Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Protein kinase CK2 interacts with the splicing factor hPrp3p

Oncogene volume 27, pages 2390–2400 (2008)Cite this article

Abstract

Numerous signalling pathways in cells are influenced by the ubiquitous Ser/Thr protein kinase CK2. Protein kinase CK2 is composed of two regulatory β-subunits and two catalytic α- or α′-subunits. Several of the known CK2 substrates are proteins known to regulate transcriptional events. Here, we describe that protein kinase CK2 interacts with the splicing factor hPrp3p, which is important for the assembly of the spliceosome. In a two-hybrid screen hPrp3p is exclusively bound to the catalytic α- or α′-subunits of CK2 but not to the regulatory β-subunit. The interaction was confirmed by coimmunoprecipitation experiments in vitro and in vivo. Moreover, both proteins colocalized in nuclear speckles which is typical for splicing factor compartments within the nucleus. Phosphorylation experiments revealed that hPrp3p is also a substrate of protein kinase CK2. The main phosphorylation site was mapped to C-terminal residues. In vitro and in vivo splicing assays showed that the splicing activity is significantly influenced by the CK2–hPrp3p interaction. Thus, these data showed that CK2 is involved in the regulation of RNA processing.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11

Similar content being viewed by others

References

  • Bosc DG, Graham KC, Saulnier RB, Zhang CJ, Prober D, Gietz RD et al. (2000). Identification and characterization of CKIP-1, a novel pleckstrin homology domain-containing protein that interacts with protein kinase CK2. J Biol Chem 275: 14295–14306.

    Article  CAS  Google Scholar 

  • Burnett G, Kennedy EP . (1954). The enzymatic phosphorylation of proteins. J Biol Chem 211: 969–980.

    CAS  PubMed  Google Scholar 

  • Cabrejos ME, Allende CC, Maldonado E . (2004). Effects of phosphorylation by protein kinase CK2 on the human basal components of the RNA polymerase II transcription machinery. J Cell Biochem 93: 2–10.

    Article  CAS  Google Scholar 

  • Chakarova CF, Hims MM, Bolz H, bu-Safieh L, Patel RJ, Papaioannou MG et al. (2002). Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. Hum Mol Genet 11: 87–92.

    Article  CAS  Google Scholar 

  • Faust M, Kartarius S, Schwindling SL, Montenarh M . (2002). Cyclin H is a new binding partner for protein kinase CK2. Biochem Biophys Res Commun 269: 6–12.

    Google Scholar 

  • Faust M, Schuster N, Montenarh M . (1999). Specific binding of protein kinase CK2 catalytic subunits to tubulin. FEBS Lett 462: 51–56.

    Article  CAS  Google Scholar 

  • Gonzalez-Santos JM, Wang A, Jones J, Ushida C, Liu J, Hu J . (2002). Central region of the human splicing factor Hprp3p interacts with Hprp4p. J Biol Chem 277: 23764–23772.

    Article  CAS  Google Scholar 

  • Götz C, Kartarius S, Schetting S, Montenarh M . (2005). Immunologically defined subclasses of the protein kinase CK2β-subunit in prostate carcinoma cell lines. Mol Cell Biochem 274: 181–187.

    Article  Google Scholar 

  • Grankowski N, Boldyreff B, Issinger O-G . (1991). Isolation and characterization of recombinant human casein kinase II subunits α and β from bacteria. Eur J Biochem 198: 25–30.

    Article  CAS  Google Scholar 

  • Guerra B, Götz C, Wagner P, Montenarh M, Issinger O-G . (1997). The carboxy terminus of p53 mimicks the polylysine effect of protein kinase CK2-catalyzed MDM2 phosphorylation. Oncogene 14: 2683–2688.

    Article  CAS  Google Scholar 

  • Guerra B, Niefind K, Pinna LA, Schomburg D, Issinger O-G . (1998). Expression, purification and crystallization of the catalytic subunit of protein kinase CK2 from Zea mays. Acta Crystallogr D54: 143–145.

    CAS  Google Scholar 

  • Guerra B, Siemer S, Boldyreff B, Issinger OG . (1999). Protein kinase CK2: evidence for a protein kinase CK2β subunit fraction, devoid of the catalytic CK2α subunit, in mouse brain and testicles. FEBS Lett 462: 353–357.

    Article  CAS  Google Scholar 

  • Jain N, Mahendran R, Philp R, Guy GR, Tan YH, Cao X . (1996). Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. J Biol Chem 271: 13530–13536.

    Article  CAS  Google Scholar 

  • Krempler A, Kartarius S, Günther J, Montenarh M . (2005). Cyclin H is targeted to the nucleus by C-terminal nuclear localization sequences. Cell Mol Life Sci 62: 1379–1387.

    Article  CAS  Google Scholar 

  • Kuenzel EA, Krebs EG . (1985). A synthetic peptide substrate specific for casein kinase II. Proc Natl Acad Sci USA 82: 737–741.

    Article  CAS  Google Scholar 

  • Li M, Strand D, Krehan A, Pyerin W, Heid H, Neumann B et al. (1999). Casein kinase 2 binds and phosphorylates the nucleosome assembly protein-1 (NAP1) in Drosophila melanogaster. J Mol Biol 293: 1067–1084.

    Article  CAS  Google Scholar 

  • Litchfield DW . (2003). Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 369: 1–15.

    Article  CAS  Google Scholar 

  • Liu S, Rauhut R, Vornlocher HP, Luhrmann R . (2006). The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP. RNA 12: 1418–1430.

