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)

A protein kinase from wheat germ that phosphorylates the largest subunit of RNA polymerase IIA has been partially purified and characterized. The kinase has a native molecular weight of about 200 kilodaltons. This kinase utilizes Mg2+ and ATP and transfers about 20 phosphates to the heptapeptide repeats Pro-Thr-Ser-Pro-Ser-Tyr-Ser in the carboxyl-terminal domain of the 220-kilodalton subunit of soybean RNA polymerase II. This phosphorylation results in a mobility shift of the 220-kilodalton subunits of a variety of eukaryotic RNA polymerases to polypeptides ranging in size from greater than 220 kilodaltons to 240 kilodaltons on sodium dodecyl sulfate-polyacrylamide gels. The phosphorylation is highly specific to the heptapeptide repeats since a degraded subunit polypeptide of 180 kilodaltons that lacks the heptapeptide repeats is poorly phosphorylated. Synthetic heptapeptide repeat multimers inhibit the phosphorylation of the 220-kilodalton subunit.
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PMID:A protein kinase from wheat germ that phosphorylates the largest subunit of RNA polymerase II. 253 25

Mammalian cells contain two forms of RNA polymerase II, designated IIO and IIA, that differ in the extent of phosphorylation within the C-terminal domain of their largest subunit. Phosphorylation of this domain, which results in the conversion of RNA polymerase IIA to IIO, may play an important role in the transition from the initiation to the elongation phase of transcription. A third form of the enzyme, RNA polymerase IIB, is found in vitro and lacks the repetitive C-terminal domain. Purified calf thymus RNA polymerase IIA was labeled selectively with casein kinase II in the presence of [gamma-32P]ATP and used as substrate for the identification and partial purification of factors that catalyze the conversion of RNA polymerase IIA to IIO. HeLa cell S-100 transcription extracts contain such an activity that cofractionates with factors essential for promoter-dependent transcription through heparin-Sepharose, DEAE-5PW, and DE52 chromatography. The activity is dependent on either ATP, GTP, or dATP, requires a hydrolyzable beta,gamma-phosphoanhydride bond, and cannot utilize pyrimidine nucleoside triphosphates. This observation supports the idea that the conversion activity is a protein kinase. Transcription of the major late promoter of adenovirus-2 was carried out in the presence of a reconstituted transcription extract containing purified RNA polymerases IIO, IIA, or IIB, and the nature of the elongating enzyme was determined by photoaffinity labeling. When the reaction was initiated with RNA polymerase IIO or IIB, nascent transcripts were found cross-linked to subunit IIo or IIb, respectively. However, when the reaction was initiated with RNA polymerase IIA, nascent transcripts were cross-linked to subunit IIo. Consequently, phosphorylation of the C-terminal domain of subunit IIa must have occurred prior to elongation. The copurification of RNA polymerase IIA to IIO conversion activity with factors essential for promoter-dependent transcription and the observation that RNA polymerase II containing an unphosphorylated C-terminal domain is phosphorylated prior to elongation suggest that protein kinases that phosphorylate the C-terminal domain of subunit IIa may play an essential role in transcription.
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PMID:The transition of RNA polymerase II from initiation to elongation is associated with phosphorylation of the carboxyl-terminal domain of subunit IIa. 258 85

Actively transcribing eukaryotic RNA polymerase II is highly phosphorylated on its repetitive carboxyl-terminal domain. We have isolated a protein kinase that phosphorylates serine residues in this repetitive domain. A component of this kinase is cdc2, the product of a cell-cycle control gene previously shown to be a component of M-phase-promoting factor and M-phase-specific histone H1 kinase. This observation suggests a role for the cdc2 protein kinase in transcriptional regulation.
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PMID:Phosphorylation of RNA polymerase by the murine homologue of the cell-cycle control protein cdc2. 266 13

