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)

Insulin stimulates hexose transport and phosphorylation of the insulin receptor in monolayer cultures of intact 3T3-L1 adipocytes. To assess the phosphorylation state of the receptor in situ, cells were equilibrated with [32P]orthophosphate and then disrupted under denaturing conditions which preserved the phosphorylation state of the receptor established in the cell. The insulin receptor, isolated by lectin adsorption and two-dimensional nonreducing/reducing polyacrylamide gel electrophoresis, occurred as a single oligomeric species with an apparent alpha 2 beta 2 subunit composition. This oligomeric structure was not altered by treating cells with insulin. Only the beta-subunit of the receptor was phosphorylated; [32P]phosphoserine and [32P] phosphotyrosine were both identified in the beta-subunit from cells in the unstimulated state, but only [32P] phosphotyrosine increased in cells stimulated with insulin. Neither insulin-like growth factors I nor II stimulated insulin receptor beta-subunit phosphorylation, although both activated hexose transport. Upon the addition of insulin, [32P]orthophosphate incorporated into the beta-subunit increased 4.5-fold (7-fold with respect to [32P]tyrosine) and was complete within 1 min (t1/2 = 8 s). Following the removal of insulin from the monolayers, [32P]beta-subunit fell to the basal level (t1/2 = 2.5 min); there was no lag phase before either transition. The tyrosine protein kinase activity, measured in vitro with a model substrate, was higher with immunoaffinity-purified insulin receptor from insulin-stimulated cells than from cells in the basal state. Hexose transport rate, measured using 3-O-[methyl-14C]glucose, was half-maximally stimulated at 2 nM insulin. A 1-min latency period followed insulin addition, after which a 7-fold increase in the steady-state rate of hexose uptake was achieved within 5 min. Upon the removal of insulin, hexose transport continued at the stimulated steady-state rate for 2.5 min and then declined to the basal rate with a half-time of 8 min. These kinetic experiments in situ and protein kinase activity measurements in vitro support the hypothesis that beta-subunit phosphorylation is an intermediate step linking insulin binding to the increased glucose transport rate.
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PMID:Insulin-dependent phosphorylation of the insulin receptor-protein kinase and activation of glucose transport in 3T3-L1 adipocytes. 352 54

The immunoglobulin fraction of a polyclonal anti-insulin receptor antibody (B-10) derived from a patient with severe insulin resistance and acanthosis nigricans was tested for its ability to activate the protein kinase activity of the insulin receptor and to mimic insulin action in Chinese hamster ovary cells expressing either wild type or kinase-deficient human insulin receptors. This antiserum had previously been reported to be insulinmimetic without activating the insulin receptor protein tyrosine kinase. Antibody B-10 bound to both wild type and mutant human insulin receptors, but it induced receptor down-regulation and stimulated hexose transport and thymidine incorporation into DNA only in cells expressing the wild type receptor. Furthermore, this antibody activated the kinase activity of the wild type insulin receptor in intact cells and in vitro. It is likely, therefore, that the biological activities of antibody B-10, like those of insulin, depend upon the protein tyrosine kinase activity of the insulin receptor.
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PMID:Reevaluation of the evidence that an antibody to the insulin receptor is insulinmimetic without activating the protein tyrosine kinase activity of the receptor. 368 Feb 77

N-(6-Phenylhexyl)-5-chloro-1-naphthalenesulfonamide (SC-9) activated Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C). SC-9 acted as a substitute for phosphatidylserine, which is one of the endogenous factors in activating protein kinase C. SC-9 was also effective in regulating the physiological functions at the whole-cell level. For example, SC-9 stimulated hexose transport activity in mouse fibroblasts, a protein kinase C-regulated cellular function. Thus, SC-9 may be useful to study the molecular basis of the regulation of protein kinase C activity, and the biological significance of this enzyme.
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PMID:N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide is one of a new class of activators for Ca2+-activated, phospholipid-dependent protein kinase. 377 49