    Article  CAS  Google Scholar 

  • Maita H, Kitaura H, Keen TJ, Inglehearn CF, Ariga H, Iguchi-Ariga SM . (2004). PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa, is a splicing factor. Exp Cell Res 300: 283–296.

    Article  CAS  Google Scholar 

  • Meggio F, Boldyreff B, Issinger O-G, Pinna LA . (1994). Casein kinase 2 down-regulation and activation by polybasic peptides are mediated by acidic residues in the 55–64 region of the beta-subunit. A study with calmodulin as phosphorylatable substrate. Biochemistry 33: 4336–4342.

    Article  CAS  Google Scholar 

  • Meggio F, Pinna LA . (2003). One-thousand-and-one substrates of protein kinase CK2? The FASEB Journal 17: 349–368.

    Article  CAS  Google Scholar 

  • Messenger MM, Saulnier RB, Gilchrist AD, Diamond P, Gorbsky GJ, Litchfield DW . (2002). Interactions between protein kinase CK2 and Pin1Evidence for phosphorylation-dependent interactions. J Biol Chem 277: 23054–23064.

    Article  CAS  Google Scholar 

  • Palancade B, Dubois MF, Bensaude O . (2002). FCP1 phosphorylation by casein kinase 2 enhances binding to TFIIF and RNA polymerase II carboxyl-terminal domain phosphatase activity. J Biol Chem 277: 36061–36067.

    Article  CAS  Google Scholar 

  • Payne JM, Laybourn PJ, Dahmus ME . (1989). The transition of RNA polymerase II from initiation to elongation is associated with phosphorylation of the carboxyl-terminal domain of subunit IIa. J Biol Chem 264: 19621–19629.

    CAS  PubMed  Google Scholar 

  • Penner CG, Wang ZL, Litchfield DW . (1997). Expression and localization of epitope-tagged protein kinase CK2. J Cell Biochem 64: 525–537.

    Article  CAS  Google Scholar 

  • Pinna LA . (2002). Protein kinase CK2: a challenge to canons. J Cell Sci 115: 3873–3878.

    Article  CAS  Google Scholar 

  • Proudfoot NJ, Furger A, Dye MJ . (2002). Integrating mRNA processing with transcription. Cell 108: 501–512.

    Article  CAS  Google Scholar 

  • Sarno S, Reddy H, Meggio F, Ruzzene M, Davies SP, Donella-Deana A et al. (2001). Selectivity of 4,5,6,7-tetrabromobenzotriazole, an ATP site-directed inhibitor of protein kinase CK2 (‘casein kinase-2’). FEBS Lett 496: 44–48.

    Article  CAS  Google Scholar 

  • Schneider E, Kartarius S, Schuster N, Montenarh M . (2002). The cyclin H/cdk7/Mat1 kinase activity is regulated by CK2 phosphorylation of cyclin H. Oncogene 21: 5031–5037.

    Article  CAS  Google Scholar 

  • Schneider HR, Issinger O-G . (1988). Nucleolin (C23), a physiological substrate for casein kinase II. Biochem Biophys Res Commun 156: 1390–1397.

    Article  CAS  Google Scholar 

  • Schuster N, Prowald A, Schneider E, Scheidtmann K-H, Montenarh M . (1999). Regulation of p53 mediated transactivation by the β- subunit of protein kinase CK2. FEBS Lett 447: 160–166.

    Article  CAS  Google Scholar 

  • Shi Y, Brown ED, Walsh CT . (1994). Expression of recombinant human casein kinase II and recombinant heat shock protein 90 in Escherichia coli and characterization of their interactions. Proc Natl Acad Sci USA 91: 2767–2771.

    Article  CAS  Google Scholar 

  • Stalter G, Siemer S, Becht E, Ziegler M, Remberger K, Issinger O-G . (1994). Asymmetric expression of protein kinase CK2 in human kidney tumors. Biochem Biophys Res Commun 202: 141–147.

    Article  CAS  Google Scholar 

  • Trembley JH, Hu DL, Slaughter CA, Lahti JM, Kidd VJ . (2003). Casein kinase 2 interacts with cyclin-dependent kinase 11 (CDK11) in vivo and phosphorylates both the RNA polymerase II carboxyl-terminal domain and CDK11 in vitro. J Biol Chem 278: 2265–2270.

    Article  CAS  Google Scholar 

  • Trembley JH, Tatsumi S, Sakashita E, Loyer P, Slaughter CA, Suzuki H et al. (2005). Activation of pre-mRNA splicing by human RNPS1 is regulated by CK2 phosphorylation. Mol Cell Biol 25: 1446–1457.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by HOMFOR B 2004/11 to CG. We thank David Litchfield for providing us with the kinase dead CK2 mutants and Prof Ariga, Hokkaido University, Sapporo, Japan for the E1A-construct. Proofreading of the manuscript by Mrs. Jane C Crofts was greatly appreciated.

Author information

Authors and Affiliations

  1. Universität des Saarlandes, Medizinische Biochemie und Molekularbiologie, Homburg, Germany

    S Lehnert, C Götz, S Kartarius, B Schäfer & M Montenarh

Authors
  1. S Lehnert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Götz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Kartarius
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Montenarh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Montenarh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lehnert, S., Götz, C., Kartarius, S. et al. Protein kinase CK2 interacts with the splicing factor hPrp3p. Oncogene 27, 2390–2400 (2008). https://doi.org/10.1038/sj.onc.1210882

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210882

Keywords

This article is cited by

Search

Advanced search

Quick links