Isolation and characterization of human cDNA clones encoding the .alpha. and the .alpha.' subunits of casein kinase II

Lozeman, Fred J.; Litchfield, David W.; Piening, C.; Takio, Koji; Walsh, Kenneth A.; Krebs, Edwin G.

doi:10.1021/bi00488a034

Cited by 156 publications

(116 citation statements)

References 84 publications

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“…One question that could be raised is whether ␣ and ␣Ј subunits exhibit redundancy in vertebrates as they do in yeast (5). It is known that CK2␣ and CK2␣Ј are encoded by different genes (22) and that they are structurally very homologous (85% homology) with major differences only in the COOH terminus (4). It has been shown that the ␣ subunit can act as a transcription factor to control ␤ gene expression, whereas ␣Ј cannot (37).…”

Section: Discussionmentioning

confidence: 99%

“…The cDNA for each deletion mutant was obtained by polymerase chain reaction amplification of human CK2␤ in Bluescript KS plasmid (22). For NH 2 -terminal deletion mutations, the sense polymerase chain reaction primers were: 5Ј-GC-GGATCCTTCTTCTGTGAAGTGGATG-3Ј (GST-␤ ); 5Ј-GCGGATC-CGAGCAGGTCCCTCACTATC-3Ј (GST-␤ 41-215 ); 5Ј-GCGGATCCGGA-TTGATCCACGCCCGCT-3Ј (GST-␤ 81-215 ); 5Ј-GCGGATCCCCCATTGG-CCTTTCAGACA-3Ј (GST-␤ 121-215 ); and 5Ј-GCGGATCCGATGTGTAC-ACACCCAAGT-3Ј (GST-␤ 142-215 ).…”

Section: Methodsmentioning

confidence: 99%

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Specific Interaction between Casein Kinase 2 and the Nucleolar Protein Nopp140

Meier

Dobrowolska

et al. 1997

Journal of Biological Chemistry

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105

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Casein kinase 2 (CK2) is a multifunctional second messenger-independent protein serine/threonine kinase that phosphorylates many different proteins. To understand the function and regulation of this enzyme, biochemical methods were used to search for CK2-interacting proteins. Using immobilized glutathione S-transferase fusion proteins of CK2, the nucleolar protein Nopp140 was identified as a CK2-associated protein. It was found that Nopp140 binds primarily to the CK2 regulatory subunit, ␤. The possible in vivo association of Nopp140 with CK2 was also suggested from a coimmunoprecipitation experiment in which Nopp140 was detected in immunoprecipitates of CK2 prepared from cell extracts. Further studies using an overlay technique with radiolabeled CK2 as a probe revealed a direct CK2-Nopp140 interaction. Using deletion mutants of CK2␤ subunits, the binding region of the CK2␤ subunit to Nopp140 has been mapped. It was found that the NH 2 -terminal 20 amino acids of CK2␤ are involved. Since Nopp140 has been identified as a nuclear localization sequence-binding protein and has been shown to shuttle between the cytoplasm and the nucleus, the finding of a CK2-Nopp140 interaction could shed light on our understanding of the function and regulation of CK2 and Nopp140.Protein phosphorylation is known to be a very important means of cellular regulation, and in recent years much information about protein kinases and phosphatases, especially those involved in the mitogen-activated protein kinase pathway, has been obtained (for review, see Refs. 1-3). Little is known, however, about the function and regulation of one particular protein kinase, casein kinase 2 (CK2), 1 although increasing data suggest that it may be an important mediator in mitogenic signal transduction (for review, see Ref. 4).CK2 is a multifunctional, second messenger-independent eukaryotic protein serine/threonine kinase present in the nucleus and cytoplasm of all eukaryotic cells. The holoenzyme form is generally composed of catalytic subunits ␣, ␣Ј, and a regulatory subunit ␤ combined so as to form ␣ 2 ␤ 2 , ␣␣Ј␤ 2 , or ␣Ј 2 ␤ 2 heterotetramers. The ␣ and ␣Ј subunits are catalytically active, whereas the ␤ subunit is inactive but can stimulate the catalytic activity of ␣ and ␣Ј under certain circumstances. Furthermore, the ␤ subunit stabilizes the ␣ and ␣Ј subunits and can facilitate substrate recognition (4). CK2 is widely expressed, and its sequence is highly conserved throughout evolution, indicating that the enzyme may have a critical role in cell function. In fact, it has been shown in Saccharomyces cerevisiae that the simultaneous disruption of genes encoding CK2 ␣ and ␣Ј subunits is lethal (5). CK2 phosphorylates a large number of proteins including enzymes involved in nucleic acid synthesis, transcription and protein synthesis factors, structural proteins, and signal transduction proteins, suggesting a global role in the regulation of cellular processes (6). Several recent studies demonstrate that CK2 is important for cell growth and division. Fir...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Specific Interaction between Casein Kinase 2 and the Nucleolar Protein Nopp140

