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:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to characterize two cis-diamminedichloroplatinum(II) (CDDP) resistant cell lines established from human larynx carcinoma HEp2 cells through repeated treatments with increased CDDP concentrations. CK2 cells obtained by continuous treatments were more resistant to CDDP than CA3 cells obtained by acute treatments. The examination of growth characteristics showed that both CDDP resistant cells had doubling times identical to that of the parental cells, but had lower plating efficiency. The possible involvement of glutathione (GSH), glutathione transferases (GST), metallothioneins, P-glycoprotein and drug accumulation in CDDP resistance was examined. Glutathione contents were elevated in both CDDP resistant lines. However, neither GSH nor GST were involved in CDDP resistance. This was demonstrated by simultaneous incubation of parental and CDDP resistant cells with CDDP and specific inhibitors of GSH and GST alpha and pi (buthionine sulfoximine and ethacrinic acid). Similarly, verapamil, an inhibitor of P-glycoprotein, did not influence the sensitivity of parental and resistant cells to CDDP. As compared to the parental cells, CK2 cells became resistant and CA3 cells became sensitive to cadmium, indicating increased level of metallothioneins in CK2 cells, and reduced level in CA3 cells. Measurements of platinum contents in parental and CDDP resistant cells after 1, 3 and 6 hours exposure to 70 mumol CDDP showed reduction in platinum accumulation after each exposure time in CK2 cells, and after 6 hours exposure in CA3 cells. This study identified decreased platinum accumulation as an important mechanism of CDDP resistance in human larynx carcinoma cells.
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PMID:Human larynx carcinoma cells resistant to cis-diamminedichloroplatinum(II): mechanisms involved in the resistance. 793 85

CK2 (formerly called casein kinase 2) is a ubiquitous messenger-independent serine/threonine protein kinase implicated in cell growth and proliferation. To investigate the regulation and functions of this enzyme, experiments were carried out to search for CK2-interacting proteins. The methods employed included an overlay technique, co-purification, co-immunoprecipitation, and the use of glutathione S-transferase (GST) CK2 fusion proteins. By the CK2 overlay technique, one protein of 110 kDa was found to bind to CK2 with very high affinity. The binding was inhibited by CK2 effectors such as heparin, polyarginine, and histone H1, but was not affected by the CK2 substrate, casein. Protein p110 was also detected by co-immunoprecipitation using anti-CK2 antiserum, suggesting an in vivo association of this protein with CK2. Co-purification of p110 with CK2 from Sf-9 cells that overexpressed CK2 was also observed through sequential chromatographic steps. Using GST fusion proteins of CK2, the CK2-p110 interaction was investigated further and was found to occur primarily through CK2 alpha or alpha' subunits, but not the beta subunit. Protein p110 was purified from 3T3 L1 mouse fibroblast cell lines using a GST-CK2 affinity resin. Amino acid sequence analysis of peptides obtained from the protein indicated that it is the nuclear protein, nucleolin. Furthermore, p110 was recognized by anti-nucleolin antiserum. At present, the physiological significance of the strong interaction between CK2 and nucleolin, an excellent substrate for the enzyme, is not clear. However, this association may be important for regulating rDNA transcription.
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PMID:The physical association of casein kinase 2 with nucleolin. 866 58

BTF3, initially discovered as a factor required for transcription inititation of RNA polymerase II, is expressed in two isoforms, termed a and b. BTF3b, the transcriptionally inactive isoform, was identified as an interaction partner of protein kinase CK2 subunit beta employing the interaction trap system for screening ofa HeLa cDNA fusion library. We report here on the interaction between the other isoform, BTF3a, and protein kinase CK2. The complete cDNA of BTF3a was cloned by RT-PCR and used for analysis in the two-hybrid system with a three-reporter yeast strain. Interaction of BTF3a with CK2 subunits alpha, alpha' or beta was detectable by one of three reporters, whereas the CK2beta - BTF3a interaction was activating two reporters. It was also shown that BTF3a is phosphorylated in vitro by the alpha2beta2 holoenzyme, but not by alpha or alpha' alone, indicating the requirement of beta for substrate recognition. Immunoprecipitations of GST-fused BTF3a carried out in vitro resulted in co-precipitation of beta. Similarly, GST-BTF3a, but not GST alone isolated with glutathione agarose beads from buffer containing recombinant CK2 subunits was found complexed with alpha and beta, likely representing alpha2beta2 holoenzyme. The data show a weak, nevertheless specific interaction of protein kinase CK2 via subunit beta with the putative transcription factor BTF3a in vitro and in vivo, and a role of BTF3a as a potential new substrate for CK2.
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PMID:BTF3 is a potential new substrate of protein kinase CK2. 1009

