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:2.7.11.11 (AMPK)
12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevation of cyclic AMP (cAMP) content in perfused rat hearts by exposure to glucagon, forskolin, and 1-methyl-3-isobutylxanthine (IBMX) increased rates of protein synthesis during the second hour of perfusion with buffer that contained glucose in the absence of added insulin. When tetrodotoxin was added to arrest contractile activity, glucagon, forskolin, and IBMX still elevated cAMP content and rates of protein synthesis. Perfusion of beating rat hearts at elevated aortic pressure (120 mm Hg vs. 60 mm Hg) also accelerated rates of protein synthesis and raised cAMP content and cAMP-dependent protein kinase activity during the second hour of perfusion. Insulin accelerated rates of protein synthesis in beating hearts during the first and second hour of perfusion but did not increase cAMP content. Elevation of aortic pressure in insulin-treated hearts raised cAMP content but had no further effect on rates of protein synthesis. Perfusion of arrested hearts for as little as 2 minutes at 120 mm Hg resulted in a rapid and sustained increase in cAMP content, cAMP-dependent protein kinase activity, and rate of protein synthesis after 60-120 minutes of additional perfusion at 60 mm Hg. Exposure of arrested hearts to 0.2 mM methacholine, a muscarinic-cholinergic agonist, for 5 minutes before elevation of perfusion pressure blocked the pressure-induced increases in cAMP content, cAMP-dependent protein kinase activity, and rates of protein synthesis. When hearts were removed from pertussis toxin-treated animals, methacholine did not block the effects of forskolin on these same three parameters. These studies indicated that elevation of tissue cAMP by hormone binding, direct activation of adenylate cyclase, or inhibition of phosphodiesterase resulted in acceleration of protein synthesis. Furthermore, the effects of increased aortic pressure to accelerate synthesis appeared to involve a cAMP-dependent mechanism that was independent of changes in contractile activity but could be blocked with a muscarinic-cholinergic agonist. Acceleration of protein synthesis by insulin was not associated with an elevation of cAMP.
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PMID:Increased cyclic AMP content accelerates protein synthesis in rat heart. 247 73

We have previously reported that the increase in glycogen synthase activity in human muscle during a euglycemic clamp was not associated with a measured increase in glycogen synthase phosphatase activity after a 200-min insulin administration. To investigate further the mechanism of the regulation of human muscle glycogen synthase by insulin, we measured the activity of cAMP-dependent protein kinase before and after a 200-min hyperinsulinemic euglycemic clamp in Southwest American Indians. Insulin infusion resulted in a decreased cAMP-dependent protein kinase activity assayed at physiological cAMP concentration with increased glycogen synthase activity in all subjects (n = 5; P less than 0.01). No significant change was observed in cAMP-independent protein kinase activity. These results suggest that 200 min of insulin administration during a euglycemic clamp may regulate human muscle glycogen synthase activity by mechanisms other than the stimulation of phosphatase; one probable mechanism is by decreasing the activity of cAMP-dependent protein kinase.
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PMID:Adenosine 3',5'-monophosphate-dependent protein kinase activity decreases in human muscle after insulin infusion. 250 13

Activation of glycolysis by insulin in cultured rat hepatocytes is preceded by an activation of phosphofructokinase 2 (PFK 2) and subsequent rise of the fructose 2,6-bisphosphate [Fru(2,6)P2] level. Extracellular addition of ATP or puromycin prevented the hormonal effect on glycolysis. The mechanism through which the purines abolished glycolytic stimulation was investigated. 1. 50 microM ATP completely prevented the 3-5-fold insulin-dependent increase of glycolysis, irrespective of whether the cells initially possessed a low or a high Fru(2,6)P2 content. 50 microM puromycin prevented the stimulation of glycolysis by insulin only in cells whose initial Fru(2,6)P2 levels were low and had to be increased by insulin prior to the increase in glycolysis. It did not antagonize the action of insulin cells with initial high Fru(2,6)P2 content. 2. ATP exerted effects on its own; it decreased initially high Fru(2,6)P2 levels by 95% within 10 min and decreased the basal glycolytic rate by 60%. Half-maximal effects on the Fru(2,6)P2 level were obtained with about 25 microM ATP or 15 microM adenosine 5'[beta, gamma-methylene]triphosphate. ADP and adenosine-5-[gamma-thio]triphosphate were as effective as ATP, whereas 100 microM adenosine 5'[alpha, beta-methylene]triphosphate elicited no effect. Puromycin neither decreased high Fru(2,6)P2 levels nor inhibited basal glycolysis. 3. Extracellular ATP (100 microM) led to inhibition of the active form of PFK 2. Intracellular levels of Glc6P, citrate, ATP, ADP and AMP were increased by extracellular ATP, the phosphoenolpyruvate content was decreased, Fru6P and glycerol 3-phosphate levels stayed constant. Puromycin did not inhibit PFK 2. 4. Both puromycin and ATP prevented the insulin-dependent rise of the Fru(2,6)P2 level, they abolished the activation of PFK 2 by the hormone. Puromycin did not block the accumulation of Fru(2,6)P2 provoked by glucose addition; ATP also antagonized the glucose-dependent increase. 5. 100 microM ATP elevated the cAMP-dependent protein kinase activity ratio from 0.1 to 0.38 and increased the level of inositol trisphosphate by 16-fold within 5 min, whereas puromycin was without effect on either level. It is concluded that the two purines block the insulin effect on glycolysis by preventing the hormone increasing the Fru(2,6)P2 level. The mode of action, however, seems to be different: ATP antagonizes insulin action in that it leads to increased inhibition of PFK 2 whereas puromycin prevents the activation of PFK 2 by insulin.
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PMID:Stimulation by insulin of glycolysis in cultured hepatocytes is attenuated by extracellular ATP and puromycin through purine-dependent inhibition of phosphofructokinase 2 activation. 252 68

The time-courses of isoproterenol activation of rat adipocyte particulate low Km cAMP phosphodiesterase (PDE) activity, cAMP-dependent protein kinase (A-kinase), and glycerol production were measured in the presence and absence of insulin. Isoproterenol (100 nM) alone rapidly activated A-kinase 8- to 10-fold and increased particulate cAMP PDE by approximately 100%. A-kinase and PDE activity remained relatively constant for at least 25 to 30 min. Kact values for isoproterenol activation of PDE and lipolysis were similar. In comparison with isoproterenol, insulin (0.1-0.3 nM) alone increased particulate cAMP PDE at a slower rate and to a lesser extent (by approximately 50% within 12 to 16 min) and without any change in A-kinase. With insulin plus isoproterenol there was a rapid, transient, and synergistic activation of particulate cAMP PDE, which temporally correlated with a decrease in A-kinase and reduction in lipolysis. These and other data suggest the following: 1) there is a close concentration-dependent and temporal relationship in isoproterenol activation of adenylate cyclase, of A-kinase, and of particulate cAMP PDE; 2) isoproterenol and insulin activate particulate cAMP PDE by two distinct mechanisms; 3) the temporal changes in PDE and A-kinase in the presence of insulin and isoproterenol suggest that insulin activation of the PDE does not require, but may be enhanced by, elevated cAMP and is important in the antilipolytic action of insulin.
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PMID:Role of hormone-sensitive low Km cAMP phosphodiesterase in regulation of cAMP-dependent protein kinase and lipolysis in rat adipocytes. 253 13

