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PubMed2006

Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction.

The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic specializations. We observed CK2-mediated phosphorylation of serine residues within the kinase insert (KI) of MuSK. Inhibition or knockdown of CK2, or exchange of phosphorylatable serines by alanines within the KI of MuSK, impaired acetylcholine receptor (AChR) clustering, whereas their substitution by residues that imitate constitutive phosphorylation led to aggregation of AChRs even in the presence of CK2 inhibitors. Impairment of AChR cluster formation after replacement of MuSK KI with KIs of other receptor tyrosine kinases correlates with potential CK2-dependent serine phosphorylation within KIs. MuSK activity was unchanged but AChR stability decreased in the presence of CK2 inhibitors. Muscle-specific CK2beta knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function. This is the first description of a regulatory cross-talk between MuSK and CK2 and of a role for the KI of the receptor tyrosine kinase MuSK for the development of subsynaptic specializations.

Amino Acid Sequence↗
PubMed2003

Cilostazol enhances casein kinase 2 phosphorylation and suppresses tumor necrosis factor-alpha-induced increased phosphatase and tensin homolog deleted from chromosome 10 phosphorylation and apoptotic cell death in SK-N-SH cells.

This study shows the signaling pathway by which cilostazol suppresses tumor necrosis factor-alpha (TNF-alpha)-induced the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) phosphorylation and apoptosis via casein kinase 2 (CK2) phosphorylation in the SK-N-SH cells (neuroblastoma cells). Cilostazol (10 microM) fully restored cell proliferation with suppression of DNA fragmentation induced by TNF-alpha and emodin, a CK2 inhibitor, which were antagonized by iberiotoxin, a maxi-K channel blocker. Under application of TNF-alpha or emodin, increased PTEN phosphorylation and decreased phosphorylation of CK2/Akt/cyclic AMP response element-binding protein (CREB), and CK2 activity were significantly reversed by cilostazol (approximately 1-100 microM), all of which were antagonized by iberiotoxin. 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS-1619) and (3S)-(+)-(5-chloro-2-methoxyphenyl-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one (BMS 204352) maxi-K channel openers significantly elevated CK2 activities that were reversible by iberiotoxin. SK-N-SH cells treated with antisense CK2 oligodeoxynucleotide showed a prominent DNA fragmentation with little responsiveness to TNF-alpha in the phosphorylation of PTEN, indicative of the essential role of p-CK2/CK2 in cell proliferation, and the decreased cell viability of these cells was not restored by cilostazol. It is suggested that the action of cilostazol promoting cell survival is ascribed to the maxi-K channel opening-coupled up-regulation of CK2 phosphorylation and down-regulation of PTEN phosphorylation with resultant increased phosphorylation of Akt and CREB.

Apoptosis↗
PubMed2001

CD45 function is regulated by an acidic 19-amino acid insert in domain II that serves as a binding and phosphoacceptor site for casein kinase 2.

In this study experiments were conducted to elucidate the physical/functional relationship between CD45 and casein kinase 2 (CK2). Immunoprecipitation experiments demonstrated that CK2 associates with CD45 and that this interaction is inducible upon Ag receptor cross-linking in B and T cell lines as well as murine thymocytes and splenic B cells. However, yeast two-hybrid analysis failed to demonstrate a physical interaction between the individual CK2 alpha, alpha', or beta subunits and CD45. In contrast, a yeast three-hybrid assay in which either CK2 alpha and beta or alpha' and beta subunits were coexpressed with the cytoplasmic domain of CD45, demonstrated that both CK2 subunits are necessary for the interaction with CD45. Experiments using the yeast three-hybrid assay also revealed that a 19-aa acidic insert in domain II of CD45 mediates the physical interaction between CK2 and CD45. Structure/function experiments in which wild-type or mutant CD45RA and CD45RO isoforms were expressed in CD45-deficient Jurkat cells revealed that the 19-aa insert is important for optimal CD45 function. The ability of both CD45RA and CD45RO to reconstitute CD3-mediated signaling based on measurement of calcium mobilization and mitogen-activated protein kinase activation was significantly decreased by deletion of the 19-aa insert. Mutation of four serine residues within the 19-aa insert to alanine affected CD45 function to a similar extent compared with that of the deletion mutants. These findings support the hypothesis that a physical interaction between the CD45 cytoplasmic domain and CK2 is important for post-translational modification of CD45, which, in turn, regulates its catalytic function.