In order to aid in an understanding of the cellular functions of protein kinase CK2, a search for interacting proteins was carried out using a 32P-labeled CK2 overlay method. Several proteins were found to associate with CK2 by this assay; among them, one protein of 110 kDa appeared to be the most prominent one. The possible association of CK2 with p110 was suggested by experiments involving the co-immunoprecipitation using anti-CK2 antibodies. Further analysis using GST-CK2 fusion proteins demonstrated that the CK2-p110 interaction occurred through the CK2alpha/alpha' subunits. To identify p110, it was purified using a GST-CK2 affinity column, and internal amino acid sequencing was then performed. p110 was found to be nucleolin, a nucleolar protein that may be important for rRNA synthesis; a possible role of CK2 in the control of this process is suggested. Using the same CK2 overlay technique, another interacting protein, insulin receptor substrate 1 (IRS-1), was also identified. By applying a modified overlay method using individual 35S-labeled CK2 subunits, obtained by in vitro translation in rabbit reticulate lysates, it was determined that CK2 associates with IRS-1 through its alpha/alpha' subunits; i.e. in keeping with the fact that IRS-1 is a known substrate for CK2. However, further work is needed to examine the association of CK2 with IRS-1 in vivo in order to fully understand the significance of the interaction.
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PMID:Identification of proteins that associate with protein kinase CK2. 1009 12

By interaction cloning (yeast two-hybrid system) using the catalytic domain of protein kinase Czeta (PKCzeta) as bait, we cloned a human full-length cDNA with 62% nucleotide homology to the A6 protein recently cloned and characterized by Beeler et al. [Beeler, J.F., LaRochelle, W.J., Chedid, M., Tronick, S.R. & Aaronson, S. A. (1994) Mol. Cell. Biol. 14, 982-988]. The deduced amino acid sequence (349 amino acids) of the A6-related protein (A6rp) contained potential actin-binding sites and ATP-binding sites. We also cloned the murine homolog of A6rp. Human A6rp was expressed in an in-vitro transcriptional/translational system with an apparent molecular mass of 40 kDa and as a glutathione S-transferase (GST) fusion protein in bacteria. A polyclonal anti-(A6rp) was raised in rabbits and used for the identification of A6rp by immunoblotting. A6rp was found to be expressed at the mRNA and the protein levels in all cells and tissues investigated. GST-A6rp was phosphorylated by PKCzeta but not significantly by other PKC isoenzymes. Moreover, it was phosphorylated by casein kinase 2 and most effectively by the tyrosine kinase Src. In contrast to GST-A6rp, GST-A6 was also phosphorylated by PKC isoforms other than PKCzeta and strongly by CK2, but just weakly by Src. In contrast to the results of Beeler et al. on beta-galactosidase-A6, we were unable to demonstrate autokinase activity or tyrosine phosphorylation of either GST-A6 or GST-A6rp. In accordance with the potential ATP-binding sites, both proteins were able to bind ATP.
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PMID:Cloning, expression and characterization of an A6-related protein. 1040 62

Using GST-EF-1 delta as an exogenous substrate, and EF-1 delta kinase activity was shown to increase transiently during early development of sea urchin embryos. The basal activity of EF-1 delta kinase in unfertilized eggs was 150 fmoles/min/mg protein. The activity began to increase 10 h after fertilization and reached its maximum level (8.4 x basal) at 24 h. The activity then declined to twice the basal value at 72 h post-fertilization. The EF-1 delta kinase activity was identified to a CK2-type enzyme on the basis of its substrate specificity for EF-1 delta, crude casein and beta casein, its inhibition by heparin, DRB, 2,3-bisphosphoglycerate, and its stimulation by spermine, spermidine, and polylysin. Furthermore, the activity was inhibited by the synthetic peptide RRREEETEEE specific for CK2. DRB (200 microM) and 2,3-bisphosphoglycerate (2.5 mM) blocked or delayed the transition from blastula to gastrula of the embryos, suggesting a role for the kinase in early development.
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PMID:Transient increase of a protein kinase activity identified to CK2 during sea urchin development. 1060 May 19

Salicylic acid (SA) activates immediate early transcription of genes controlled by a family of DNA promoter elements named as-1-like elements. These elements are functional in the promoter of glutathione S-transferase genes. We have previously shown that SA increases the binding of tobacco (Nicotiana tabacum cv Xanthi nc) nuclear factors to the as-1 sequence in a process mediated by protein phosphorylation. In this study we give evidence for the participation of a nuclear protein kinase CK2 (casein kinase 2) in the pathway activated by SA in tobacco. The first line of evidence comes from the evaluation of the CK2 activity in nuclear extracts prepared from tobacco plants treated with SA or water as a control. Results from these experiments indicate that SA increases the nuclear CK2 activity. The second line of evidence derives from the evaluation of the in vivo effect of 5,6-dichloro-1-(beta-D-ribofuranosyl) benzimidazole (DRB), a cell-permeable CK2 inhibitor, on the responsiveness of the as-1 sequence to SA. Results from these experiments indicate that DRB impairs the activating effect of SA on the transcription of both, the GUS reporter gene controlled by a tetramer of the as-1 element, and the endogenous gnt35 gene encoding a glutathione S-transferase, in transgenic tobacco plants. DRB also impaired the increasing effect of SA on the binding of nuclear factors to the as-1 element. Furthermore, transcription of the as-1/GUS reporter gene activated by the synthetic auxin 2,4-dichlorophenoxyacetic acid and by methyl jasmonate was also inhibited by DRB. To our knowledge, this is the first report in which activation of a CK2 enzyme by a plant hormone is reported.
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PMID:A nuclear casein kinase 2 activity is involved in early events of transcriptional activation induced by salicylic acid in tobacco. 1115 47

