Abstract
Treatment of Jurkat cells with specific inhibitors of protein kinase CK2 induces apoptosis. Here we provide evidence that the antiapoptotic effect of CK2 can be at least partially mediated by upregulation of the Akt/PKB pathway. Such a conclusion is based on the following observations: (1) inhibition of CK2 by cell treatment with two structurally unrelated CK2 inhibitors induces downregulation of Akt/PKB, as judged from decreased phosphorylation of its physiological targets, and immunoprecipitate kinase assay; (2) similar results are observed upon reduction of CK2 catalytic subunit by the RNA-interference technique; (3) Akt/PKB Ser129 is phosphorylated by CK2 in vitro and in vivo; (4) such a phosphorylation of activated Akt/PKB correlates with a further increase in catalytic activity. These data disclose an unanticipated mechanism by which constitutive phosphorylation by CK2 may be required for maximal activation of Akt/PKB.
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Abbreviations
- CK2:
-
casein kinase 2
- GSK3:
-
glycogen synthase kinase 3
- IQA:
-
5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid
- MALDI:
-
matrix-assisted laser desorbtion and ionization
- MS/MS:
-
tandem mass spectrometry
- PDK1:
-
3-phosphoinositide-dependent protein kinase-1
- PH:
-
pleckstrin homology
- PI3-kinase:
-
phosphatidylinositol 3-kinase
- PKB:
-
protein kinase B (Akt)
- PTEN:
-
phosphatase and tensin homolog deleted on chromosome ten
- RNAi:
-
RNA interference
- SGK:
-
serum- and glucocorticoid-induced kinase
- siRNA:
-
short interfering RNA
- TBB:
-
4,5,6,7-tetrabromobenzotriazole
- WB:
-
Western blot
- w.t.:
-
wild type
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Acknowledgements
We thank Sir Philip Cohen (University of Dundee, Scotland) for critical reading of the manuscript, Joseph Schoepfer (Novartis, Basel, Switzerland) for providing IQA, the protein production team of the Division of Signal Transduction Therapy at the University of Dundee, Scotland (coordinated by Hilary McLauchlan and James Hastie) for providing the active and inactive full-length Akt, Peter James for the availability of the Proteomic Facility at Wallemberg Laboratory II, Lund University (Sweden), Sonia Facchin (University of Padova, Italy) for providing piD261, Sandra Marmiroli (University of Modena e Reggio Emilia, Italy) for providing the cDNA for HA-tagged myrAkt1. This work was supported by grants from the Italian MIUR (PRIN 2003), AIRC, and European Commission (PRO-KINASERESEARCH 503467).
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Di Maira, G., Salvi, M., Arrigoni, G. et al. Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell Death Differ 12, 668–677 (2005). https://doi.org/10.1038/sj.cdd.4401604
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DOI: https://doi.org/10.1038/sj.cdd.4401604
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