The intragastric administration of ethanol to fed rats caused in their liver, within about 1 h, a 20-fold decrease in the concentration of fructose 2,6-bisphosphate, an activation of fructose 2,6-bisphosphatase, an inactivation of phosphofructo-2-kinase but no change in the concentration of cyclic AMP. Incubation of isolated hepatocytes in the presence of ethanol caused a rapid increase in the concentration of sn-glycerol 3-phosphate and a slower and continuous decrease in the concentration of fructose 2,6-bisphosphate with no change in that of hexose 6-phosphates. There was also a relatively slow activation of fructose 2,6-bisphosphatase and inactivation of phosphofructo-2-kinase. Glycerol and acetaldehyde had effects similar to those of ethanol on the concentration of phosphoric esters in the isolated liver cells. 4-Methylpyrazole cancelled the effect of ethanol but reinforced those of acetaldehyde. High concentrations of glucose or of dihydroxyacetone caused an increase in the concentration of hexose 6-phosphates and counteracted the effect of ethanol to decrease the concentration of fructose 2,6-bisphosphate. As a rule, hexose 6-phosphates had a positive effect and sn-glycerol 3-phosphate had a negative effect on the concentration of fructose 2,6-bisphosphate in the liver, so that, at a given concentration of hexose 6-phosphates, there was an inverse relationship between the concentration of fructose 2,6-bisphosphate and that of sn-glycerol 3-phosphate. These effects could be explained by the ability of sn-glycerol 3-phosphate to inhibit phosphofructo-2-kinase and to counteract the inhibition of fructose 2,6-bisphosphatase by fructose 6-phosphate. sn-Glycerol 3-phosphate had also the property to accelerate the inactivation of phosphofructo-2-kinase by cyclic AMP-dependent protein kinase whereas fructose 2,6-bisphosphate had the opposite effect. The changes in the activity of phosphofructo-2-kinase and fructose 2,6-bisphosphatase appear therefore to be the result rather than the cause of the decrease in the concentration of fructose 2,6-bisphosphate.
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PMID:The mechanism by which ethanol decreases the concentration of fructose 2,6-bisphosphate in the liver. 608 71

When glucose was added to a suspension of Saccharomyces cerevisiae in stationary phase, it caused a transient increase in the concentration of cyclic AMP and a more persistent increase in the concentration of hexose 6-phosphate and of fructose 2,6-bisphosphate. These effects of glucose on cyclic AMP and fructose 2,6-bisphosphate but not that on hexose 6-phosphate were greatly decreased in the presence of 0.15 mM acridine orange or when a temperature-sensitive mutant deficient in adenylate cyclase was used at the restrictive temperature. Incubation of the cells in the presence of dinitrophenol and in the absence of glucose increased the concentration of both cyclic AMP and fructose 2,6-bisphosphate, but with a minimal change in that of hexose 6-phosphate. Glucose induced also in less than 3 min a severalfold increase in the activity of 6-phosphofructo-2-kinase and this effect was counteracted by the presence of acridine orange. When a cell-free extract of yeast in the stationary phase was incubated with ATP-Mg and cyclic AMP, there was a 10-fold activation of 6-phosphofructo-2-kinase. Finally, the latter enzyme was purified 150-fold and its activity could then be increased about 10-fold upon incubation with ATP-Mg and the catalytic subunit of cyclic-AMP-dependent protein kinase. This activation resulted from a 4.3-fold increase in V and a 2-fold decrease in Km. Both forms of the enzyme were inhibited by sn-glycerol 3-phosphate. From these results it is concluded that the effect of glucose in increasing the concentration of fructose 2,6-bisphosphate in S. cerevisiae is mediated by the successive activation of adenylate cyclase and of cyclic-AMP-dependent protein kinase and by the phosphorylation of 6-phosphofructo-2-kinase by the latter enzyme. In deep contrast with what is known of the liver enzyme, yeast 6-phosphofructo-2-kinase is activated by phosphorylation instead of being inactivated.
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PMID:The mechanism by which glucose increases fructose 2,6-bisphosphate concentration in Saccharomyces cerevisiae. A cyclic-AMP-dependent activation of phosphofructokinase 2. 609 80

Human polymorphonuclear leukocytes were found to respond to the beta-receptor activators, adrenalin and isoproterenol, with a rapid transient increase in cyclic AMP, activation of cyclic AMP-dependent protein kinase, phosphorylase kinase, deactivation of glycogen synthase and glycogen breakdown. This response was unaffected by the presence of 10 mM EGTA. Incubation of leukocytes with phorbol myristate acetate, which stimulates the hexose monophosphate shunt by a Ca2+ mediated mechanism, resulted in activation of phosphorylase without affecting cyclic AMP-dependent protein kinase or phosphorylase kinase activity, thus indicating a Ca2+-mediated activation of phosphorylase. This was, however, unaffected by EGTA. Prolonged incubation with phorbol myristate acetate was found to result in a parallel activation of phosphorylase and glycogen synthase secondary to a pronounced depletion of cellular glycogen. Addition of glucose to polymorphonuclear leukocytes resulted in total conversion of phosphorylase a to the b form and activation of glycogen synthase, however, when EGTA was included, the response to glucose was greatly amplified, thus indicating the synthase conversion is regulated by Ca2+ sensitive mechanisms which do not involve phosphorylase kinase. Addition of adrenalin to cells previously activated by glucose resulted in an increase in the concentration of cyclic AMP and activation of cyclic AMP-dependent protein kinase but deactivation of synthase was not effectuated under these conditions.
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PMID:Effect of glycogenolytic agents on glycogen synthase activity in polymorphonuclear leukocytes. Evidence for a Ca2+-mediated regulation of glycogen synthase activity. 611 51