The adenosine analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) is a specific inhibitor for RNA polymerase II transcription in vivo and in vitro [Tamm + Sehgal (1978) Adv. Virus Res. 22, 187-258; Zandomeni & Weinmann (1984) J. Biol. Chem. 259, 14804-14811]. The effect on RNA polymerase II-specific transcription seems to be mediated by its inhibition of nuclear casein kinase II [Zandomeni, Carrera-Zandomeni, Shugar & Weinmann (1986) J. Biol. Chem. 261, 3414-3419]. Inhibition studies indicated that DRB acted as a mixed-type inhibitor with respect to casein and as a competitive inhibitor with respect to the nucleotide phosphate donor substrates. The DRB inhibition constant is 7 microM for the calf thymus casein kinase II, with regard to both ATP and GTP.
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PMID:Kinetics of inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole on calf thymus casein kinase II. 280 63

A protein kinase that phosphorylates Lys(Tyr-Ser-Pro-Thr-Ser-Pro-Ser)4, a synthetic peptide homologous to the evolutionarily-conserved, tandemly-repeated heptapeptide sequence at the C-terminus of the large subunit of eukaryotic RNA polymerase II, has been detected in HeLa cell extracts and chromatographic fractions therefrom. The enzyme, which phosphorylates serine principally, can be distinguished from previously described major protein kinases which phosphorylate the peptide poorly, if at all. It is inhibited by the nucleoside analog, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. Results suggest that human placental RNA polymerase II is phosphorylated at the C-terminus of the large subunit by the partially-purified protein kinase and that the phosphorylation is also sensitive to the nucleoside analog.
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PMID:5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits a HeLa protein kinase that phosphorylates an RNA polymerase II-derived peptide. 293 May 26

We have described a HeLa protein kinase whose activity is inhibited by the nucleotide analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) at concentrations similar to those required to inhibit in vivo and in vitro specific transcription (Zandomeni, R., and Weinmann, R. (1984) J. Biol. Chem. 259, 14804-14822). We have now detected an analogous DRB-sensitive kinase from calf thymus and purified it to homogeneity. Based on the subunit composition of the enzyme and other common biochemical and chromatographic properties, we identified it as casein kinase II. The extent of DRB inhibition of the purified calf thymus enzyme is indistinguishable from that observed for inhibition of in vitro transcription with the HeLa cell extract. The DRB bromo- derivative, 5,6-dibromo-1-beta-D-ribofuranosylbenzimidazole is a more potent inhibitor of in vivo transcription and inhibits purified casein kinase II activity and specific in vitro transcription at 6-10 times lower concentrations than DRB. Moreover, addition of an excess of the purified calf thymus casein kinase II enzyme to a HeLa in vitro transcription reaction inhibited by DRB partially overcomes this inhibition. Thus, we conclude that casein kinase II is involved directly or indirectly in the inhibition by DRB of specific RNA polymerase II-mediated transcription. This demonstrates the participation of a protein kinase in a eukaryotic RNA polymerase II-specific transcription system.
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PMID:Casein kinase type II is involved in the inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole of specific RNA polymerase II transcription. 345 46

We have used a microinjection technique to examine whether injected phosvitin, in its capacity as substrate for casein kinase NII, could compete out the endogenous phosphorylation of some nuclear phosphoproteins with regulatory potential and thereby interfere with the activity of RNA polymerase II. Phosphorylation, which utilizes ATP as phosphate donor, was separated from phosphorylation which uses GTP. Phosvitin introduced into nuclei of salivary gland cells becomes phosphorylated by the endogenous nuclear protein kinase(s) and incorporates phosphates from ATP as well as from GTP. The phosphorylation of nuclear proteins and phosvitin is heparin-sensitive, indicating that they are phosphorylated by casein kinase NII. Microinjected phosvitin does not seem to affect the incorporation of phosphate groups from ATP into nuclear proteins, but protein phosphorylation by GTP is influenced. Apart from a minor overall reduction of 32P-incorporation, the phosphorylation of a 42 kDa nuclear protein, a putative transcription stimulatory factor, and of a 115 kDa nuclear protein was competed out by 70%-80% compared with the control value obtained in the absence of phosvitin. Parallel analyses of DNA transcription in phosvitin-injected nuclei showed that the RNA polymerase II-mediated synthesis of hnRNA and Balbiani ring RNA was diminished by 80% and 90%, respectively. In contrast, the transcription of nucleolar pre-ribosomal 38 S RNA by RNA polymerase I remained unaffected. The inhibitory effect of injected phosvitin could be reversed by in vitro phosphorylation of phosvitin prior to injection, using isolated nuclei as source of protein kinase(s). Taken together, the results suggest a causal relationship between the modification of the GTP-dependent phosphorylation of specific non-histone proteins and the activity of RNA polymerase II.
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PMID:Selective repression of RNA polymerase II by microinjected phosvitin. 347 Jan 71

