Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase.
Protein kinase CK2 has been implicated in the regulation of a wide range of proteins that are important in cell proliferation and differentiation. Here we demonstrate that the stress signaling agents anisomycin, arsenite, and tumor necrosis factor-alpha stimulate the specific enzyme activity of CK2 in the human cervical carcinoma HeLa cells by up to 8-fold, and this could be blocked by the p38 MAP kinase inhibitor SB203580. We show that p38alpha MAP kinase, in a phosphorylation-dependent manner, can directly interact with the alpha and beta subunits of CK2 to activate the holoenzyme through what appears to be an allosteric mechanism. Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities.
Sayed
M
M
Department of Medicine, Koerner Pavilion, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Kim
S O
SO
Salh
B S
BS
Issinger
O G
OG
Pelech
S L
SL
D000595:Amino Acid Sequence; D000841:Anisomycin / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology*; D047390:Casein Kinase II; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D018053:Arsenites; D007093:Imidazoles; D011725:Pyridines; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000841:Anisomycin; D005982:Glutathione Transferase; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C015001:arsenite; C093642:SB 203580