Recent advances in insulin secretion indicate that pertussis toxin abolishes the inhibition by alpha 2 adrenoceptor activation of insulin release by the pancreas. Pertussis toxin adenosine diphosphate (ADP) ribosylates an inhibitory guanine nucleotide-binding protein (Ni) involved in inhibition of adenylate cyclase. The decrease in cyclic adenosine monophosphate (AMP) by epinephrine may account for its inhibition of insulin release. Insulin interaction with its receptor results in an increase in the tyrosine protein kinase activity of the receptor. Second messengers for insulin are generated, hexose transport is accelerated, and a cyclic AMP-independent protein kinase is activated that phosphorylates at serinethreonine residues. The activity of membrane-bound enzymes such as adenylate cyclase and Ca2+-Mg2+-ATPase is affected. The relative importance of these effects of insulin in its regulation of cellular metabolism remains to be established.
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PMID:Insulin secretion and action. 614 90

Virus induced IFN (IFN alpha or beta) suppresses the antibody response in both mouse and human. The suppression may be related to IFN effect on intermediary metabolism (inhibition of hexose monophosphate shunt) which could result in activation of protein kinase activities. Immune IFN (IFN gamma) also suppresses the antibody response with purified IFN gamma more effective than crude, suggesting that crude IFN gamma preparations contain an antagonist. The cellular interactions that regulate IFN gamma production are similar to those for antibody production with helper and suppressor cell activities. T-cell growth factor or interleukin 2 will mediate helper cell requirements and appears to be an absolute requirement for IFN gamma production.
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PMID:Effect of interferon on antibody formation. 618 7

We have investigated the influence of 2',5' adenosine nucleotides on the replication and transformation of cells by Rous sarcoma virus (RSV). Treatment with the nucleotides ppp2',5'A4 and 2',5'A4 causes a striking reduction (50-fold) in the yield of infectious progeny virus, while ppp2',5A2 and 2',5'A3 had virtually no effect. The reduction in infectivity seen with 2',5'A4 nucleotides is paralleled by a smaller but significant (three- to four-fold) reduction in the amount of particles released as measured by reverse transcriptase activity and levels of viral structural proteins. The reduced infectivity of released particles is not due to viral RNA being missing since the amount of genomic RNA in particles from 2',5'A4-treated cultures was likewise only reduced by a factor of 2-3. Pulse-chase radioactive label experiments showed that processing of both viral group-specific antigens (gag) and viral envelope glycoprotein (env) gene products was completely normal in nucleotide-treated cultures, but that the rate of appearance of viral proteins in mature virus in the culture supernatants was reduced by a factor of about 3-4. Taken together, the data show that assembly of viral structural proteins into virions which can be released into the medium is slowed, and that assembly of virus particles with reduced infectivity follows upon nucleotide treatment. This inhibition of infectious virus production takes place without significant toxic effects on the cell; host protein synthesis is only 20% inhibited. There is also no significant effect on the secretory ability of the cells as measured by total protein release into the medium or release of fibronectin. The transformed cell phenotype was also subtly affected by 2',5'A4, but not by other oligomers. Plasminogen activator protease activity was sharply reduced upon treatment, while other typical features of RSV-transformed cells such as elevated hexose transport, and pp60src-associated protein phosphokinase activity, were little affected.
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PMID:Inhibition of Rous sarcoma virus assembly by treatment with 2',5' adenosine nucleotides. 619 38

The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is an efficient tumour promoter in vivo. In vitro, TPA activates the phospholipid- and Ca2+-dependent protein kinase, kinase C. This activation is believed to reflect the structural similarity between TPA and diacylglycerol, the endogenous protein kinase C activator which is produced in vivo by hydrolysis of phosphatidylinositol (reviewed in ref. 3). Protein kinase C phosphorylates protein substrates at serine and threonine residues in vitro. The effects of TPA on cultured fibroblasts--including enhanced hexose uptake, disruption of actin stress fibres and growth stimulation--are very similar to those induced by certain retrovirus transforming proteins and by peptide growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and multiplication-stimulating activity (MSA). These transforming proteins and mitogenic agents seem to act by inducing tyrosine-specific protein phosphorylation. Such observations suggested that some of the effects of TPA in vivo may be mediated by protein phosphorylation at tyrosine residues. A 42,000-molecular weight (42 K) polypeptide was previously shown to be phosphorylated at tyrosine in cells transformed by avian sarcoma viruses and in cells stimulated by EGF, PDGF or MSA (J. Cooper, personal communication and refs 11 and 12; this polypeptide was originally designated 43 K or spot n in ref. 10). We show here that this polypeptide also becomes phosphorylated at tyrosine in cells treated with TPA. Furthermore, exogenously added diacylglycerol likewise stimulates the phosphorylation of this protein at tyrosine.
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PMID:Phorbol ester and diacylglycerol induce protein phosphorylation at tyrosine. 619 43


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