Animals↗
PubMed1994

Human larynx carcinoma cells resistant to cis-diamminedichloroplatinum(II): cross-resistance patterns.

In our previous study we developed two lines of human larynx carcinoma HEp2 cells resistant to cis-diamminedichloroplatinum(II) (CDDP) due to acute (CA3 cells), or continuous (CK2 cells) treatments with increased CDDP concentrations. CA3 line was 2.3-fold resistant, and CK2 line 3.7-fold resistant to CDDP as compared to the parental cells. In this study the sensitivity of CDDP resistant and parental cells to several antitumor drugs was examined using clonogenic survival assay. CK2 cells were 1.7-fold more resistant to vincristine than parental cells, while CA3 cells exhibited resistance to vincristine only at higher concentrations of this drug. Verapamil, an inhibitor of P-glycoprotein, was not able to reverse the resistance of CK2 cells to vincristine, indicating that this cross-resistance did not involve P-glycoprotein. As compared to the parental cells, CK2 cells were 2.1-fold resistant, and CA3 cells 1.7-fold resistant to mitomycin C. CK2 cells were 2-fold more resistant to 5-fluorouracil than the parental cells, while CA3 cells did not exhibit any change in the sensitivity to this drug. CA3 cells were 0.4-fold sensitive to epoxide and 0.53-fold sensitive to doxorubicin, while CK2 cells had the same sensitivity to these drugs as the parental cells. Our results showed that treatment schedule determines the response of CDDP resistant human larynx carcinoma cells to additional drugs, suggesting the complexity of the judicious choice of the drugs in the combined modality treatments of cancer.

Antineoplastic Agents↗
PubMed1997

The beta CK2tes gene encodes the tissue-specific regulatory subunit of casein kinase 2 in Drosophila melanogaster.

The beta CK2tes gene encodes a new variant of the tissue-specific regulatory beta-subunit of casein kinase 2 (CK2). The beta CK2tes open reading frame comprises nucleotide stretches encoding for the conservative polypeptide motifs characteristic for the CK2 beta-subunit including the Glu/Asp rich region responsible for regulation of CK2, C-terminal fragment responsible for binding to the catalytic alpha-subunit, and "zinc finger" motif. Unlike conserved sequences of CK2 beta-subunits in other organisms the beta CK2tes polypeptide has no autophosphorylation site or other putative phosphorylation sites. beta CK2tes is expressed only in testes, whereas beta CK2 expression is maximal at embryonic stages and is detected also in larvae. We suggest that beta CK2tes determines substrate specificity of CK2 and/or CK2 activity during spermatogenesis in Drosophila.

Amino Acid Sequence↗
PubMed2005

Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis.

Earlier studies in multiple epithelia have shown that cell-cell actin-based adherens junction (AJ) dynamics are regulated, at least in part, by the interplay of kinases and phosphatases that determines the intracellular phosphoprotein content. Yet it is virtually unknown regarding the role of protein kinases in Sertoli-germ cell AJ dynamics in the seminiferous epithelium of the testis. To address this issue, an in vitro coculture system utilizing Sertoli and germ cells was used to study the regulation of several protein kinases, including c-Src (the cellular form of the v-src transforming gene of Rous Sarcoma virus, RSV), carboxyl-terminal Src kinase (Csk), and casein kinase 2 (CK2), during AJ assembly. Both Sertoli and germ cells were shown to express c-Src, Csk, and CK2 with a relative Sertoli:germ cell ratio of approximately 1:1, suggesting both cell types contributed equally to the pool of these kinases in the epithelium. c-Src and Csk were shown to be stage-specific proteins during the epithelial cycle, being highest at stages VII-VIII. Studies using immunoprecipitation have illustrated that these kinases were structurally associated with the N-cadherin/beta-catenin, but not the nectin/afadin, protein complex, implicating that the cadherin/catenin protein complex is their likely putative substrate. An induction in c-Src, Csk, and CK2 were detected during Sertoli-germ cell AJ assembly in vitro but not when Sertoli cells were cultured alone. When adult rats were treated with 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364), a compound known to induce germ cell loss from the seminiferous epithelium, in particular elongating/elongate and round spermatids, by disrupting Sertoli-germ cell AJs, an induction of c-Src and Csk, but not CK2, was detected. Furthermore, a transient increase in the intrinsic kinase activities of c-Src, but not CK2, was also detected. This event was also associated with a loss of protein-protein association of N-cadherin and beta-catenin from the cadherin/catenin/c-Src/Csk/CK2 protein complex. Administration of PP1, a c-Src inhibitor, into adult rats via the jugular vein could induce the loss of spermatocytes and round spermatids, but not elongating/elongate spermatids, from the seminiferous epithelium. This result thus implicates the importance of c-Src in maintaining the integrity of AJs and possibly desmosome-like junctions between Sertoli cells and spermatocytes/round spermatids. In short, the data reported herein have shown that c-Src, Csk, and CK2 are novel protein kinases in AJ dynamics in the testis.