Protein kinase CK2 is a ubiquitous protein that phosphorylates multiple substrates and is composed of catalytic (alpha, alpha') and regulatory (beta) subunits. Abundant evidence relates CK2 to the regulation of cell division. p21(WAF1/CIP1) is a potent inhibitor of cyclin-dependent kinases and of DNA replication and acts as a key inhibitor of cell cycle progression. In this work we examine the relation between these two important proteins. The interaction between the CK2 beta regulatory subunit of CK2 and p21(WAF1/CIP1) has been confirmed. Using a pull-down assay and fusion constructs of glutathione transferase with fragments of CK2 beta and other mutants, it was possible to define that the N-terminal (1-44) portion of CK2 beta contains a p21(WAF1/CIP1) binding site. CK2 reconstituted from recombinant alpha and beta subunits can phosphorylate p21(WAF1/CIP1) in vitro. This phosphorylation is greatly enhanced by histone H1. p21(WAF1/CIP1) can inhibit the phosphorylation of substrate casein by CK2. This inhibition, however, seems to be due to competition by p21(WAF1/CIP1) as an alternate substrate since in order to observe inhibition it is necessary that the concentration of p21 be of the same order of magnitude as the casein substrate concentration. This competition is not related to the binding of p21(WAF1/CIP1) to CK2 beta because it can also be observed when, in the absence of CK beta, CK alpha is used to phosphorylate casein in the presence of the p21.
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PMID:Protein p21(WAF1/CIP1) is phosphorylated by protein kinase CK2 in vitro and interacts with the amino terminal end of the CK2 beta subunit. 1125 27

Protein kinase CKII is a Ser/Thr kinase which is involved in many proliferation-related processes in the cell. p47(phox) is a component of the leukocyte NADPH oxidase, which is an important element of host defense against microbial infection. In this study, we demonstrate that a truncated form of the p47(phox) lacking its N-terminal region (p47(phox)/SH3-C), but not a truncated form of the p47(phox) lacking its C-terminal region (p47(phox)/N-SH3), undergoes better phosphorylation by CKII in the presence of arachidonic acid. The yeast two-hybrid test and the glutathione S-transferase (GST) pull-down assay showed that p47(phox) interacts specifically with the regulatory beta subunit (CKIIbeta), but not with the catalytic alpha subunit (CKIIalpha) of the tetrameric CKII holoenzyme. The binding of p47(phox) to CKIIbeta requires the C-terminal region of p47(phox) and is completely abolished by addition of spermine, indicating that a highly basic region in the C-terminal region of p47(phox) contributes to binding to CKIIbeta. In addition, p47(phox) stimulates the catalytic activity of CKII holoenzyme; this stimulation also requires the C-terminal region of p47(phox). Coimmunoprecipitation experiments showed that CKII holoenzyme interacts with p47(phox) in human neutrophils. Taken together, the present data indicate that the C-terminal region of p47(phox) plays a significant role in the arachidonic acid-dependent phosphorylation of p47(phox) by CKII and that the same region of p47(phox) associates directly with CKIIbeta and can modulate the catalytic activity of CKII holoenzyme.
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PMID:Regulation of protein kinase CKII by direct interaction with the C-terminal region of p47(phox). 1148 12

Protein kinase CK2 is a tetrameric enzyme comprised of two regulatory subunits (CK2beta) and two catalytic subunits (CK2alpha and/or CK2alpha'). The crystal structure of dimeric CK2beta demonstrated that a zinc finger mediates CK2beta dimerization, therefore we constructed a mutant in which cysteine residues 109 and 114 were mutated to serine. Our objectives were to examine the effects of disrupting the zinc finger of the regulatory CK2beta subunit on CK2 tetramer assembly. Examination of this zinc-finger-deficient mutant of CK2beta using a yeast two-hybrid assay demonstrates that the mutant fails to form CK2beta homodimers. In order to extend these studies, we co-transfected COS-7 cells with epitope-tagged constructs and performed co-immunoprecipitation assays. The results from these studies demonstrate that the mutant fails to form CK2beta homodimers and fails to interact with catalytic CK2 subunits. Furthermore, we demonstrate that the mutant CK2beta is not appreciably phosphorylated in cells. Using in vitro binding assays, we demonstrated that the mutant CK2beta protein fails to interact with glutathione S-transferase-CK2alpha'. Finally, we demonstrate that the mutant is translated at an equivalent rate to wild-type CK2beta, but is degraded much more rapidly. Overall, our results are consistent with the model that beta-beta dimerization precedes incorporation of catalytic subunits into tetrameric CK2 complexes, and that beta-beta dimerization is a prerequisite for the stable incorporation of catalytic subunits into CK2 complexes.
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PMID:Assembly of protein kinase CK2: investigation of complex formation between catalytic and regulatory subunits using a zinc-finger-deficient mutant of CK2beta. 1148 55


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