Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of fasting on phosphotyrosine phosphatase (PTPase) activities in particulate (PF) and cytosolic (CF) fractions of rat adipocytes and liver. PTPase activity was assessed using [32P]tyrosine insulin receptor (IR). In adipocytes, 48 h fasting significantly inhibited PTPase activity. Dephosphorylation of IR by PF and CF PTPases was reduced by 80 and 65%, respectively. Similar reductions of lesser magnitude were observed in fasted rat livers. The effect of fasting was completely reversed by either refeeding or by incubating "fasted" adipocytes for 2 h in tissue culture medium containing 5 mM glucose. Neither 20 mM glucose nor the presence of insulin influenced phosphatase activity. Because fasting is accompanied by elevated protein kinase C (PKC) and adenosine 3',5'-cyclic monophosphate (cAMP) levels, we examined their influence on adipocyte PTPases. Neither activation (1 microM 12-O-tetradecanoylphorbol-13-acetate) nor inhibition (20 microM sphingosine) of PKC affected PTPase activity. In contrast, cAMP (2 mM) significantly inhibited PTPase activity (80% inhibition at 2 h), and its effect was prevented by a cAMP antagonist RpcAMP. Fasting- and cAMP-induced inhibition of PTPase activity was restored by incubating PF with trypsin (4 micrograms/ml for 5 min), which separated the putative inhibitors from the phosphatases. We conclude that fasting-induced inhibition of PTPases is mediated by elevated cAMP levels, most likely by activating phosphatase inhibitors.
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PMID:Role of cAMP in mediating effects of fasting on dephosphorylation of insulin receptor. 131 6

Fructose-1,6-diphosphate (FDP) is a physiological product which exhibits pharmacological properties. This study shows that FDP (1-3 mM) inhibits platelet aggregation induced by the agonists thrombin, vasopressin, platelet activating factor, ADP, adrenaline, arachidonate and the stable thromboxane analogue U 44069. Thrombin-promoted ATP secretion and cytosolic Ca2+ rise are also drastically inhibited by FDP, which decreases, although to a lesser extent, the protein kinase C-dependent phosphorylation of the 47 kDa protein. The inhibition on thrombin-induced aggregation is shared, albeit less efficiently, by glucose-1,6-diphosphate and fructose-2,6-diphosphate but not by other phosphorylated monosaccharides (fructose-1:2 cyclic,6-diphosphate, glucose-1- and glucose-6-phosphate, fructose-1- and fructose-6-phosphate, mannose-6-phosphate and 5-phosphoryl ribose-1-pyrophosphate). FDP does not affect platelet activation induced by the protein kinase C activators dioctanoylglycerol or phorbol 12-myristate 13-acetate. No increase of cAMP concentration is observed in FDP-treated platelets. Altogether, these results indicate that FDP inhibits platelet activation at a level preceding phospholipase C. The data are consistent with a general inhibitory action of FDP on signal transmission.
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PMID:Fructose-1,6-diphosphate inhibits platelet activation. 131 5

A potential role of arachidonic acid in the modulation of insulin secretion was investigated by measuring its effects on calmodulin-dependent protein kinase and protein kinase C in islet subcellular fractions. The results were interpreted in the light of arachidonic acid effects on insulin secretion from intact islets. Arachidonic acid could replace phosphatidylserine in activation of cytosolic protein kinase C (K0.5 of 10 microM) and maximum activation was observed at 50 microM arachidonate. Arachidonic acid did not affect the Ca2+ requirement of the phosphatidylserine-stimulated activity. Arachidonic acid (200 microM) inhibited (greater than 90%) calmodulin-dependent protein kinase activity (K0.5 = 50-100 microM) but modestly increased basal phosphorylation activity (no added calcium or calmodulin). Arachidonic acid inhibited glucose-sensitive insulin secretion from islets (K0.5 = 24 microM) measured in static secretion assays. Maximum inhibition (approximately 70%) was achieved at 50-100 microM arachidonic acid. Basal insulin secretion (3 mM glucose) was modestly stimulated by 100 microM arachidonic acid but in a non-saturable manner. In perifusion secretion studies, arachidonic acid (20 microM) had no effect on the first phase of glucose-induced secretion but nearly completely suppressed second phase secretion. At basal glucose (4 mM), arachidonic acid induced a modest but reproducible biphasic insulin secretion response which mimicked glucose-sensitive secretion. However, phosphorylation of an 80 kD protein substrate of protein kinase C was not increased when intact islets were incubated with arachidonic acid, suggesting that the small increases in insulin secretion seen with arachidonic acid were not mediated by protein kinase C. These data suggest that arachidonic acid generated by exposure of islets to glucose may influence insulin secretion by inhibiting the activity of calmodulin-dependent protein kinase but probably has little effect on protein kinase C activity.
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PMID:Parallel effects of arachidonic acid on insulin secretion, calmodulin-dependent protein kinase activity and protein kinase C activity in pancreatic islets. 131 20