Adherens Junctions↗
PubMed2003

Pyrrolidine dithiocarbamate-induced neuronal cell death is mediated by Akt, casein kinase 2, c-Jun N-terminal kinase, and IkappaB kinase in embryonic hippocampal progenitor cells.

Pyrrolidine dithiocarbamate (PDTC) is known to induce cell death by the stimulation of intracellular zinc transport and subsequent modulation of nuclear factor-kappaB (NF-kappaB) activity. Zinc is a signaling messenger that is released by neuronal activity at many central excitatory synapses. Excessive synaptic release of zinc followed by entry into vulnerable neurons contributes to severe neuronal cell death. In the present study, we explored how PDTC modulates intracellular signal transduction pathways, leading to neuronal cell death. The exposure of immortalized embryonic hippocampal cells (H19-7) to PDTC within the range of 1-100 microM caused cell death in a dose-dependent manner. During the cell death, NF-kappaB activity increased in response to PDTC, and this activity corresponded well with the increase of intracellular free zinc levels, implying that the activation of NF-kappaB transmits the cell death signals of PDTC. Furthermore, PDTC caused the activation of IkappaB kinase (IKK), casein kinase 2 (CK2), phosphatidylinositol 3-kinase (PI-3K), and Akt, as well as mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 kinase. The blockade of PI-3K, JNK, and CK2 pathways resulted in a remarkable suppression of PDTC-induced cell death and also the activation of IKK, which subsequently led to a decrease of IkappaB phosphorylation. Although the overexpression of dominant-negative SEK in a transient manner did not inhibit the activation of Akt by PDTC, the transfection of kinase-inactive Akt mutants did cause a remarkable blockade of JNK activation, implying that Akt is present upstream of JNK in the PDTC-signaling pathways. Moreover, whereas selective CK2 inhibitors suppressed PDTC-induced JNK activation, the inhibition of JNK did not affect CK2 activity, suggesting that CK2 is directly related to the regulation of cell viability by PDTC and that the CK2-JNK pathway could be a downstream target of PDTC. Taken together, our results suggest that PDTC-mediated accumulation of intracellular zinc ions may affect cell viability by modulating several intracellular signaling pathways in neuronal hippocampal progenitor cells.

Animals↗
PubMed2005

A role for CK2alpha/beta in Xenopus early embryonic development.

CK2 is expressed widely in early embryonic development in several animal models, however its developmental role is unclear. One of the substrates of CK2 that is important in embryonic development is beta-catenin, the transcriptional co-activator of the canonical Wnt signaling pathway. This pathway has been implicated in diverse aspects of embryonic development, including one of the earliest events in embryonic development, the establishment of the dorso-ventral embryonic axis. In Xenopus laevis, dorso-ventral axis formation is dependent upon stabilization of beta-catenin in the future dorsal side of the embryo. Since CK2 phosphorylation of beta-catenin stabilizes it, we hypothesized that CK2 might be critical to upregulation of beta-catenin in Xenopus embryos and to the process of axis establishment. Our results demonstrate that CK2 is required for dorsal axis formation and is for normal upregulation of Wnt signaling genes and targets. Thus, CK2 is a regulator of endogenous axis formation in vertebrates.

