglyceride lipase of human adipose tissue was found to be activated twofold by the addition of cyclic 3',5'-AMP, ATP, and magnesium ions. Lipase activities against diolein and monoolein were not affected. Addition of protein kinase inhibitor at zero time completely inhibited activation, and this inhibition was prevented by prior addition of an excess of exogenous protein kinase (from rabbit skeletal muscle). Addition of protein kinase inhibitor during the activation step blocked the activation process without a time lag, suggesting that protein kinase operates directly on hormone-sensitive lipase. Further purification yielded a fraction free of protein kinase, and lipase activation in this fraction depended absolutely on addition of exogenous kinase. Incubation of human fat with epinephrine or isoproterenol stimulated lipolysis and caused conversion of nonactivated hormone-sensitive lipase to its activated form, as indicated by a decrease in the activation subsequently obtainable in fractions prepared from such hormone-treated tissues. These findings strongly suggest that the stimulation of lipolysis by hormonal treatment is the consequence of the activation of hormone-sensitive triglyceride lipase by cyclic 3',5'-AMP-dependent protein kinase.
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PMID:The mechanism of activation of hormone-sensitive lipase in human adipose tissue. 436 Aug 57

3T3-L1 cells have been a useful model system for studying adipocyte differentiation and metabolism. They acquire a hormone-sensitive lipase during differentiation (Kawamura, M., et al. 1981. Proc. Natl. Acad. Sci. USA. 78: 732-735). In the present study the control of lipolysis in these cells was investigated. Basal glycerol release from cell monolayers was 437 nmol/mg protein per hr, and could be stimulated approximately 6-fold by exposure to 1 microM isoproterenol. Subcellular fractionation of stimulated cells revealed a redistribution of triglyceride lipase activity: loss from the infranatant fraction and increase in the pellet fraction. The redistribution was dosage-dependent and reversible. Treatment of intact cells with 8-bromoadenosine 3':5' cyclic monophosphate elicited similar redistribution of the lipase activity; however, disruption and incubation of untreated cells in the presence of ATP and either cyclic AMP or the catalytic subunit from cAMP-dependent protein kinase did not. The lipase activity in the pellet fraction was increased 3- to 4-fold after maximal lipolytic stimulation of intact cells, whereas phosphorylation of the enzyme in vitro yielded 1.4- to 1.6-fold stimulation in all subcellular fractions from untreated cells. The lipase found in the particulate fraction has the same properties as the previously characterized infranatant enzyme. It is suggested that interaction of the lipase with substrate and associated intracellular membranes may be a novel feature of the regulation of lipolysis.
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PMID:Lipolytic stimulation modulates the subcellular distribution of hormone-sensitive lipase in 3T3-L1 cells. 620 54

Hormone-sensitive lipase of rat adipose tissue was partially purified. The enzyme retained its capacity to be activated by cyclic AMP-dependent protein kinase throughout purification. When the partially purified 32P-labeled preparation was subjected to two-dimensional gel electrophoresis, the enzyme activity was found to be associated with a 32P-labeled protein of molecular weight 84 000. The result suggests that this 32P-labeled protein represents hormone-sensitive lipase or the catalytic subunit of the enzyme.
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PMID:Hormone-sensitive lipase of rat adipose tissue: correlation of activity with a protein of molecular weight 84 000. 625 Jun 30


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