Meier

Dobrowolska

et al. 1997

Journal of Biological Chemistry

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105

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“…The a catalytic subunit is stimulated by the b regulatory subunit, which undergoes autophosphorylation. 24 This kinase is present in both the cytoplasmic and nuclear compartments. CK2 is known to phosphorylate a variety of transcription factors in vivo and in vitro so that their activities are either positively or negatively modulated.…”

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confidence: 99%

Role for casein kinase 2 in the regulation of HIF‐1 activity

Mottet

Ruys

Demazy

et al. 2005

Intl Journal of Cancer

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Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that plays a major role in cellular adaptation to hypoxia. The mechanisms regulating HIF-1 activity occurs at multiple levels in vivo. The HIF-1a subunit is highly sensible to oxygen and is rapidly degraded by the proteasome 26S in normoxia. Activation in hypoxia occurs through a multistep process including inhibition of HIF-1a degradation, but also increase in the transactivation activity of HIF-1. Several data indicate that phosphorylation could play a role in this regulation. In this report, we investigated the role of casein kinase 2 (CK2), an ubiquitous serine/ threonine kinase, in the regulation of HIF-1 activity. Hypoxia was capable of increasing the expression of the b subunit of CK2, of inducing a relocalization of this subunit at the plasma membrane, of inducing nuclear translocation of the a subunit and of increasing CK2 activity. Three inhibitors of this kinase, DRB (5,6-dichloro-1-b-D-ribofuranosyl-benzimidazole), TBB (4,5,6,7-tetrabromotriazole) and apigenin, as well as overexpression of a partial dominant negative mutant of CK2a, were shown to inhibit HIF-1 activity as measured by a reporter assay and through hypoxiainduced VEGF and aldolase expression. This does not occur at the stabilization process since they did not affect HIF-1a protein level. DNA-binding activity was also not inhibited. We conclude that CK2 is an important regulator of HIF-1 transcriptional activity but the mechanism of this regulation remains to be determined. Since HIF-1 plays a major role in tumor angiogenesis and since CK2 has been described to be overexpressed in tumor cells, this new pathway of regulation can be one more way for tumor cells to survive. ' 2005 Wiley-Liss, Inc.Key words: casein kinase 2; HIF-1; neoangiogenesis HIF-1 (hypoxia-inducible factor-1) is a key regulator of cell response to reduced oxygen level. In response to hypoxic conditions, HIF-1 increases the expression of downstream target genes such as erythropoietin (EPO), vascular endothelial growth factor (VEGF) and glycolytic enzymes (aldolase A, enolase-a) and mediates adaptation of cells to decreased oxygen level. 1 The role of HIF-1 in the regulation of tumor growth by hypoxia via the initiation of angiogenesis is certainly the best example of such an adaptive response. 2 Oncogene activation and tumor-suppressor inactivation result in deregulated cellular proliferation. However, most tumors grown larger than 1 mm 3 contain regions of low oxygen tension (hypoxia) due to an imbalance between oxygen supply and consumption. Formation of new blood vessels or ''neoangiogenesis'' is thus essential for further tumor growth. It is also important to allow tumor cell dissemination at distant sites, i.e., metastasis.Several studies using HIF-1 mutant cells have shown that HIF-1 has a profound effect on tumor biology. For example, tumors grown from HIF-1a-defective embryonic stem cells display abnormal vascularity and reduced growth rate. 3 Moreover, HIF-1 is upregulated in a broad r...