Animals↗
PubMed1992

The consensus sequences for cdc2 kinase and for casein kinase-2 are mutually incompatible. A study with peptides derived from the beta-subunit of casein kinase-2.

Two series of synthetic peptides that reproduce the amino- and carboxyl-terminal segments of the beta-subunit of casein kinase-2, including the sites phosphorylated by CK2 and cdc2 kinase, respectively, have been used as model substrates for these enzymes. The N-terminal peptide beta(1-9), MSSSEEVSW, is readily phosphorylated by CK2 but not all by cdc2. The opposite is true of the C-terminal peptide beta(206-215), NFKSPVKTIR, whose Ser-4 is a good target for cdc2 while being unaffected by CK2. The individual substitutions of Pro-5 and Lys-7 in the latter peptide with Gly and Ala (or Glu), respectively, prevent its phosphorylation by cdc2, whereas the substitution of Lys-3 with Ala is well tolerated and the substitution of the target Ser with Thr actually improves phosphorylation. Thus the consensus sequence for cdc2 is shown to be X-S-P-X-K. Such a requirement for a basic residue at position +3 is opposite to that of CK2 whose consensus sequence (S-X-X-E/D/Yp/Sp) includes an acidic residue at the same position. Moreover the motif Ser-Pro is detrimental for CK2, preventing the phosphorylation of otherwise suitable peptides. These observations would rule out the possibility that the site specificity of CK2 might overlap with that of cdc2 and possibly of other Pro-directed protein kinases.

Amino Acid Sequence↗
PubMed2006

Purification and some properties of two creatine kinase isoforms from herring (Clupea harengus) spermatozoa.

Creatine kinase (CK, EC 2.7.3.2) isoforms play important role in energy homeostasis and together with easily diffusible compounds like creatine and phosphocreatine maintain a cellular energy buffer and intracellular energy transport system. The CK activity in spermatozoa is the highest from all studied tissues in herring. It was detected that the two CK isoforms, CK1 and CK2, are characteristic only for spermatozoa and are not expressed in other herring tissues. Isolation and purification procedures allowed obtaining purified enzymes with specific activity of the 345 micromol/min/mg for CK1 and 511 micromol/min/mg for CK2. Native Mr's of the CK1 and CK2 determined by gel permeation chromatography were about 330,000 and 90,000, respectively. These results indicate that CK1 form has octameric structure and CK2 is a dimer mostly characteristic for cytosolic CK enzymes. In immunoblotting studies with antisera against CK2, the response was observed for CK2 and there was no response for CK1 and two other isoforms from herring skeletal muscle. These findings make the herring isoforms an interesting model for studies on the fish CK biochemical properties.

Animals↗
PubMed2002

Mayaro virus infection cycle relies on casein kinase 2 activity.

Replication of Mayaro virus in Vero cells induces dramatic cytopathic effects and cell death. In this study, we have evaluated the role of casein kinase 2 (CK2) during Mayaro virus infection cycle. We found that CK2 was activated during the initial stages of infection ( approximately 36% after 4h). This activation was further confirmed when the enzyme was partially purified from the cellular lysate either by Mono Q 5/5Hr column or heparin-agarose column. Using this later column, we found that the elution profile of CK2 activity from infected cells was different from that obtained for control cell enzyme, suggesting a structural modification of CK2 after infection. Treatment of infected cells with a cell-permeable inhibitor of CK2, dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB), abolished the cytopathic effect in a dose-dependent manner. Together this set of data demonstrates for the first time that CK2 activity in host cells is required in Mayaro virus infection cycle.

Alphavirus↗
PubMed1996

Evidence that casein kinase 2 phosphorylates hepatic microsomal calcium-binding proteins 1 and 2 but not 3.

We have extensively purified three of the hepatic microsomal intralumenal Ca2+-binding proteins, CBP1, CBP2, and CBP3, which were originally described by Van et al. [(1989) J. Biol. Chem. 264, 17494-17501]. These apparently homogeneous preparations showed only single 45Ca2+ binding bands. On the basis of the peptide sequence, CBP2 was found to be highly homologous with the previously described protein ERp72. Similarly, CBP3 was identical to calreticulin and CBP1 had some homology to calmodulin. Contrary to the report of Van et al. (1989), we found that CBP2 had little thiol:protein disulfide oxidoreductase activity. Of the three purified preparations, only CBP2 exhibited apparent intrinsic protein kinase activity. This activity was found to be due to contamination of the CBP2 preparation by an extremely low concentration of tightly bound casein kinase 2 (CK2). In line with this observation, the phosphorylation was inhibited by heparin, removed by antibody to CK2, and stimulated by spermine. Furthermore, CBP2 was readily phosphorylated in vitro by added CK2 but only slowly phosphorylated by several other protein kinases. Thus, the persistence of CK2 in a highly purified preparation of CBP2 along with several other lines of evidence presented in this study might suggest that the protein CBP2 is a physiologically relevant substrate for CK2. Furthermore, these data suggest that CK2 might be localized in the lumen of the endoplasmic reticulum and that the phosphorylation of CBP2 in the lumen may play a role in the chaperone activity attributed to this protein.

Amino Acid Sequence↗
PubMed2002

Association and regulation of casein kinase 2 activity by adenomatous polyposis coli protein.

Mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis coli and also sporadic colorectal cancer development. By using antibodies raised against the N-terminal region of APC protein, we have detected the variable masses of endogenous APC proteins in individual cell lines established from human colorectal carcinomas caused by nonsense mutations of the gene. Phosphorylation of immunoprecipitates of full-length and truncated APC were observed in in vitro kinase reaction, indicating association of APC with protein kinase activity. The kinase activity complexed with APC was sensitive to heparin and used GTP as phosphoryl donor, suggesting an involvement of casein kinase 2 (CK2). Both CK2alpha- and beta-subunits were found to associate with APC in immunoprecipitates as well as in pull-down assays, with preferential interaction of APC with tetrameric CK2 holoenzyme. In synchronized cell populations, the association of APC with CK2 was cell cycle dependent, with the highest association in G(2)/M. Unexpectedly, APC immunoprecipitates containing full-length APC protein inhibited CK2 in vitro, whereas immunoprecipitates of truncated APC had little effect. This was confirmed by using recombinant APC, and the inhibitory region was localized to the C terminus of APC between residues 2086 and 2394. Overexpression of this fragment in SW480 cells suppressed cell proliferation rates as well as tumorigenesis. These results demonstrate a previously uncharacterized functional interaction between the tumor suppressor protein APC and CK2 and suggest that growth-inhibitory effects of APC may be regulated by inhibition of CK2.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Phosphorylation of the human ubiquitin-conjugating enzyme, CDC34, by casein kinase 2.

The ubiquitin-conjugating enzyme, CDC34, has been implicated in the ubiquitination of a number of vertebrate substrates, including p27(Kip1), IkappaBalpha, Wee1, and MyoD. We show that mammalian CDC34 is a phosphoprotein that is phosphorylated in proliferating cells. By yeast two-hybrid screening, we identified the regulatory (beta) subunit of human casein kinase 2 (CK2) as a CDC34-interacting protein and show that human CDC34 interacts in vivo with CK2beta in transfected cells. CDC34 is specifically phosphorylated in vitro by recombinant CK2 and HeLa nuclear extract at five sites within the carboxyl-terminal 36 amino acids of CDC34. Importantly, this phosphorylation is inhibited by heparin, a substrate-specific inhibitor of CK2. We have also identified a kinase activity associated with CDC34 in proliferating cells, and we show that this kinase is sensitive to heparin and can utilize GTP, strongly suggesting it is CK2. Phosphorylation of CDC34 by the associated kinase maps predominantly to residues 203 and 222. Mutation of CDC34 at CK2-targeted residues, Ser-203, Ser-222, Ser-231, Thr-233, and Ser-236, abolishes the phosphorylation of CDC34 observed in vivo and markedly shifts nuclearly localized CDC34 to the cytoplasm. These results suggest a potential role for CK2-mediated phosphorylation in the regulation of CDC34 cell localization and function.

Amino Acid Sequence↗
PubMed2005

Casein kinase 2 during early embryonic development in silkworm Bombyx mori: cDNA sequence, gene expression, and enzyme activity.