Purified RNA polymerase II from chicken leukemia cells was found to be an effective substrate for protein kinase C but not cAMP-dependent protein kinase. Protein kinase C catalyzed the incorporation of 1-2 mol of phosphate per mol of polymerase II and the reaction was totally calcium and lipid dependent. Electrophoresis studies revealed a time-dependent increase of phosphate incorporation into RNA polymerase II subunits of 220 KDa, 180 KDa and 150 KDa, with a preferential phosphorylation of the 180 KDa polypeptide. The phosphorylated enzyme has a preference for using single-stranded DNA as the template for transcription, including transcription of the single-stranded myb oncogene sequence. Phosphoamino acid analysis indicated that both serine and threonine residues were phosphorylated at equal amounts. Phosphorylation by protein kinase C increased the affinity of substrate-polymerase binding and the initial rate of RNA synthesis, suggesting a mechanism by which gene expression can be activated by protein kinase C.
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PMID:Protein kinase C phosphorylates leukemia RNA polymerase II. 347 67

RNA polymerase II-specific transcription requires, in addition to auxiliary protein factors, the hydrolysis of the beta-gamma phosphate bond of ATP. The nonhydrolyzable analog of ATP, imidoadenosine triphosphate does not suffice for specific in vitro transcription (Bunick, D., Zandomeni, R., Ackerman, S., and Weinmann, R. (1982) Cell 29, 877-886), although it can be incorporated into RNA. The experiments presented here suggest two energy-dependent steps in RNA polymerase II transcription. One of these steps is required at, or close to, the point of initiation, as determined by 5' end primer extension analysis. In vitro transcription occurs efficiently in vitro when imidoadenosine triphosphate is supplemented with dATP to fulfill the energy requirement. In the presence both of imidoadenosine triphosphate and imidoguanosine triphosphate, the concentration of dATP required for transcription initiation is dramatically increased. This suggests that ATP and GTP are co-substrates in transcription initiation, supporting the role of protein kinase II in this process (Zandomeni, R., Zandomeni, M. C., Shugar, D., and Weinmann, R. (1986) J. Biol. Chem. 261, 3414-3419). The concentration of dATP required for maximal initiation is inadequate for the production of full-length transcripts, suggesting a second energy-dependent step in the RNA elongation process. Since the elongation step is unaffected by the presence of imidoguanosine triphosphate, GTP beta-gamma phosphate bond hydrolysis appears to be required only for initiation.
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PMID:Purine triphosphate beta-gamma bond hydrolysis requirements for RNA polymerase II transcription initiation and elongation. 369 65

During a study on the role of cyclic nucleotides on the RNA polymerase activities of isolated fetal calf liver nuclei, it was observed that cGMP enhanced the RNA polymerase activity in the presence of Mg++ at low ionic strength, conditions which are appropriate for the measurement of the RNA polymerases I and III. However, the cGMP-dependent stimulation was sensitive to low concentrations of alpha-amanitin, indicating an effect on the activity of the RNA polymerase II. For this reason the effect of cGMP was tested again using purified RNA polymerase II preparations from calf thymus devoid of RNA polymerases I and III. cGMP stimulated activity of the purified RNA polymerase II at concentrations of 1 and 10 nM. cGMP also caused a small but significant stimulation of the protein kinase activity associated with the enzyme preparations of the RNA polymerase used.
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PMID:Effect of cGMP on RNA polymerase II activities in fetal calf liver nuclei and in purified enzyme preparations. 609 9


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