Protein kinase CK2 phosphorylates and upregulates Akt/PKB

Cell Death Differ. 2005 Jun;12(6):668-77. doi: 10.1038/sj.cdd.4401604.

Abstract

Treatment of Jurkat cells with specific inhibitors of protein kinase CK2 induces apoptosis. Here we provide evidence that the anti-apoptotic 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / chemistry
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Catalytic Domain / drug effects
  • Cell Line
  • Down-Regulation / drug effects
  • Enzyme Induction
  • Humans
  • Molecular Sequence Data
  • Mutation / genetics
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • RNA Interference
  • Signal Transduction / drug effects
  • Up-Regulation*

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Phosphoserine
  • AKT1 protein, human
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt