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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nucleolin is a ubiquitous multifunctional protein involved in preribosome assembly and associated with both nucleolar chromatin in interphase and nucleolar organizer regions on metaphasic chromosomes in mitosis. Extensive nucleolin phosphorylation by a casein kinase (CKII) occurs on serine in growing cells. Here we report that while CKII phosphorylation is achieved in interphase, threonine phosphorylation occurs during mitosis. We provide evidence that this type of in vivo phosphorylation involves a mammalian homolog of the cell cycle control Cdc2 kinase. In vitro M-phase H1 kinase from starfish oocytes phosphorylated threonines in a TPXK motif present nine times in the amino-terminal part of the protein. The same sites which matched the p34cdc2 consensus phosphorylation sequence were used in vivo during mitosis. We propose that successive Cdc2 and CKII phosphorylation could modulate nucleolin function in controlling cell cycle-dependent nucleolar function and organization. Our results, along with previous studies, suggest that while serine phosphorylation is related to nucleolin function in the control of rDNA transcription, threonine phosphorylation is linked to mitotic reorganization of nucleolar chromatin.
Mol Cell Biol 1990 Jul
PMID:Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase. 219 60

Monoclonal antibodies which recognize one or only a few keratin polypeptides have been used to study the distribution of different keratins in benign and malignant breast lesions by immunocytochemical methods. Seven monoclonal antibodies which recognized either different keratin polypeptides by immunoblotting techniques, or identified different epithelial cell types in complex tissues were used. In two mastopathies and three fibroadenomas the antibody lu5 stained luminal cells as well as myoepithelial cells. In contrast the antibodies CK7, Troma 1, CK2 and KA4 labeled only luminal cells, whereas antibody CKB1 decorated only myoepithelial cells. All 15 ductal carcinomas showed a uniform staining of tumor cells with the antibodies Troma 1, CK2, KA4 and lu5. The antibody CK7 also stained all ductal carcinomas, but in two specimens the staining was heterogeneous. The antibody CKB1 decorated only the pre-existing myoepithelial cells in 11 of 12 ductal carcinomas but in the remaining specimen the tumor cells were also strongly positive. Tumor cells in lobular carcinomas were labeled by antibodies CK7, Troma 1, CK2, KA4, bu not by CKB1. The antibody CKS1 showed no staining of any of the benign and malignant breast lesions.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Keratin polypeptide distribution in benign and malignant breast tumors: subdivision of ductal carcinomas using monoclonal antibodies. 287 59

The activity of the catalytic alpha subunits of protein kinase CK2 is modulated by interaction with the regulatory beta subunits. In order to define the domains involved in intersubunit contacts, we have applied the two-hybrid system, which a is yeast-based genetic method for the detection of protein-protein interactions in vivo. The data demonstrate that the alpha and beta subunits interact with each other and that the beta subunits, but not the alpha subunits, are able to self-associate. This suggests that the beta subunits play a bridging role in the architecture of the CK2 holoenzyme by linking two alpha:beta heterodimers into a tetrameric complex. Analysis of truncated alpha and beta subunits was used to delimit the subregions necessary for complex formation. The data reveal that the beta subunit is modular in structure, with the two fully separable domains involved in homomeric beta:beta and heteromeric alpha:beta interactions, respectively. Also, beta subunits lacking the autophosphorylation sites in the N termini are able to associate with both the alpha and beta subunits. Furthermore, we find that the N terminus and the evolutionarily less conserved C terminus of the alpha subunit are dispensable for establishing heterodimeric alpha:beta structures.
J Mol Biol 1995 Nov 10
PMID:Genetic dissection of intersubunit contacts within human protein kinase CK2. 747 45

