Protein kinase CK2 phosphorylates and upregulates Akt/PKB.
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.
Di Maira
G
G
Venetian Institute of Molecular Medicine (VIMM), University of Padova, Padova, Italy.
Salvi
M
M
Arrigoni
G
G
Marin
O
O
Sarno
S
S
Brustolon
F
F
Pinna
L A
LA
Ruzzene
M
M
D000595:Amino Acid Sequence; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004790:Enzyme Induction; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D010768:Phosphoserine; C494918:AKT1 protein, human; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt