Protein kinase CK2 subunits are positive regulators of AKT kinase.
Protein kinase CK2 is a highly conserved serine/threonine kinase ubiquitously distributed in all investigated eukaryotes and involved in several intracellular pathways which control, among others, cell cycle, proliferation, apoptosis and transformation. Similarly, the PI3K-AKT pathway deregulation has been shown to play an important role in tumor development and tumor response to anti-cancer treatment. In this study, it is shown that the specific inhibition of the PI3K-AKT signaling pathway in combination with depletion of CK2 subunits by antisense oligodeoxynucleotides leads to an enhanced drug-induced apoptotic response. Moreover, in vitro as well as in vivo studies show that the individual CK2 subunits interact with AKT kinase and that the complex formation is not modulated by the phosphorylation status of AKT. Furthermore, the fact that the interaction between CK2 subunits and AKT enhances AKT kinase activity identifies a novel molecular mechanism that leads to modulation of AKT activation raising the possibility that CK2 and AKT might be implicated in common pathways that control cell proliferation and survival.
Guerra
Barbara
B
Institute for Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark. bag@bmb.sdu.dk
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019556:COS Cells; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D020014:K562 Cells; D015739:Nocodazole / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D007334:Insulin-Like Growth Factor I; D047390:Casein Kinase II; D051057:Proto-Oncogene Proteins c-akt; D015739:Nocodazole; D000077191:Wortmannin