To elucidate the acute effect of insulin on its receptor, rat adipocytes were preincubated with insulin, washed with KCN to inhibit receptor cycling, and 125I-labeled insulin binding was measured. Preincubating cells from young insulin-sensitive rats with insulin increased cell surface binding up to approximately fourfold without changing apparent receptor affinity. This effect was rapid (t1/2 less than 5 min) and had a similar dose-response relationship as the effect on glucose transport. It was also energy dependent because preincubation with KCN completely abolished the effect of subsequent insulin exposure. The increased binding capacity was not recovered after cell solubilization or in partially purified receptors or isolated plasma membranes. Cells pretreated with insulin were less sensitive to the ability of trypsin to remove cell surface receptors, suggesting a conformational change of the receptors. This was also supported by the finding that the polyclonal binding in insulin-treated but not in control cells. Vanadate mimicked the effect of insulin to increase insulin binding, whereas concanavalin A, vasopressin, phorbol esters, or the adenosine analogue phenyl isopropyl adenosine was without effect. Insulin-resistant adipocytes from obese rats displayed no increase in cell surface binding after insulin treatment, despite normal tyrosine kinase activity in response to insulin. Thus, both insulin and vanadate elicit a rapid effect to markedly increase the number of cell surface insulin binding sites in intact rat adipocytes. This appears to occur independently of protein kinase C and the inhibitory GTP binding protein (Gi). Furthermore, the effect of insulin could not be demonstrated in insulin-resistant cells, suggesting that this mechanism may be of importance for the regulation of insulin sensitivity.
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PMID:Insulin can rapidly increase cell surface insulin binding capacity in rat adipocytes. A novel mechanism related to insulin sensitivity. 131 56

The role of protein phosphatases in the regulation of insulin release from rat pancreatic islets was studied with protein phosphatase inhibitors, okadaic acid and calyculin A. Okadaic acid inhibited glucose- and glyceraldehyde-induced insulin release dose-dependently and also inhibited the potentiation of glucose-induced release either by adding forskolin, an activator of adenylate cyclase or by increasing K+ concentration to 25 mM. At a non-stimulatory concentration of 3 mM glucose, a high concentration (2 microM) of okadaic acid inhibited insulin release induced by high K+ or 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, but a low concentration (1 microM) of okadaic acid did not significantly inhibit TPA-induced insulin release. Calyculin A also inhibited glucose-induced insulin release, and the effect was greater than that of okadaic acid. The data suggest that protein phosphatases may play an important role in the regulation of insulin release.
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PMID:Effects of the protein phosphatase inhibitors okadaic acid and calyculin A on insulin release from rat pancreatic islets. 133 May 3

The effects of KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CamPKII), on insulin secretion and protein phosphorylation were studied in rat pancreatic islets and RINm5F cells. KN-62 was found to dose-dependently inhibit autophosphorylation of CamPKII in subcellular preparations of RINm5F cells (K0.5 = 3.1 +/- 0.3 microM), but had no effect on protein kinase C or myosin light chain kinase activity. KN-62, but not the inactive analogue KN-04, dose-dependently inhibited glucose-induced insulin release (K0.5 = 1.5 +/- 0.5 microM) in a manner similar to the inhibition of CamPKII autophosphorylation. KN-62 (10 microM) inhibited carbachol (in the presence of 8 mM glucose) and potassium-stimulated insulin secretion from islets by 53% and 59%, respectively. These results support a role of CamPKII in glucose-sensitive insulin secretion.
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PMID:Inhibition of insulin secretion by KN-62, a specific inhibitor of the multifunctional Ca2+/calmodulin-dependent protein kinase II. 133 87