Phosphorylation of microtubule-associated protein MAP1B and the neuronal-specific beta III-tubulin isoform takes place during neurite growth in neuroblastoma cells. Protein kinase CK2 (formerly referred to as casein kinase 2) is possibly involved in beta III-tubulin phosphorylation. As for MAP1B, there are at least two types of phosphorylation; one catalyzed by proline-directed protein kinases and another catalyzed by CK2. Protein kinase CK2 is primarily localized to the nuclei in proliferating neuroblastoma cells, whereas an increased amount of the enzyme is present in the cytoplasm of postmitotic cells bearing neurites. Treatment of neuroblastoma cells with an antisense oligonucleotide which specifically results in CK2 catalytic subunit depletion inhibits neuritogenesis. CK2 depletion is accompanied by dephosphorylation of MAP1B on the corresponding phosphorylatable sites. This dephosphorylation is paralleled by a release of MAP1B from microtubules. These results suggest that MAP1B phosphorylation by CK2 may be required for the assembly of microtubules within neurites. Other neuronal cytoskeletal proteins including MAP1A and tau are also substrates for CK2, indicating a role for the enzyme in the regulation of cytoskeletal functions also in mature neurons.
Cell Mol Biol Res 1994
PMID:Phosphorylation of microtubule-associated proteins by protein kinase CK2 in neuritogenesis. 753 78

1. The use of antisense oligonucleotides to inhibit expression of the genes coding for the catalytic (alpha/alpha') and regulatory (beta) subunits of protein kinase casein kinase 2 (CK2) has allowed study of the role of this enzyme in mouse neuroblastoma cells. 2. Selective depletion of catalytic (alpha/alpha') subunits results in the blocking of neuritogenesis. The depletion of catalytic subunits also affects the sorting of the regulatory (beta) subunit of CK2, as the absence of catalytic subunits prevents the translocation of the regulatory subunit to the nuclei. These results emphasize the existence of a control mechanism linking the expression and sorting of CK2 catalytic and regulatory subunits. 3. Selective depletion of the regulatory (beta) subunit of protein kinase CK2 by an specific antisense oligonucleotide causes partial inhibition of neurite extension.
Cell Mol Neurobiol 1994 Oct
PMID:Depletion of catalytic and regulatory subunits of protein kinase CK2 by antisense oligonucleotide treatment of neuroblastoma cells. 762 3

The enzyme termed nowadays protein kinase CK2 was first described in liver extracts (as a mixture with protein kinase CK1), using casein as artificial substrate, by Burnett and Kennedy (1954). In 1960 it was shown that such casein/phosvitin phosphorylating activity was ubiquitous and distinct from phosphorylase kinase, i.e., the only other protein kinase known at that time. CK1 and CK2 were distinguished from each other at the end of the sixties, and during the seventies CK2 was purified to homogeneity in several laboratories and thoroughly characterized as far as its subunit structure (alpha 2 beta 2), site specificity, and in vitro responsiveness to various effectors were concerned. The first endogenous substrate for CK2 (eIF-3) was described in 1976, but it was during the eighties that it became clear that CK2 is a pleiotropic protein kinase committed with the phosphorylation of a myriad of cellular targets. More than 100 CK2 substrates are known, sharing typical phosphoacceptor sites specified by multiple acidic residues on the C terminal side of Ser/Thr. The definition of the primary structure of CK2 catalytic subunit, in 1987, definitely included CK2 in the big family of eukariotic protein kinases. The growing interest for CK2 is accounted for by its unusual properties, by the increasing number of its substrates, and by several coincidental arguments suggesting that this pleiotropic protein kinase plays a fundamental role in cellular regulation. A major and intriguing problem concerning CK2 is its apparent lack of regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol Res 1994
PMID:A historical view of protein kinase CK2. 773 12

Protein kinase CK2 subunits alpha and beta were expressed either separately or together in a bacterial expression system (pT7-7/BL21(DE3)) and purified to homogeneity. After mixing the subunits, a CK2 holoenzyme (alpha 2 beta 2) was spontaneously reconstituted, which displays identical features as the native enzyme. The alpha subunit alone, although catalytically active by itself, has different biochemical and biophysical properties than the holoenzyme, e.g., it is extremely salt sensitive, already 50 mM monovalent salt can lead to a 50% inhibition of the catalytic activity. Furthermore, it is readily inactivated through urea, protease, and heat treatment. In contrast, the holoenzyme, either reconstituted or native, is much more stable when similar negative insults prevail. The beta subunit has at least three functions: (a) it is necessary for maximum activity of the enzyme under physiological salt conditions, (b) it protects the alpha subunit against denaturing agents or conditions, and (c) it alters the substrate specificity of the alpha subunit. By site-directed mutagenesis, certain functions of the beta subunit could be assigned to specific amino acids or domains. Twenty one mutants of the beta subunit have been prepared and assayed for their ability to assemble with the catalytic alpha subunit to give a fully competent CK2 holoenzyme. The beta subunit contains an acidic stretch (amino acid 55-64), which is obviously responsible for a negative control of enzyme activity since mutations of certain acidic amino acids within this stretch to alanine lead to a hyperactive CK2 holoenzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol Res 1994
PMID:Protein kinase CK2 structure-function relationship: effects of the beta subunit on reconstitution and activity. 773 13

