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)

We found previously that the level of endogenous TRH receptor (TRH-R) mRNA in pituitary (GH3) cells and the level of mouse TRH-R mRNA in GH3 cells stably transfected with mouse pituitary TRH-R cDNA are down-regulated by TRH. This down-regulation is caused by TRH stimulation of TRH-R mRNA degradation via a mechanism that appears to involve protein kinase-C. In this report we study regulation of TRH-R mRNA in monkey kidney (COS-1) cells transiently transfected with mouse pituitary TRH-R cDNA. In transfected COS-1 cells, TRH and phorbol 12-myristate 13-acetate (PMA) caused increases in the level of TRH-R mRNA. In contrast, TRH caused only a small transient increase in the level of the mRNA for the neomycin resistance gene, which was cotransfected with TRH-R, and did not affect the level of the mRNA for glyceraldehyde phosphate dehydrogenase, an endogenous gene. The increases in TRH-R mRNA caused by TRH and PMA were inhibited to similar extents by H-7 (1-[5-isoquinolinesulfonyl]2-methyl piperazine dihydrochloride), an inhibitor of protein kinases. The effect of TRH was observed in cells transfected with expression vectors in which TRH-R cDNA was controlled by cytomegalovirus or Rous sarcoma virus promoters. There was no effect of TRH or PMA on the rate of transcription of the transfected TRH-R cDNA. In contrast, TRH caused the rate of degradation of TRH-R mRNA to decrease from 8.0% to 5.1%/h. Hence, TRH, most likely via a protein kinase-C-mediated mechanism, up-regulates TRH-R mRNA levels in transfected COS-1 cells by decreasing the rate of TRH-R mRNA degradation. Since TRH and PMA down-regulate TRH-R mRNA in GH3 cells, posttranscriptional regulation of TRH-R mRNA is a cell-type specific process.
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PMID:Posttranscriptional up-regulation of thyrotropin-releasing hormone (TRH) receptor messenger ribonucleic acid by TRH in COS-1 cells transfected with mouse pituitary TRH receptor complementary deoxyribonucleic acid. 132 18

Addition of triiodothyronine (T3) to chick-embryo hepatocytes in culture causes increased accumulations of malic enzyme, fatty acid synthase, acetyl-CoA carboxylase and their mRNAs. H-8 and other protein kinase inhibitors inhibited the T3-induced accumulations of these lipogenic enzymes and their mRNAs but had no effect on the activities of 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase, enzymes not induced by T3 in chick-embryo hepatocytes. H-8 also had no effect on the activities of malic enzyme, fatty acid synthase, and acetyl-CoA carboxylase in hepatocytes not treated with T3. Synthesis of soluble protein, levels of mRNAs for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, and induction of metallothionein mRNA by Zn2+ were unaffected by H-8 at concentrations that inhibited the T3-induced accumulation of lipogenic enzymes and their mRNAs. H-8 inhibited T3-induced transcription of the genes for both malic enzyme and fatty acid synthase but had little effect on transcription of the beta-actin or glyceraldehyde-3-phosphate dehydrogenase genes or on total RNA synthesis in isolated nuclei. H-8 also had no effect on binding of T3 to its nuclear receptor. In isolated nuclei, H-8 inhibited phosphorylation of total protein by 15-20%. Phosphorylation of only one major protein was consistently and substantially inhibited, indicating that the effect of H-8 was selective. These results suggest that on-going protein phosphorylation is required specifically for stimulation of transcription of the lipogenic genes by T3.
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PMID:Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl-coenzyme A carboxylase, and their mRNAs are blocked by protein kinase inhibitors. Transcription is the affected step. 168 Jan 29

FSH is the primary hormonal inducer of ovarian follicle maturation and a critically important regulator of steroidogenesis in granulosa cells. We examined possible molecular mechanisms subserving FSH action by assessing concentrations of cytochrome P450 cholesterol side-chain cleavage (P450scc) mRNA in porcine granulosa cells maintained in serum-free culture. Cellular concentrations of specific P450scc mRNA were measured by Northern blot hybridization using a 32P-labeled 1-kilobase porcine cDNA clone. Specificity was tested by estimating the granulosa cell mRNA content of the constitutively expressed enzyme, glyceraldehyde-3-phosphate dehydrogenase. Steroidogenesis was evaluated by measuring concomitant progesterone accumulation in the culture medium. Treatment with ovine FSH (100 ng/ml) increased P450scc mRNA concentrations in a time-dependent fashion, with significant effects on both P450scc mRNA concentrations and progesterone accumulation by 4 h and a maximal increase (8- to 10-fold) at 48 h. FSH dose-response studies at 48 h revealed a significant stimulatory effect of 30 ng/ml FSH on P450scc mRNA accumulation and progesterone production, with a maximal effect at 100 ng/ml FSH. To examine the role of cAMP in mediating granulosa cell P450scc mRNA accumulation, granulosa cells were treated with forskolin, cholera toxin, 8-bromo-cAMP, 8-bromo-cGMP, 5'AMP, or cAMP analogs that differentially stimulate the two isoenzymes of protein kinase-A. Increased specific P450scc mRNA accumulation and progesterone production occurred in response to each agent except 5'AMP and 8-bromo-cGMP. No effects of these agents were observed on glyceraldehyde-3-phosphate dehydrogenase mRNA. To assess possible feedback effects of steroid or sterol on FSH-stimulated P450scc mRNA concentrations, granulosa cells were treated with aminoglutethimide to block or with low density lipoprotein to stimulate steroid production. Inhibition of sterol utilization by the cholesterol side-chain cleavage enzyme had no effect on basal or FSH-stimulated concentrations of P450scc mRNA, but markedly suppressed progesterone production. Low density lipoprotein, which increases intracellular sterol, also did not alter basal or FSH-stimulated P450scc mRNA accumulation, suggesting that neither the utilization nor the availability of sterol regulates specific P450scc mRNA levels. Estradiol alone did not increase P450scc mRNA accumulation, but did augment progesterone production. Treatment of granulosa cells with estradiol and FSH produced a synergistic increase in progesterone concentrations, but did not affect FSH-stimulated P450scc mRNA accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Follicle-stimulating hormone increases concentrations of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage enzyme in primary cultures of porcine granulosa cells. 184 8