Addition of protein kinase C activators to electropermeabilized frog rod photoreceptors enhances the phosphorylation of proteins with molecular masses of 54, 24, 19, 17, 12, and 11 kDa. The latter two correspond to components I and II, which are also phosphorylated by cyclic nucleotide-dependent protein kinase. Stimulation of phosphorylation by the protein kinase C activator oleoylacetylglycerol (OAG) is half-maximal at 7.7 microM OAG and is reduced by the protein kinase C inhibitor H-7. In contrast with earlier observations, no effects of calcium, calmodulin, or insulin on protein phosphorylations are observed. We find evidence for only three protein kinases in rod outer segments: a protein kinase C-like activity, cAMP-dependent protein kinase, and rhodopsin kinase. With the exception of components I and II, the substrate proteins for each kinase are distinct. Treatment of intact rods with OAG decreases the amplitude of the photoresponse and dark levels of cGMP up to 40%, as well as depressing the light-stimulated decrease in cGMP levels. These effects are observed between 0.1 and 1 microM OAG. The data suggest that OAG-sensitive reactions may modulate pathways that support the light response.
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PMID:Stimulation of protein phosphorylations in frog rod outer segments by protein kinase activators. Suppression of light-induced changes in membrane current and cGMP by protein kinase C activators. 254 93

Insulin treatment of HeLa S3 cells activates an S6-phosphorylating protein kinase. Although this enzyme has chromatographic properties resembling those of described proteolytic fragments of other protein kinases, namely protein kinase C, protease-activated kinase II and histone-4 protein kinase, and although insulin has been proposed by others to cause S6 phosphorylation via proteolytic protein kinase activation, the insulin-induced increase in S6-kinase activity described here is probably not due to proteolysis. Rather, the activity indicates the existence, in HeLa cells, of an interconvertible S6 kinase, since the insulin-induced activity increase was rapidly reversed under hyperthermic stress, and since this effect of hyperthermia was itself reversible. The S6-kinase activities from serum- and from insulin-stimulated HeLa cells resemble each other closely and are likely to represent the same enzyme. The enzyme may therefore mediate both signals delivered by mitogens and the insulin signal. Analysed at an in vitro transfer of 1 mol phosphate/mol S6, this S6 kinase activity does not phosphorylate the (principal) S6 site recognized by the cAMP-dependent protein kinase.
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PMID:Insulin-induced S6 kinase activation in HeLa cells and its reversal by hyperthermic stress. 254 5

We have examined the acute effects of insulin and isoproterenol on the phosphorylation state of the insulin-regulatable glucose transporter (IRGT) in rat adipocytes. The IRGT was immunoprecipitated from either detergent-solubilized whole-cell homogenates or subcellular fractions of 32P-labeled fat cells and subjected to sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The 32P-labeled IRGT was detected by autoradiography as a species of apparent Mr 46,000. Insulin stimulated translocation of the IRGT from low-density microsomes to the plasma membrane but did not affect phosphorylation of the transporter in either fraction. Isoproterenol inhibited insulin-stimulated glucose transport by 40% but was without effect on the subcellular distribution of the transporter in either the presence or absence of insulin. Isoproterenol stimulated phosphorylation of the IRGT 2-fold. Incubating cells with dibutyryl-cAMP and 8-bromo-cAMP also stimulated phosphorylation 2-fold, and the transporter was phosphorylated in vitro when IRGT-enriched vesicles were incubated with cAMP-dependent protein kinase and [gamma-32P]ATP. These results suggest that isoproterenol stimulates phosphorylation of the IRGT via a cAMP-dependent pathway and that phosphorylation of the transporter may modulate its ability to transport glucose.
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PMID:Isoproterenol stimulates phosphorylation of the insulin-regulatable glucose transporter in rat adipocytes. 255 13