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“…Our results indicate that the CKII a and ß subunits are localized in the cytoplasm C ASEIN kinase II (CKII)' is a ubiquitous protein serlne/threonine kinase found in eukaryotic cells (Edelman et al . 1987 and highly conserved among eukaryotic organisms, including Drosophila, yeast, C. elegans, bovine, and human (Saxena et al ., 1987;Chen-Wu et al ., 1988;Hu and Rubin, 1990a ;Lozeman, 1990). Casein kinase II from several species share a common polypeptide subunit structure, a2ß2, with a of M 37,000-44,000 and ß of M 24,000-28,000 by electrophoresis (Edelman et al ., 1987) .…”

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confidence: 99%

“…The structures of cDNA clones for human CKII a and a' have been determined, and the molecular weights of the a and a' predicted from the human cDNAs were 45,160 and 41,450, respectively (Lozeman et al, 1990) . The amino acid sequence of the ß subunit was initially derived by sequencing the isolated subunit from bovine lung (Takio et al ., 1987), and the human CKII ß cDNA has been isolated as well, giving the predicted molecular weight of 24,925 (Jakobi et al, 1989) .…”

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confidence: 99%

Immunocytochemical localization of casein kinase II during interphase and mitosis.

Spector

Bae

et al. 1991

The Journal of Cell Biology

119

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Abstract. We have developed specific antibodies to synthetic peptide antigens that react with the individual subunits of casein kinase 11 (CKII) . Using these antibodies, we studied the localization of CKII in asynchronous HeLa cells by immunofluorescence and immunoelectron microscopy. Further studies were done on HeLa cells arrested at the Gl/S transition by hydroxyurea treatment . Our results indicate that the CKII a and ß subunits are localized in the cytoplasm C ASEIN kinase II (CKII)' is a ubiquitous protein serlne/threonine kinase found in eukaryotic cells (Edelman et al . 1987 and highly conserved among eukaryotic organisms, including Drosophila, yeast, C. elegans, bovine, and human (Saxena et al ., 1987;Chen-Wu et al ., 1988;Hu and Rubin, 1990a ;Lozeman, 1990). Casein kinase II from several species share a common polypeptide subunit structure, a2ß2, with a of M 37,000-44,000 and ß of M 24,000-28,000 by electrophoresis (Edelman et al ., 1987) . Two forms of a are known designated a (M 41,000-44,000) and a' (M, 37,000-42,000) . The a and a' subunits are thought to be the catalytic subunits based on their kinase activity in the absence of the ß subunit and sequences common to other protein kinases (Hathaway et al ., 1981; Cochet and Chambaz, 1983 ;Chen-wu et al ., 1988 ;Meisner et al., 1989;. The function of the ß subunit is unknown, and it shares no extensive homology to other known protein sequences (Jakobi et al ., 1989) . The ß subunit has a high degree of polarity with clusters ofnegative charges in the amino-terminal region and positive charge clusters in the carboxy-terminal region (Takio et al., 1987) . The basic compounds, spermine, spermidine, and polylysine, stimulate activity by interacting at least in part with the ß subunit (Traugh et al ., 1990) . This subunit may have a regulatory role in the holoenzyme (Takio et al., 1987), and evidence supporting this has been found in A-431 cells (Ackerman et al ., 1990). The comparative studies using the native CKII holoenzyme and the bacterially expressed a subunit show that the expressed a is inhibited by heparin, but it is not stimulated by polyamines and has 9% of K t of the holoenzyme (Hu and Rubin, 1990b during interphase and are distributed throughout the cell during mitosis . Further electron microscopic investigation revealed that CKII a subunit is associated with spindle fibers during metaphase and anaphase. In contrast, the CKII a' subunit is localized in the nucleus during GI and in the cytoplasm during S. Taken together, our results suggest that CKII may play significant roles in cell division control by shifting its localization between the cytoplasm and nucleus .further suggests that CKII holoenzyme is stabilized by interaction with the ß subunit .

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Isolation and characterization of human cDNA clones encoding the .alpha. and the .alpha.' subunits of casein kinase II

Cited by 156 publications

References 84 publications

Specific Interaction between Casein Kinase 2 and the Nucleolar Protein Nopp140

Specific Interaction between Casein Kinase 2 and the Nucleolar Protein Nopp140

Role for casein kinase 2 in the regulation of HIF‐1 activity

Immunocytochemical localization of casein kinase II during interphase and mitosis.

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