Unlike most Ser/Thr protein kinases which recognize phosphoacceptor sites specified by basic residues, protein kinase CK2 is extraordinarily acidophilic in nature. By combining the analysis of more than 100 CK2 natural phosphorylation sites with the kinetic behaviour of a large number of model peptide substrates, it can be concluded that although the most crucial specificity determinant is an acidic residue (Glu, Asp, TyrP, or SerP) at position +3, additional acidic residues at positions spanning from -2 to +7 (and probably farther) also act as positive specificity determinants for CK2, whereas basic residues at these positions, prolyl residue at position +1, and a bulky hydrophobic doublet at position +1 and +2, are powerful negative determinants. It also appears that the nature of the acidic determinants may variably influence their effect depending on the position occupied: Thus, multiple aspartic acids are, in general, determinants as good as, or even better, than an equivalent number of glutamic acids; an individual Asp at position +3 flanked by Glu residues is ineffective; and phosphorylated residues appear to be much more effective if adjacent to the target residue (positions -2 to +2). In some instances, the local determinants alone are insufficient to account for the phosphorylation efficiency of the substrate which is greatly improved by the overall protein conformation, as illustrated by the examples of CK2 beta-subunit and protein p53, the latter exhibiting no consensus sequence around its phosphorylation site.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol Res 1994
PMID:Substrate specificity of protein kinase CK2. 773 14

A brief overview is presented of progress in the development of specific inhibitors of protein kinases CKI and CKII. Two promising classes of inhibitors, which have the ability to traverse cell membranes, are now known. One of these is based on halogenated benzimidazoles and 2-aza-benzimidazoles (benzotriazoles) and some of their nucleosides. The second embraces modified isoquinoline sulfonamides, several of which are known as inhibitors of other protein kinases. Both classes include analogs that permit discrimination between CKI and CKII. Ongoing research with halogenated benzotriazoles leads to inhibitors with Ki values below 1 microM. Also considered are nucleoside triphosphate analog inhibitors and their potential properties as donors, with illustrative examples from the field of nucleoside kinases, including the apparent existence of a dual-specific viral protein/nucleoside kinase. The role of cellular CKII and viral-encoded CKII-like activities in viral replication underlines the potential of CKII inhibitors as antiviral agents, exemplified by the case of vesicular stomatitis virus.
Cell Mol Biol Res 1994
PMID:Development of inhibitors of protein kinases CKI and CKII and some related aspects, including donor and acceptor specificities and viral protein kinases. 773 15

cDNA clones coding for the alpha and beta subunits of protein kinase 2 (CK2) in zebrafish (Danio rerio) have been isolated. Sequencing of the cDNA clones has demonstrated that one contains the complete coding sequence for the beta subunit of CK2 while the alpha clone is truncated and lacks 183 nucleotides of the 5' coding region. Comparison of the deduced amino acid sequences shows an extremely high degree of evolutionary sequence conservation of these two proteins. Northern analysis of the mRNAs coding for the alpha subunit indicates that this messenger is present in 1 h embryos as a 3.6 Kb and a 1.9 Kb species, both of which decrease in 24-h embryos. In the case of beta, the major mRNA species of approximately 1.7 Kb maintains its level during the period of embryogenesis studied. In situ hybridization of early embryos, using antisense RNAs against alpha and beta mRNAs demonstrates temporal and tissue specific expression patterns. The alpha mRNA decreases after blastula, when it is evenly distributed. The beta mRNA is maintained at high levels between 4 and 24 h of development, showing in 18 h embryos a higher concentration in the developing neural tube and in the embryonic optic and otic vesicles.
Cell Mol Biol Res 1994
PMID:Cloning and expression of genes coding for protein kinase CK2 alpha and beta subunits in zebrafish (Danio rerio). 773 17


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