A monoclonal antibody was prepared against the regulatory subunit (RII) of rat liver type II cAMP-dependent protein kinase. Autophosphorylated and nonphosphorylated RII in extracts from rat liver or hepatocytes were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and quantified by immunoblot analysis with this antibody. Under basal conditions, 90% of hepatocyte RII was in the phosphorylated form. Incubating hepatocytes with 8-bromo-cAMP and a phosphodiesterase inhibitor resulted in activation of cAMP-dependent protein kinase and glycogenolysis but did not affect phospho RII levels. RII phosphorylation was also unaffected by the inclusion of sufficient insulin to cause a decrease in cAMP-dependent protein kinase activity and glycogenolysis. The results indicate that unlike other cell types, dissociation of rat hepatocyte type II cAMP-dependent protein kinase does not result in dephosphorylation of RII. The biochemical basis for the apparent lack of RII dephosphorylation in intact hepatocytes was examined by comparison with smooth muscle where RII is rapidly dephosphorylated. Rat liver extract contained 4-fold less RII and had an 80-fold lower rate of dephosphorylation of endogenous RII compared to bovine smooth muscle extract. The differences in the rates of RII dephosphorylation in tissue extracts were not observed using purified RII from either tissue. These data suggested that the slow rate of RII dephosphorylation in rat hepatocytes is due to a difference in the susceptibility of endogenous rat liver RII to dephosphorylation rather than a difference in phosphatase activity.
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PMID:Autophosphorylation of rat liver type II cAMP-dependent protein kinase. 255 4

Insulin decreases multifunctional protein kinase (MFPK) activity in rat adipose tissue [Ramakrishna, S., & Benjamin, W. B. (1988) J. Biol. Chem. 263, 12677-12681]. Insulin also decreases the phosphorylation of peptide B but increases the phosphorylation of peptide A of ATP-citrate lyase (ATP-CL). The mechanism for this increase in peptide A phosphorylation was studied with purified ATP-CL from control and insulin- and isoproterenol-treated fat pads by using MFPK and the catalytic subunit of cAMP-dependent protein kinase (A-kinase). ATP-CL purified from insulin-treated fat pads is a better substrate for phosphorylation by MFPK compared to controls. This result is consistent with the hypothesis that insulin action decreases peptide B phosphorylation. To determine if the degree of phosphorylation at peptide B affects the phosphorylation rate of peptide A by A-kinase, ATP-CL was prepared with determined phosphate contents of peptides A and B. ATP-CL with a low phosphate content at peptide B is a better substrate for phosphorylation at peptide A by A-kinase than is ATP-CL with a high phosphate content at peptide B. These results suggest that the insulin-induced increase in ATP-CL phosphorylation at peptide A is due to a decrease in peptide B phosphorylation. ATP-CL prepared from isoproterenol-treated fat pads is also a better substrate for phosphorylation at peptide B by MFPK than controls. This increase in phosphorylation at peptide B by MFPK is due to positive second-site regulation by the isoproterenol-induced increase in peptide A phosphorylation.
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PMID:Effect of insulin on ATP-citrate lyase phosphorylation: regulation of peptide A and peptide B phosphorylations. 265 30

The endogenous inhibitor of cAMP-dependent protein kinase (PKI) in chick kidney is regulated by the vitamin D status of the animal. To determine the specific factors that are involved in the regulation of chick kidney PKI, chicks were raised on a low (0.05%), normal (1%), or high (3%) calcium diet and given vitamin D3 or vehicle three times a week orally. The results from this experimental protocol show that vitamin D3 or one or more of its metabolites and serum calcium levels are both involved in the regulation of chick kidney PKI in vivo. Measurement of PKI activity in primary cultures of chick kidney cells revealed treatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3) led to a 90-95% decrease in PKI activity. This effect of 1,25-(OH)2D3 was dose dependent, and neither PTH nor insulin was able to reverse it completely. Treatment with PTH caused 30-60% increase in PKI activity, and cell cultures that were grown in medium containing either 0.5 or 2 mM calcium chloride had similar PKI activities. Taken together, these results indicate that 1,25-(OH)2D3, the most physiologically active form of vitamin D3, is the predominant regulator of PKI, but serum calcium, indirectly through the regulation of PTH secretion, is also involved.
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PMID:Hormonal regulation of chick kidney inhibitor of adenosine 3',5'-monophosphate-dependent protein kinase. 265 46


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