An improved method for purifying erythrocyte band 4.1, the protein which mediates the interaction between spectrin and actin, has been developed. The new procedure, using adsorption chromatography on hydroxylapatite crystals immobilized within a crosslinked agarose gel (HA-Ultrogel), is simple and reproducibly provides a high yield of band 4.1 which is essentially free of protein kinase. Other components eluted from the hydroxylapatite matrix include band 4.9, ankyrin, and a 35,000-Da polypeptide that appears to be glyceraldehyde-3-phosphate dehydrogenase that remains bound to the erythrocyte membrane in 150 mM NaCl.
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PMID:Purification of erythrocyte band 4.1 and other cytoskeletal components using hydroxyapatite-Ultrogel. 294 Sep 39

A protein kinase activity responsible for the in vitro phosphorylation of at least six endogenous polypeptides including the large subunit of the ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) is present in the stroma (3000 X g supernatant, S30) of spinach chloroplasts. The phosphorylation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit is strongly enhanced when sodium fluorure is used as a protein phosphatase inhibitor. Phosphorylation occurs on threonine and serine residues. The protein kinase involved is not Ca2+-dependent. There is also evidence for a protein phosphatase activity which suggests a coupled regulation by a phosphorylation-dephosphorylation process. The phosphorylating activity is drastically reduced when S30 is prepared from leaves harvested after a dark period. Phosphorylation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit is not related to its own synthesis. The in vitro phosphorylation of the glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.13) is also demonstrated.
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PMID:Phosphorylation in vitro of the large subunit of the ribulose-1,5-bisphosphate carboxylase and of the glyceraldehyde-3-phosphate dehydrogenase. 303 22

The effect of 2,3-diphosphoglycerate (2,3-P2-glycerate) on the phosphorylation of spectrin in solution by purified membrane cyclic AMP-independent protein kinase and in membrane preparations by the endogenous kinase was investigated. 2,3-P2-Glycerate inhibited spectrin phosphorylation both in solution and in the intact membrane. Kinetic analyses showed that 2,3-P2-glycerate had no effect on the Km for ATP but appeared to lower the Vmax of the reaction. When the effect of 2,3-P2-glycerate was examined in the presence of varying concentrations of spectrin, competitive inhibition kinetics were obtained. Interestingly, low concentrations of 2,3-P2-glycerate were found to effect the release of the membrane kinase from erythrocyte membranes. This release reaction may be related to the ability of 2,3-P2-glycerate to interfere with the interaction between the kinase and spectrin. The data suggest the possibility that the kinase may be bound to spectrin in the erythrocyte membrane. 2,3-P2-glycerate also caused the solubilization of 3-phosphoglyceraldehyde dehydrogenase, but not of cyclic AMP-dependent protein kinase. Taken together, our data indicate that 2,3-P2-glycerate may have a regulatory role in membrane protein phosphorylation and also may regulate the extent of association of the kinase with the membrane.
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PMID:Effects of 2,3-diphosphoglyceric acid on the human erythrocyte membrane phosphorylation system. 627 66

Colchicine, nocodazol, and vinblastine, three microtubule-disrupting drugs, were shown to increase the levels of both nerve growth factor (NGF) mRNA and cell-secreted NGF protein in L929 cells, with levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or amyloid precursor protein (APP) mRNAs remaining unaffected. Northern blot analysis demonstrated that colchicine also increased NGF mRNA levels in rat primary astrocytes and mouse skin fibroblasts. The specificity of the effects observed was assessed by the fact that the microtubule-stabilizing agent Taxotere, a semisynthetic compound structurally related to taxol, suppressed the effects of colchicine, whereas lumicolchicine, a colchicine derivative that has no action on the microtubule network, had no influence on NGF expression. Likewise, the disruption of the microfilament network by cytochalasin B did not increase NGF mRNA levels in L929 cells. Furthermore, the increase in NGF gene expression observed following microtubule disruption depended on a cascade of events involving at least one protein kinase, which is not down-regulated by phorbol ester, and on a pertussis toxin sensitive step. These results support the concept that tubulin and/or the microtubule cytoskeleton play an active role in the regulation of the NGF gene.
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PMID:Expression of the nerve growth factor gene is controlled by the microtubule network. 747 77