Beta-adrenergic, alpha-1-adrenergic and glucagon stimulation of glucose release were compared between hepatocytes which were freshly isolated, incubated for 3 h in suspension or cultivated for 4 or 24 h in plastic culture flasks in the presence and absence of the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast to the absence of an isoproterenol effect in freshly isolated hepatocytes, an increased sensitivity of glucose liberation towards isoproterenol could be observed 4 h after the start of culture, whereas the beta-receptor number was not found to be increased before 24 h. TPA has no effect on isoproterenol-stimulated glucose release at all investigated conditions. The alpha-1-adrenergic responses tested by using the alpha-1-adrenergic agonist phenylephrine is blocked completely in freshly isolated hepatocytes preincubated with 10(-6) M TPA. However, after 3 h incubation of hepatocytes in suspension or in primary culture, TPA had no effect on phenylephrine-stimulated glucose release. The effect of 10(-9) M glucagon on glucose release from freshly isolated hepatocytes was not influenced by TPA, whereas after 90 and 180 min incubation a significant decrease could be observed. On the other hand, TPA inhibited stimulation of adenylate cyclase activity by glucagon concentrations of 10(-5) M in freshly isolated hepatocytes, but no effect was found in hepatocytes incubated for 3 h in suspension or maintained for 24 h in primary culture. The different TPA effects may be an expression of changes of the accessibility of protein kinase C to TPA caused by translocation and/or intracellular activation of this enzyme at the tested experimental conditions.
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PMID:Phorbol ester effects on hormonal responses in freshly isolated short-term incubated and cultured hepatocytes. 133 70

The concentration of fibroblast growth factor (FGF), which is found in cerebrospinal fluid (CSF), markedly increases after the start of feeding. Food intake was dose-dependently suppressed by picomole doses of FGF and facilitated by anti-FGF antibody. This suppression was caused by activation of protein kinase C in glucose-sensitive neurons in the lateral hypothalamus. In situ hybridization by use of cDNA showed that acidic (a)FGF was produced in ependymal cells. The ependymal cells released aFGF by responding to glucose increase in CSF after feeding. Released aFGF diffused into the brain parenchyma and was taken by neurons. Passive avoidance was significantly more reliable after aFGF infusion into CSF. Clamping cerebral arteries in the gerbil induced ischemia, which damaged neurons in the CA1 layer of the hippocampus. Pretreatment with aFGF prevented this damage. Thus, aFGF is not only the most potent substance yet found for the suppression of feeding, but it is also extremely effective as a neurotrophic and memory facilitating substance.
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PMID:A new brain glucosensor and its physiological significance. 137 Feb 49

We describe the identification and characterization of the BMH1 gene from the yeast Saccharomyces cerevisiae. The gene encodes a putative protein of 292 amino acids which is more than 50% identical with the bovine brain 14-3-3 protein and proteins isolated from sheep brain which are strong inhibitors of protein kinase C. Disruption mutants and strains with the BMH1 gene on multicopy plasmids have impaired growth on minimal medium with glucose as carbon source, i.e. a 30-50% increase in generation time. These observations suggest a regulatory function of the bmh1 protein. In contrast to strains with an intact or a disrupted BMH1 gene, strains with the BMH1 gene on multicopy plasmids hardly grew on media with acetate or glycerol as carbon source.
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PMID:Characterization of the yeast BMH1 gene encoding a putative protein homologous to mammalian protein kinase II activators and protein kinase C inhibitors. 137 90

Pancreatic islets are targets for PTH. The acute exposure of the islets to PTH results in a rise in their cytosolic calcium ([Ca2+]i). It also stimulates insulin secretion in a manner similar to that produced by phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC), suggesting that the hormone may stimulate the activity of this enzyme. The present study examined the effect of PTH (1-34) on both cytosolic and membrane bound PKC activity of pancreatic islets and compared it with that of glucose and TPA. In the basal state, PKC activity is predominantly found in the cytosol. Both PTH or high glucose concentration caused a significant increase in membrane-bound and total PKC activity, whereas cytosolic enzyme activity remained unchanged. The effects of these two agonists peaked at 5 min and declined thereafter. The effect of PTH on PKC activity was abolished by the PTH antagonist ([Tyr-34] bovine PTH (7-34) NH2). In contrast, TPA induced a rise in membrane-bound PKC activity with simultaneous decrease in cytosolic pool of PKC without a change in total PKC activity. Removal of calcium from the incubation media resulted in partial and significant loss of PTH-induced rise in membrane-bound PKC activity. The data demonstrated that 1) PTH stimulate PKC activity of pancreatic islets in a manner similar to that of glucose, 2) both of the agonists increases total PKC activity of islets and translocation of the enzyme activity to the membranes of the islets, and 3) the effect of PTH is mediated, in part, by its ability to augment calcium entry into the islets and is most likely receptor mediated.
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PMID:Parathyroid hormone activates protein kinase C of pancreatic islets. 139 33


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