To clarify the property of casein kinase 2 (CK2) during early embryonic development in the silkworm, we compared the phosphorylation activities of CK2 in non-diapause and diapause eggs until 60 h after oviposition. In nondiapause eggs, the phosphorylated signals were found at each stage and became progressively stronger through each stage. On the other hand, in diapause eggs, the strongest phosphorylated signals were found at approximately 12 to 24 h after oviposition and became progressively weaker through each stage. To clarify the control mechanism of these enzyme activities, we tried to clone cDNAs encoding alpha- and beta-subunit of CK2 and analyze the gene expressions. The deduced amino acid sequence of the isolated cDNAs comprised 342 and 220 residues, and these sequences showed 85-90% identities to the alpha- and beta-subunit of CK2 in Spodoptera frugiperda. RT-PCR indicated that these genes were expressed in nondiapause and diapause eggs. However, these genes expressions were not parallel with the changes in CK2 activity. These results suggest that the changes in CK2 activity are regulated mainly at the level of post-transcription during embryonic development in Bombyx mori.

Amino Acid Sequence↗
PubMed1999

The unique N terminus of herpes simplex virus type 1 ribonucleotide reductase large subunit is phosphorylated by casein kinase 2, which may have a homologue in Escherichia coli.

Studies were performed to determine if the unique N-terminal domain of the R1 subunit from herpes simplex virus (HSV) type 1 ribonucleotide reductase is a substrate for casein kinase 2 (CK2). Transphosphorylation assays demonstrated that R1 was highly phosphorylated by this enzyme with multiple phosphorylation sites mapped to the N terminus between residues 1 and 245. Immunoprecipitation pull-down assays using R1-specific antisera failed to demonstrate a stable interaction between R1 and CK2 but residual amounts of CK2 present after immunoprecipitation efficiently transphosphorylated R1. Activity assays with a peptide substrate identified CK2 in R1 immunoprecipitated from infected-cell extracts but did not detect activity in R1 proteins immunoprecipitated from bacterial extracts. However, Western blotting identified potential E. coli homologues of the CK2 alpha and beta subunits. These results support conclusions that the N-terminal domain of HSV R1 is not a protein kinase and that all previous results can be explained by contaminating kinases, principally CK2.

Autoradiography↗
PubMed2005

Variable phosphorylation states of pigment-epithelium-derived factor differentially regulate its function.

The pigment epithelium-derived factor (PEDF) belongs to the family of noninhibitory serpins. Although originally identified in the eye, PEDF is widely expressed in other body regions including the plasma. This factor can act either as a neurotrophic or as an antiangiogenic factor, and we previously showed that the 2 effects of PEDF are regulated through phosphorylation by PKA and CK2. Here, we studied the interplay between the PKA and CK2 phosphorylation of PEDF, and found that a PEDF mutant mimicking the CK2-phosphorylated PEDF cannot be phosphorylated by PKA, while the mutant mimicking the PKA-phosphorylated PEDF is a good CK2 substrate. Using triple mutants that mimic the PKA- and CK2-phosphorylated and nonphosphorylated PEDF, we found that PEDF can induce several distinct cellular activities dependent on its phosphorylation. The mutant mimicking the accumulative PKA plus CK2 phosphorylation exhibited the strongest antiangiogenic and neurotrophic activities, while the mutants mimicking the individual phosphorylation site mutants had either a reduced activity or only one of these activities. Thus, differential phosphorylation induces variable effects of PEDF, and therefore contributes to the complexity of PEDF action. It is likely that the triple phosphomimetic mutant can be used to generate effective antiangiogenic or neurotrophic drugs.

Angiogenesis Inhibitors↗
PubMed2004

The antiapoptotic protein ICBP90 is a target for protein kinase 2.

Protein kinase 2 (casein kinase 2 [CK2]) is a protein serine/threonine kinase involved in cell proliferation with an expression that is dysregulated in tumors. ICBP90, a transcription factor exhibiting antiapoptotic properties, has several putative CK2 phosphorylation sites. The aim of the present study was to investigate whether ICBP90 could behave as a CK2 substrate. We observed that ICBP90 was more efficiently phosphorylated by the free CK2a subunit than by the heterotetrameric CK2 (alpha(2), beta(2)). Our results suggest that CK2 is an important regulator of the transcriptional activity of ICBP90 and therefore of the antiapoptotic properties of ICBP90. We propose that the "ICBP90 family" members may be substrates for CK2.

Animals↗