Cyclic AMP affinity chromatography applied to various mammalian tissue extracts yielded two proteins in addition to the regulatory subunits of protein kinase. This paper characterizes these proteins and provides a simple procedure for their preparation. The polypeptides (36 kDa and a 19 kDa/21 kDa doublet) were isolated from the cAMP matrix by sequential elution with cAMP solutions of increasing concentrations. Microsequencing was accomplished following chemical or enzymic degradation of isolated polypeptides. Partial amino acid sequences of the 36 kDa protein and analyses of its enzymic activity indicated identity with glyceraldehyde-3-phosphate dehydrogenase whilst the lower MW protein proved to be identical with mammalian nucleoside diphosphate kinase subunits. In both cases, binding to cAMP appeared to occur at the nucleotide (NAD and ATP, respectively) sites. In conclusion, we present a one step-procedure, applicable to tissue and cell extracts, which allows the simultaneous isolation of both glyceraldehyde-3-phosphate dehydrogenase and nucleoside diphosphate kinase. This procedure may help to elucidate the multiple functions of these two important enzymes.
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PMID:Isolation of the myc transcription factor nucleoside diphosphate kinase and the multifunctional enzyme glyceraldehyde-3-phosphate dehydrogenase by cAMP affinity chromatography. 776 89

We analyzed the expression of the dsRNA-dependent protein kinase (PKR) during the activation of murine macrophages to the tumoricidal state by LPS and/or IFNs. LPS induced PKR expression in a dose-dependent manner at levels that were comparable with those observed in response to IFNs. By using the PKR inhibitor 2-aminopurine (2-AP), we have shown that the pathways of macrophage tumoricidal activation elicited by LPS and IFN-alpha beta, but not by IFN-gamma, included a 2-AP-sensitive step. In fact, LPS- and IFN-alpha beta-induced activation was inhibited by 2-AP, whereas the activation by IFN-gamma was not affected by the presence of the inhibitor. 2-AP did not affect the activation of protein kinase C or protein kinase A in intact cells. In the presence of 2-AP the up-regulation of IFN-beta mRNA by LPS was specifically inhibited, whereas the expression of glyceraldehyde-3-phosphate dehydrogenase mRNA or the induction of PKR remained unchanged, thereby demonstrating that 2-AP inhibited selective macrophage genes. The differential sensitivity to 2-AP suggested that the expression of a functional PKR may be required for the macrophage tumoricidal response triggered by LPS and IFN-alpha beta but not IFN-gamma.
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PMID:Potential requirement of a functional double-stranded RNA-dependent protein kinase (PKR) for the tumoricidal activation of macrophages by lipopolysaccharide or IFN-alpha beta, but not IFN-gamma. 799 54

We tested the hypothesis that low density lipoprotein (LDL) metabolism and cellular concentrations of gene transcripts of cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc mRNA) are sites of significant protein kinase-C (PKC) action in the long term (48-h) inhibitory modulation of steroid hormone biosynthesis in ovarian granulosa cells. To this end, we used 12-O-tetradecanoylphorbol-13-acetate (TPA) as an activator of PKC and a monolayer culture system of immature swine granulosa cells responsive to insulin and lipoprotein under serum-free conditions. Insulin-regulated LDL metabolism was identified as a major site of TPA-mediated inhibition of steroidogenesis in granulosa cells. Treatment with TPA (30 ng/ml), but not inactive phorbol base, effectively decreased insulin-stimulated [125I]iodo-LDL binding by 75%, internalization by 90%, and degradation by 75%, as well as delivery and utilization of the [3H]cholesterol moiety of LDL in progesterone biosynthesis by intact granulosa cells. Cellular concentrations of P450scc mRNA, as measured by Northern blot hybridization with a 32P-labeled 1-kilobase porcine cDNA clone, were significantly increased by insulin. This insulin effect was virtually abolished by cotreatment with TPA (30 ng/ml). In contrast, accumulation of mRNA transcripts of a non-steroidogenic gene, 3-phosphoglyceraldehyde dehydrogenase, but not 18S ribosomal RNA, was enhanced by TPA. In summary, major inhibitory actions of PKC activation on granulosa cell steroidogenesis are expressed at specific loci of LDL metabolism, including LDL receptor number, internalization, and degradation, as well as the delivery and utilization of the [3H]cholesterol moiety of LDL to intact granulosa cells. Moreover, a PKC activator suppresses the intracellular accumulation of insulin-stimulated P450scc mRNA, but not that of phosphoglyceraldehyde dehydrogenase or 18S ribosomal RNA. The results obtained in this in vitro study suggest that the inhibition by TPA at these different sites along the steroidogenic pathway may be similar to that which occurs via hormones that work through the PKC system, such as prostaglandin F2 alpha.
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PMID:Sites of inhibition of steroidogenesis by activation of protein kinase-C in swine ovarian (granulosa) cells. 847 49


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